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Bouteldja A, Marceau L, Srivastava L, Cermakian N. Early-Life Ventral Hippocampal Lesion and Circadian Disruption Result in Altered Behavior in Adult Mice in a Sex-Dependent Manner. Eur J Neurosci 2025; 61:e70134. [PMID: 40356274 PMCID: PMC12069966 DOI: 10.1111/ejn.70134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2025] [Revised: 04/23/2025] [Accepted: 04/26/2025] [Indexed: 05/15/2025]
Abstract
Schizophrenia is believed to arise because of the interaction of early abnormal neurodevelopment with environmental insults during key developmental stages later in life. Furthermore, disrupted circadian rhythms are reported in patients, and circadian disruption is associated with increased symptom severity, hinting at its role as a risk factor. Using the neonatal ventral hippocampal lesion mouse model, we aimed to assess the interaction between disrupted ventral hippocampal development with circadian disruption during adolescence in affecting behavior in male and female C57BL/6N mice. After conducting a series of behavioral tests, we found that the neonatal ventral hippocampal lesion and chronic jet lag during adolescence synergistically led to increased anxiety-like behavior in males. In females, the lesion prevented increased social preference caused by chronic jet lag and led to increased anxiety-like behavior. Mice were then moved to running wheel cages to measure their locomotor activity rhythms. We found that the lesioned male mice exposed to chronic jet lag exhibited fragmented rhythms under constant darkness. Moreover, lesioned male and female mice, especially those exposed to chronic jet lag, had reduced activity counts under constant light. These findings highlight that the interaction of abnormal neurodevelopment in areas relevant to schizophrenia with circadian disruption during adolescence results in lasting behavioral changes in a sex-dependent manner in mice.
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Affiliation(s)
- Ahmed A. Bouteldja
- Douglas Mental Health University InstituteMontréalQuébecCanada
- Integrated Program in NeuroscienceMcGill UniversityMontréalQuébecCanada
| | | | - Lalit K. Srivastava
- Douglas Mental Health University InstituteMontréalQuébecCanada
- Department of PsychiatryMcGill UniversityMontréalQuébecCanada
| | - Nicolas Cermakian
- Douglas Mental Health University InstituteMontréalQuébecCanada
- Department of PsychiatryMcGill UniversityMontréalQuébecCanada
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Nenadić I, Falkenberg I, Mehl S, Kircher T. [Long-term courses in schizophrenia : A review of current results and developments]. DER NERVENARZT 2025; 96:5-14. [PMID: 39699660 PMCID: PMC11772515 DOI: 10.1007/s00115-024-01790-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 11/28/2024] [Indexed: 12/20/2024]
Abstract
Despite classical conceptions of schizophrenia as a progressive illness with a high chronification, current long-term follow-up studies show a higher proportion of remission, possibly also a higher proportion of recovery than previously assumed. The heterogeneity of clinical courses is also reflected in different trajectories of cognitive and biological (e.g., imaging) variables, in which many of those affected show remission. Early clinical intervention during the first weeks and months following the onset of psychosis are decisive not only for early remission but also possibly for the long-term outcome. The treatment and reduction of somatic comorbidities are promising approaches in addition to a differentiated core treatment to positively influence the course of the illness even years after the disease. The identification of additional predictors, e.g., based on biological parameters, can together with machine learning approaches contribute to optimization of an individualized core treatment.
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Affiliation(s)
- Igor Nenadić
- Klinik für Psychiatrie und Psychotherapie, Philipps Universität Marburg & Universitätsklinikum Gießen und Marburg (UKGM), Rudolf-Bultmann-Straße 8, 35039, Marburg, Deutschland.
| | - Irina Falkenberg
- Klinik für Psychiatrie und Psychotherapie, Philipps Universität Marburg & Universitätsklinikum Gießen und Marburg (UKGM), Rudolf-Bultmann-Straße 8, 35039, Marburg, Deutschland
| | - Stephanie Mehl
- Klinik für Psychiatrie und Psychotherapie, Philipps Universität Marburg & Universitätsklinikum Gießen und Marburg (UKGM), Rudolf-Bultmann-Straße 8, 35039, Marburg, Deutschland
| | - Tilo Kircher
- Klinik für Psychiatrie und Psychotherapie, Philipps Universität Marburg & Universitätsklinikum Gießen und Marburg (UKGM), Rudolf-Bultmann-Straße 8, 35039, Marburg, Deutschland
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3
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Kim HK, Voineskos AN, Neufeld NH, Alexopoulos GS, Bingham KS, Flint AJ, Marino P, Rothschild AJ, Whyte EM, Mulsant BH. Effect of olanzapine exposure on relapse and brain structure in patients with major depressive disorder with psychotic features. Mol Psychiatry 2024; 29:2459-2466. [PMID: 38503927 DOI: 10.1038/s41380-024-02523-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 02/21/2024] [Accepted: 03/07/2024] [Indexed: 03/21/2024]
Abstract
Some data suggest that antipsychotics may adversely affect brain structure. We examined the relationship among olanzapine exposure, relapse, and changes in brain structure in patients with major depressive disorder with psychotic features. We analyzed data from the Study of the Pharmacotherapy of Psychotic Depression II trial (STOP-PD II), a randomized, placebo-controlled trial in patients with psychotic depression who attained remission on sertraline and olanzapine and were randomized to continue sertraline plus olanzapine or placebo for 36 weeks. Olanzapine steady state concentration (SSC) were calculated based on sparsely-sampled levels. Rates of relapse and changes in brain structure were assessed as outcomes. There were significant associations between dosage and relapse rates (N = 118; HR = 0.94, 95% CI [0.897, 0.977], p = 0.002) or changes in left cortical thickness (N = 44; B = -2.0 × 10-3, 95% CI [-3.1 × 10-3, -9.6 × 10-4], p < 0.001) and between SSC and changes in left cortical thickness (N = 44; B = -8.7 × 10-4, 95% CI [-1.4 × 10-3, -3.6 × 10-4], p = 0.001). Similar results were found for the right cortex. These associations were no longer significant when the analysis was restricted to participants treated with olanzapine. Our findings suggest that, within its therapeutic range, the effect of olanzapine on relapse or cortical thickness does not depend on its dosage or SSC. Further research is needed on the effect of olanzapine and other antipsychotics on mood symptoms and brain structure.
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Affiliation(s)
- Helena K Kim
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Aristotle N Voineskos
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Nicholas H Neufeld
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - George S Alexopoulos
- Department of Psychiatry, Weill Cornell Medicine of Cornell University and New York Presbyterian Hospital, Westchester Division, New York, NY, USA
| | - Kathleen S Bingham
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Centre for Mental Health, University Health Network, Toronto, ON, Canada
| | - Alastair J Flint
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Centre for Mental Health, University Health Network, Toronto, ON, Canada
| | - Patricia Marino
- Department of Psychiatry, Weill Cornell Medicine of Cornell University and New York Presbyterian Hospital, Westchester Division, New York, NY, USA
| | - Anthony J Rothschild
- University of Massachusetts Chan Medical School and UMass Memorial Health Care, Worcester, MA, USA
| | - Ellen M Whyte
- Department of Psychiatry, University of Pittsburgh School of Medicine and UPMC Western Psychiatric Hospital, Pittsburgh, PA, USA
| | - Benoit H Mulsant
- Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
- Centre for Addiction and Mental Health, Toronto, ON, Canada.
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Ren H, Li J, Zhou J, Chen X, Tang J, Li Z, Wang Q. Grey matter volume reduction in the frontotemporal cortex associated with persistent verbal auditory hallucinations in Chinese patients with chronic schizophrenia: Insights from a 3 T magnetic resonance imaging study. Schizophr Res 2024; 269:123-129. [PMID: 38772324 DOI: 10.1016/j.schres.2024.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 04/03/2024] [Accepted: 05/13/2024] [Indexed: 05/23/2024]
Abstract
BACKGROUND Persistent auditory verbal hallucinations (pAVHs) are a fundamental manifestation of schizophrenia (SCZ), yet the exact connection between pAVHs and brain structure remains contentious. This study aims to explore the potential correlation between pAVHs and alterations in grey matter volume (GMV) within specific brain regions among individuals diagnosed with SCZ. METHODS 76 SCZ patients with pAVHs (pAVH group), 57 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were investigated using 3 T magnetic resonance imaging. The P3 hallucination item of the Positive and Negative Syndrome Scale was used to assess the severity of pAVHs. Voxel-based morphometry was used to analyze the GMV profile between the three groups. RESULTS Compared to the non-AVH and HC groups, the pAVH group exhibited extensive reduction in GMV within the frontotemporal cortex. Conversely, no significant difference in GMV was observed between the non-AVH and HC groups. The severity of pAVHs showed a negative correlation with GMV in several regions, including the right fusiform, right inferior temporal, right medial orbitofrontal, right superior frontal, and right temporal pole (p = 0.0036, Bonferroni correction). Stepwise linear regression analysis revealed that GMV in the right temporal pole (β = -0.29, p = 0.001) and right fusiform (β = -0.21, p = 0.01) were significantly associated with the severity of pAVHs. CONCLUSIONS Widespread reduction in GMV is observed within the frontotemporal cortex, particularly involving the right temporal pole and right fusiform, which potentially contribute to the pathogenesis of pAVHs in individuals with chronic SCZ.
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Affiliation(s)
- Honghong Ren
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China; Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Jinguang Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Jun Zhou
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Xiaogang Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China
| | - Jinsong Tang
- Department of Psychiatry, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Zongchang Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
| | - Qianjin Wang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China; Department of Psychiatry, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.
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Salisbury DF, Wulf BM, Seebold D, Coffman BA, Curtis MT, Karim HT. Predicted Brain Age in First-Episode Psychosis: Association with Inexpressivity. Brain Sci 2024; 14:532. [PMID: 38928532 PMCID: PMC11201938 DOI: 10.3390/brainsci14060532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/17/2024] [Accepted: 05/17/2024] [Indexed: 06/28/2024] Open
Abstract
Accelerated brain aging is a possible mechanism of pathology in schizophrenia. Advances in MRI-based brain development algorithms allow for the calculation of predicted brain age (PBA) for individuals. Here, we assessed PBA in 70 first-episode schizophrenia-spectrum individuals (FESz) and 76 matched healthy neurotypical comparison individuals (HC) to determine if FESz showed advanced aging proximal to psychosis onset and whether PBA was associated with neurocognitive, social functioning, or symptom severity measures. PBA was calculated with BrainAgeR (v2.1) from T1-weighted MR scans. There were no differences in the PBAs between groups. After controlling for actual age, a "younger" PBA was associated with higher vocabulary scores among all individuals, while an "older" PBA was associated with more severe negative symptom "Inexpressivity" component scores among FESz. Female participants in both groups had an elevated PBA relative to male participants. These results suggest that a relatively younger brain age is associated with a better semantic memory performance. There is no evidence for accelerated aging in FESz with a late adolescent/early adult onset. Despite a normative PBA, FESz with a greater residual PBA showed impairments in a cluster of negative symptoms, which may indicate some underlying age-related pathology proximal to psychosis onset. Although a period of accelerated aging cannot be ruled out with disease course, it does not occur at the time of the first episode.
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Affiliation(s)
- Dean F. Salisbury
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Brian M. Wulf
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Dylan Seebold
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Brian A. Coffman
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Mark T. Curtis
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Helmet T. Karim
- Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15260, USA
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Garcia-Marti G, Escarti MJ, Nacher J, Perez-Rando M, Mane A, Usall J, Berrocoso E, Pomarol-Clotet E, Lopez-Ilundain JM, Cuesta MJ, Rodriguez-Jimenez R, Gonzalez-Pinto A, Mar L, Ibañez A, Roldan A, Janssen J, Parellada M, Amoretti S, Bernardo M, Sanjuan J, Aguilar EJ. Progressive loss of cortical gray matter in first episode psychosis patients with auditory hallucinations. Schizophr Res 2024; 267:534-545. [PMID: 38044223 DOI: 10.1016/j.schres.2023.11.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 09/18/2023] [Accepted: 11/26/2023] [Indexed: 12/05/2023]
Abstract
BACKGROUND Previous longitudinal magnetic resonance imaging studies have shown progressive gray matter (GM) reduction during the earliest phases of schizophrenia. It is unknown whether these progressive processes are homogeneous in all groups of patients. One way to obtain more valid findings is to focus on the symptoms. Auditory hallucinations (AHs) are frequent and reliable symptoms of psychosis. The present study aims to analyze whether longitudinal changes in structural abnormalities in cortical regions are related to the presence of AHs and the intensity of psychotic symptoms in a large sample. METHODS A Magnetic Resonance (MR) voxel-based morphometry analysis was applied to a group of 128 first episodes psychosis (FEP) patients (63 patients with AHs and 65 patients without AHs) and 78 matched healthy controls at baseline and at a 2-year follow-up. RESULTS At baseline, FEP patients exhibited significant GM volume reductions in the temporal, frontal and precentral regions. At follow-up, FEP patients exhibited GM volume changes in the temporal, Rolandic, frontal, precentral and insula regions. At baseline, no significant differences were found between FEP patients with and without AHs. At follow-up, while FEP patients with AHs showed less GM volume in temporal and frontal lobes, non-AH FEP patients showed reductions in the frontal, precentral and fusiform areas. PANSS scores showed statistically significant correlations with GM volume reductions at baseline and follow-up. CONCLUSIONS Brain cortical loss in the early phases of psychosis is not associated with potentially transitory AHs; however, brain structural changes may emerge as AHs appear in chronic patients.
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Affiliation(s)
- Gracian Garcia-Marti
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Biomedical Engineering Unit / Radiology Department, Quirónsalud Hospital, Valencia, Spain; Institute of research of the Clinic Hospital from Valencia (INCLIVA), Valencia, Spain.
| | - Maria J Escarti
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Institute of research of the Clinic Hospital from Valencia (INCLIVA), Valencia, Spain; Unit of Psychiatry, Clinic Hospital Valencia, University of Valencia, Valencia, Spain
| | - Juan Nacher
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Institute of research of the Clinic Hospital from Valencia (INCLIVA), Valencia, Spain; Institute of Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Burjassot, Spain
| | - Marta Perez-Rando
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Institute of research of the Clinic Hospital from Valencia (INCLIVA), Valencia, Spain; Institute of Biotechnology and Biomedicine (BIOTECMED), Universitat de València, Burjassot, Spain
| | - Anna Mane
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Institut de Neuropsiquiatria i Adiccions (INAD), Parc de Salut Mar, Barcelona, Spain; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain; Department of Medicine and Life Sciences (MELIS). Universitat Pompeu Fabra, Barcelona, Spain
| | - Judith Usall
- Institut de Recerca Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain; Parc Sanitari Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain
| | - Esther Berrocoso
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Neuropsychopharmacology and Psychobiology Research Group, Department of Neuroscience, Faculty of Medicine, University of Cádiz, Cádiz, Spain; Instituto de Investigación e Innovación Biomédica de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain
| | - Edith Pomarol-Clotet
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain
| | - Jose M Lopez-Ilundain
- Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNa), Pamplona, Spain
| | - Manuel J Cuesta
- Department of Psychiatry, Hospital Universitario de Navarra, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNa), Pamplona, Spain
| | - Roberto Rodriguez-Jimenez
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain; Universidad Complutense de Madrid (UCM), Madrid, Spain
| | - Ana Gonzalez-Pinto
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Bioaraba, Department of Psychiatry, Hospital Universitario de Alava, UPV/EHU, Vitoria, Spain
| | - Lorea Mar
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Bioaraba, Department of Psychiatry, Hospital Universitario de Alava, UPV/EHU, Vitoria, Spain
| | - Angela Ibañez
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Psychiatry, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain
| | - Alexandra Roldan
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Psychiatry Department, Hospital de la Santa Creu i Sant Pau, IIB SANT PAU, Barcelona, Spain
| | - Joost Janssen
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain
| | - Mara Parellada
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain; School of Medicine, Universidad Complutense, Madrid, Spain
| | - Silvia Amoretti
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Barcelona Clínic Schizophrenia Unit, Neuroscience Institute, Hospital Clínic of Barcelona; University of Barcelona, Spain; Bipolar and Depressive Disorder Unit, Neuroscience Institute, Hospital Clínic, Barcelona, Spain; Group of Psychiatry, Mental Health and Addictions, Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
| | - Miquel Bernardo
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Barcelona Clínic Schizophrenia Unit (BCSU), Neuroscience Institute, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Julio Sanjuan
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Institute of research of the Clinic Hospital from Valencia (INCLIVA), Valencia, Spain; Unit of Psychiatry, Clinic Hospital Valencia, University of Valencia, Valencia, Spain
| | - Eduardo J Aguilar
- Biomedical Research Networking Centre in Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Institute of research of the Clinic Hospital from Valencia (INCLIVA), Valencia, Spain; Unit of Psychiatry, Clinic Hospital Valencia, University of Valencia, Valencia, Spain
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Shi H, Zhang Y, Yang Y, Zhang H, Li W, Zhong Z, Lv L. Serum S100B protein and white matter changes in schizophrenia before and after medication. Brain Res Bull 2024; 210:110927. [PMID: 38485004 DOI: 10.1016/j.brainresbull.2024.110927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 03/11/2024] [Indexed: 03/23/2024]
Abstract
Schizophrenia patients have abnormalities in white matter (WM) integrity in brain regions. S100B has been shown to be a marker protein for glial cells. The atypical antipsychotics have neuroprotective effects on the brain. It is not clear whether antipsychotics can induce S100B changes and improve symptoms by protecting oligodendrocytes. To investigate WM and S100B changes and associations and determine the effect of quetiapine on WM and S100B in schizophrenia patients, we determined serum S100B levels with solid phase immunochromatography and fractional anisotropy（FA）values of 36 patients and 40 healthy controls. Patients exhibited significantly higher serum concentrations of S100B and decreased FA values in left postcentral，right superior frontal，right thalamus, and left inferior occipital gyrus, while higher in right temporal cortex WM compared with healthy controls. Following treatment with quetiapine, patients had decreased S100B and higher FA values in right cerebellum，right superior frontal，right thalamus, and left parietal cortex，and decreased FA values in right temporal cortex WM compared with pre-treatment values. Furthermore, S100B were negatively correlated with PANSS positive scores and positively correlated with FA values in the left postcentral cortex. In addition，the percentage change in FA values in the right temporal cortex was positively correlated with the percentage change in the S100B, percentage reduction in PANSS scores, and percentage reduction in PANSS-positive scores. Our findings demonstrated abnormalities in S100B and WM microstructure in patients with schizophrenia. These abnormalities may be partly reversed by quetiapine treatment.
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Affiliation(s)
- Han Shi
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China
| | - Yan Zhang
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China
| | - Yongfeng Yang
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China
| | - Haisan Zhang
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Wenqiang Li
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China
| | - Zhaoxi Zhong
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China.
| | - Luxian Lv
- Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang, China; International Joint Research Laboratory for Psychiatry and Neuroscience of Henan, Xinxiang, China.
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Slováková A, Kúdelka J, Škoch A, Jakob L, Fialová M, Fürstová P, Bakštein E, Bankovská Motlová L, Knytl P, Španiel F. Time is the enemy: Negative symptoms are related to even slight differences in the duration of untreated psychosis. Compr Psychiatry 2024; 130:152450. [PMID: 38241816 DOI: 10.1016/j.comppsych.2024.152450] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Revised: 12/26/2023] [Accepted: 01/12/2024] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.
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Affiliation(s)
- Andrea Slováková
- National Institute of Mental Health, Klecany, Czech Republic; 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - Jan Kúdelka
- National Institute of Mental Health, Klecany, Czech Republic
| | - Antonín Škoch
- National Institute of Mental Health, Klecany, Czech Republic; Institute for Clinical and Experimental Medicine, Department of Diagnostic and Interventional Radiology, Prague, Czech Republic.
| | - Lea Jakob
- National Institute of Mental Health, Klecany, Czech Republic.
| | - Markéta Fialová
- National Institute of Mental Health, Klecany, Czech Republic; 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - Petra Fürstová
- National Institute of Mental Health, Klecany, Czech Republic.
| | - Eduard Bakštein
- National Institute of Mental Health, Klecany, Czech Republic.
| | | | - Pavel Knytl
- National Institute of Mental Health, Klecany, Czech Republic.
| | - Filip Španiel
- National Institute of Mental Health, Klecany, Czech Republic; 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
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9
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Lan H, Suo X, Zuo C, Ni W, Wang S, Kemp GJ, Gong Q. Shared and distinct abnormalities of brain magnetization transfer ratio in schizophrenia and major depressive disorder: a comparative voxel-based meta-analysis. Chin Med J (Engl) 2023; 136:2824-2833. [PMID: 37697951 PMCID: PMC10686600 DOI: 10.1097/cm9.0000000000002538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Indexed: 09/13/2023] Open
Abstract
BACKGROUND Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR). METHODS A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics. RESULTS A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum ( P =0.0006) and left fusiform gyrus ( P =0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group. CONCLUSIONS The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.
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Affiliation(s)
- Huan Lan
- Department of Radiology, Huaxi MR Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Xueling Suo
- Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian 361000, China
| | - Chao Zuo
- Department of Radiology, Huaxi MR Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan 610041, China
| | - Weishi Ni
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China
| | - Song Wang
- Department of Radiology, Huaxi MR Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
- Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
| | - Graham J. Kemp
- Liverpool Magnetic Resonance Imaging Centre (LiMRIC) and Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L693BX, United Kingdom
| | - Qiyong Gong
- Department of Radiology, Huaxi MR Research Center (HMRRC), West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
- Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian 361000, China
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10
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Agarwal SM, Dissanayake J, Agid O, Bowie C, Brierley N, Chintoh A, De Luca V, Diaconescu A, Gerretsen P, Graff-Guerrero A, Hawco C, Herman Y, Hill S, Hum K, Husain MO, Kennedy JL, Kiang M, Kidd S, Kozloff N, Maslej M, Mueller DJ, Naeem F, Neufeld N, Remington G, Rotenberg M, Selby P, Siddiqui I, Szacun-Shimizu K, Tiwari AK, Thirunavukkarasu S, Wang W, Yu J, Zai CC, Zipursky R, Hahn M, Foussias G. Characterization and prediction of individual functional outcome trajectories in schizophrenia spectrum disorders (PREDICTS study): Study protocol. PLoS One 2023; 18:e0288354. [PMID: 37733693 PMCID: PMC10513234 DOI: 10.1371/journal.pone.0288354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 06/23/2023] [Indexed: 09/23/2023] Open
Abstract
Schizophrenia spectrum disorders (SSDs) are associated with significant functional impairments, disability, and low rates of personal recovery, along with tremendous economic costs linked primarily to lost productivity and premature mortality. Efforts to delineate the contributors to disability in SSDs have highlighted prominent roles for a diverse range of symptoms, physical health conditions, substance use disorders, neurobiological changes, and social factors. These findings have provided valuable advances in knowledge and helped define broad patterns of illness and outcomes across SSDs. Unsurprisingly, there have also been conflicting findings for many of these determinants that reflect the heterogeneous population of individuals with SSDs and the challenges of conceptualizing and treating SSDs as a unitary categorical construct. Presently it is not possible to identify the functional course on an individual level that would enable a personalized approach to treatment to alter the individual's functional trajectory and mitigate the ensuing disability they would otherwise experience. To address this ongoing challenge, this study aims to conduct a longitudinal multimodal investigation of a large cohort of individuals with SSDs in order to establish discrete trajectories of personal recovery, disability, and community functioning, as well as the antecedents and predictors of these trajectories. This investigation will also provide the foundation for the co-design and testing of personalized interventions that alter these functional trajectories and improve outcomes for people with SSDs.
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Affiliation(s)
- Sri Mahavir Agarwal
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
- Temerty Faculty Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Psychiatry, University of Toronto, Toronto, Canada
- Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada
| | - Joel Dissanayake
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Ofer Agid
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Christopher Bowie
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Noah Brierley
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Araba Chintoh
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Vincenzo De Luca
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Andreea Diaconescu
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Philip Gerretsen
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Ariel Graff-Guerrero
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Colin Hawco
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Yarissa Herman
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Sean Hill
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Kathryn Hum
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Muhammad Omair Husain
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - James L. Kennedy
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Michael Kiang
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Sean Kidd
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Nicole Kozloff
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Marta Maslej
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Daniel J. Mueller
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Farooq Naeem
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Nicholas Neufeld
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Gary Remington
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Martin Rotenberg
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Peter Selby
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Ishraq Siddiqui
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Kate Szacun-Shimizu
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Arun K. Tiwari
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | | | - Wei Wang
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Joanna Yu
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Clement C. Zai
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Robert Zipursky
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
| | - Margaret Hahn
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
- Temerty Faculty Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Psychiatry, University of Toronto, Toronto, Canada
- Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada
| | - George Foussias
- Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada
- Temerty Faculty Institute of Medical Science, University of Toronto, Toronto, Canada
- Department of Psychiatry, University of Toronto, Toronto, Canada
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11
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Hua JPY, Loewy RL, Stuart B, Fryer SL, Niendam TA, Carter CS, Vinogradov S, Mathalon DH. Cortical and subcortical brain morphometry abnormalities in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia. Psychiatry Res Neuroimaging 2023; 332:111653. [PMID: 37121090 PMCID: PMC10362971 DOI: 10.1016/j.pscychresns.2023.111653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 03/27/2023] [Accepted: 04/18/2023] [Indexed: 05/02/2023]
Abstract
Neuroimaging studies have documented morphometric brain abnormalities in schizophrenia, but less is known about them in individuals at clinical high-risk for psychosis (CHR-P), including how they compare with those observed in early schizophrenia (ESZ). Accordingly, we implemented multivariate profile analysis of regional morphometric profiles in CHR-P (n = 89), ESZ (n = 93) and healthy controls (HC; n = 122). ESZ profiles differed from HC and CHR-P profiles, including 1) cortical thickness: significant level reduction and regional non-parallelism reflecting widespread thinning, except for entorhinal and pericalcarine cortex, 2) basal ganglia volume: significant level increase and regional non-parallelism reflecting larger caudate and pallidum, and 3) ventricular volume: significant level increase with parallel regional profiles. CHR-P and ESZ cerebellar profiles showed significant non-parallelism with HC profiles. Regional profiles did not significantly differ between groups for cortical surface area or subcortical volume. Compared to CHR-P followed for ≥18 months without psychosis conversion (n = 31), CHR-P converters (n = 17) showed significant non-parallel ventricular volume expansion reflecting specific enlargement of lateral and inferolateral regions. Antipsychotic dosage in ESZ was significantly correlated with frontal cortical thinning. Results suggest that morphometric abnormalities in ESZ are not present in CHR-P, except for ventricular enlargement, which was evident in CHR-P who developed psychosis.
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Affiliation(s)
- Jessica P Y Hua
- Sierra Pacific Mental Illness Research Education and Clinical Centers, San Francisco VA Medical Center, and the University of California, San Francisco, CA, United States; Mental Health Service, San Francisco VA Medical Center, San Francisco, 94121, CA, United States; Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, 94143, CA, United States; Department of Psychological Sciences, University of Missouri, Columbia, 65211, MO, United States
| | - Rachel L Loewy
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, 94143, CA, United States
| | - Barbara Stuart
- Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, 94143, CA, United States
| | - Susanna L Fryer
- Mental Health Service, San Francisco VA Medical Center, San Francisco, 94121, CA, United States
| | - Tara A Niendam
- Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis, 95616, CA, United States
| | - Cameron S Carter
- Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis, 95616, CA, United States
| | - Sophia Vinogradov
- Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, 55455, MN, United States
| | - Daniel H Mathalon
- Mental Health Service, San Francisco VA Medical Center, San Francisco, 94121, CA, United States; Department of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, 94143, CA, United States.
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12
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Zhu Y, Webster MJ, Walker AK, Massa P, Middleton FA, Weickert CS. Increased prefrontal cortical cells positive for macrophage/microglial marker CD163 along blood vessels characterizes a neuropathology of neuroinflammatory schizophrenia. Brain Behav Immun 2023; 111:46-60. [PMID: 36972743 DOI: 10.1016/j.bbi.2023.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 03/01/2023] [Accepted: 03/23/2023] [Indexed: 03/29/2023] Open
Abstract
Transcript levels of cytokines and SERPINA3 have been used to define a substantial subset (40%) of individuals with schizophrenia with elevated inflammation and worse neuropathology in the dorsolateral prefrontal cortex (DLPFC). In this study, we tested if inflammatory proteins are likewise related to high and low inflammatory states in the human DLFPC in people with schizophrenia and controls. Levels of inflammatory cytokines (IL6, IL1β, IL18, IL8) and a macrophage marker (CD163 protein) were measured in brains obtained from the National Institute of Mental Health (NIMH) (N = 92). First, we tested for diagnostic differences in protein levels overall, then we determined the percentage of individuals that could be defined as "high" inflammation using protein levels. IL-18 was the only cytokine to show increased expression in schizophrenia compared to controls overall. Interestingly, two-step recursive clustering analysis showed that IL6, IL18, and CD163 protein levels could be used as predictors of "high and low" inflammatory subgroups. By this model, a significantly greater proportion of schizophrenia cases (18/32; 56.25%; SCZ) were identified as belonging to the high inflammatory (HI) subgroup compared to control cases (18/60; 30%; CTRL) [χ2(1) = 6.038, p = 0.014]. When comparing across inflammatory subgroups, IL6, IL1β, IL18, IL8, and CD163 protein levels were elevated in both SCZ-HI and CTRL-HI compared to both low inflammatory subgroups (all p < 0.05). Surprisingly, TNFα levels were significantly decreased (-32.2%) in schizophrenia compared to controls (p < 0.001), and were most diminished in the SCZ-HI subgroup compared to both CTRL-LI and CTRL-HI subgroups (p < 0.05). Next, we asked if the anatomical distribution and density of CD163+ macrophages differed in those with schizophrenia and high inflammation status. Macrophages were localized to perivascular sites and found surrounding small, medium and large blood vessels in both gray matter and white matter, with macrophage density highest at the pial surface in all schizophrenia cases examined. A higher density of CD163+ macrophages, that were also larger and more darkly stained, was found in the SCZ-HI subgroup (+154% p < 0.05). We also confirmed the rare existence of parenchymal CD163+ macrophages in both high inflammation subgroups (schizophrenia and controls). Brain CD163+ cell density around blood vessels positively correlated with CD163 protein levels. In conclusion, we find a link between elevated interleukin cytokine protein levels, decreased TNFα protein levels, and elevated CD163+ macrophage densities especially along small blood vessels in those with neuroinflammatory schizophrenia.
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Affiliation(s)
- Yunting Zhu
- Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA
| | | | - Adam K Walker
- School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; Laboratory of Immunopsychiatry, Neuroscience Research Australia, Sydney, NSW, Australia; Monash Institute of Pharmaceutical Science, Monash University, Parkville, Vic, Australia
| | - Paul Massa
- Department of Neurology, Upstate Medical University, Syracuse, NY 13210, USA; Department of Microbiology and Immunology, Upstate Medical University, Syracuse, NY 13210, USA
| | - Frank A Middleton
- Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA
| | - Cynthia Shannon Weickert
- Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, NY 13210, USA; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia.
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13
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Adamu MJ, Qiang L, Nyatega CO, Younis A, Kawuwa HB, Jabire AH, Saminu S. Unraveling the pathophysiology of schizophrenia: insights from structural magnetic resonance imaging studies. Front Psychiatry 2023; 14:1188603. [PMID: 37275974 PMCID: PMC10236951 DOI: 10.3389/fpsyt.2023.1188603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 04/20/2023] [Indexed: 06/07/2023] Open
Abstract
Background Schizophrenia affects about 1% of the global population. In addition to the complex etiology, linking this illness to genetic, environmental, and neurobiological factors, the dynamic experiences associated with this disease, such as experiences of delusions, hallucinations, disorganized thinking, and abnormal behaviors, limit neurological consensuses regarding mechanisms underlying this disease. Methods In this study, we recruited 72 patients with schizophrenia and 74 healthy individuals matched by age and sex to investigate the structural brain changes that may serve as prognostic biomarkers, indicating evidence of neural dysfunction underlying schizophrenia and subsequent cognitive and behavioral deficits. We used voxel-based morphometry (VBM) to determine these changes in the three tissue structures: the gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). For both image processing and statistical analysis, we used statistical parametric mapping (SPM). Results Our results show that patients with schizophrenia exhibited a significant volume reduction in both GM and WM. In particular, GM volume reductions were more evident in the frontal, temporal, limbic, and parietal lobe, similarly the WM volume reductions were predominantly in the frontal, temporal, and limbic lobe. In addition, patients with schizophrenia demonstrated a significant increase in the CSF volume in the left third and lateral ventricle regions. Conclusion This VBM study supports existing research showing that schizophrenia is associated with alterations in brain structure, including gray and white matter, and cerebrospinal fluid volume. These findings provide insights into the neurobiology of schizophrenia and may inform the development of more effective diagnostic and therapeutic approaches.
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Affiliation(s)
- Mohammed Jajere Adamu
- Department of Electronic Science and Technology, School of Microelectronics, Tianjin University, Tianjin, China
- Department of Computer Science, Yobe State University, Damaturu, Nigeria
| | - Li Qiang
- Department of Electronic Science and Technology, School of Microelectronics, Tianjin University, Tianjin, China
| | - Charles Okanda Nyatega
- Department of Information and Communication Engineering, School of Electrical and Information Engineering, Tianjin University, Tianjin, China
- Department of Electronics and Telecommunication Engineering, Mbeya University of Science and Technology, Mbeya, Tanzania
| | - Ayesha Younis
- Department of Electronic Science and Technology, School of Microelectronics, Tianjin University, Tianjin, China
| | - Halima Bello Kawuwa
- Department of Biomedical Engineering and Scientific Instruments, School of Precision Instruments and Optoelectronics Engineering, Tianjin University, Tianjin, China
| | - Adamu Halilu Jabire
- Department of Electrical and Electronics Engineering, Taraba State University, Jalingo, Nigeria
| | - Sani Saminu
- Department of Biomedical Engineering, University of Ilorin, Ilorin, Nigeria
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14
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Ferreira V, Folgueira C, García-Altares M, Guillén M, Ruíz-Rosario M, DiNunzio G, Garcia-Martinez I, Alen R, Bookmeyer C, Jones JG, Cigudosa JC, López-Larrubia P, Correig-Blanchar X, Davis RJ, Sabio G, Rada P, Valverde ÁM. Hypothalamic JNK1-hepatic fatty acid synthase axis mediates a metabolic rewiring that prevents hepatic steatosis in male mice treated with olanzapine via intraperitoneal: Additional effects of PTP1B inhibition. Redox Biol 2023; 63:102741. [PMID: 37230004 DOI: 10.1016/j.redox.2023.102741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 05/27/2023] Open
Abstract
Olanzapine (OLA), a widely used second-generation antipsychotic (SGA), causes weight gain and metabolic alterations when administered orally to patients. Recently, we demonstrated that, contrarily to the oral treatment which induces weight gain, OLA administered via intraperitoneal (i.p.) in male mice resulted in body weight loss. This protection was due to an increase in energy expenditure (EE) through a mechanism involving the modulation of hypothalamic AMPK activation by higher OLA levels reaching this brain region compared to those of the oral treatment. Since clinical studies have shown hepatic steatosis upon chronic treatment with OLA, herein we further investigated the role of the hypothalamus-liver interactome upon OLA administration in wild-type (WT) and protein tyrosine phosphatase 1B knockout (PTP1B-KO) mice, a preclinical model protected against metabolic syndrome. WT and PTP1B-KO male mice were fed an OLA-supplemented diet or treated via i.p. Mechanistically, we found that OLA i.p. treatment induces mild oxidative stress and inflammation in the hypothalamus in a JNK1-independent and dependent manner, respectively, without features of cell dead. Hypothalamic JNK activation up-regulated lipogenic gene expression in the liver though the vagus nerve. This effect concurred with an unexpected metabolic rewiring in the liver in which ATP depletion resulted in increased AMPK/ACC phosphorylation. This starvation-like signature prevented steatosis. By contrast, intrahepatic lipid accumulation was observed in WT mice treated orally with OLA; this effect being absent in PTP1B-KO mice. We also demonstrated an additional benefit of PTP1B inhibition against hypothalamic JNK activation, oxidative stress and inflammation induced by chronic OLA i.p. treatment, thereby preventing hepatic lipogenesis. The protection conferred by PTP1B deficiency against hepatic steatosis in the oral OLA treatment or against oxidative stress and neuroinflammation in the i.p. treatment strongly suggests that targeting PTP1B might be also a therapeutic strategy to prevent metabolic comorbidities in patients under OLA treatment in a personalized manner.
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Affiliation(s)
- Vitor Ferreira
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain
| | - Cintia Folgueira
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid, Spain
| | - María García-Altares
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain; Rovira I Virgili University, Department of Electronic Engineering, Tarragona, Spain
| | - Maria Guillén
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain
| | | | - Giada DiNunzio
- Center for Neurosciences and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal
| | - Irma Garcia-Martinez
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain
| | - Rosa Alen
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain
| | - Christoph Bookmeyer
- Rovira I Virgili University, Department of Electronic Engineering, Tarragona, Spain
| | - John G Jones
- Center for Neurosciences and Cell Biology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal
| | | | - Pilar López-Larrubia
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain
| | - Xavier Correig-Blanchar
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain; Rovira I Virgili University, Department of Electronic Engineering, Tarragona, Spain; Institut D'Investigacio Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Roger J Davis
- Program in Molecular Medicine, Chan Medical School, University of Massachusetts, Worcester, USA
| | - Guadalupe Sabio
- Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029, Madrid, Spain
| | - Patricia Rada
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain.
| | - Ángela M Valverde
- Instituto de Investigaciones Biomedicas Alberto Sols (IIBM), CSIC-UAM, Madrid, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Spain.
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15
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Tishler TA, Ellingson BM, Salvadore G, Baker P, Turkoz I, Subotnik KL, de la Fuente-Sandoval C, Nuechterlein KH, Alphs L. Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study. Schizophr Res 2023; 255:195-202. [PMID: 37004331 DOI: 10.1016/j.schres.2023.03.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 02/10/2023] [Accepted: 03/11/2023] [Indexed: 04/04/2023]
Abstract
OBJECTIVE We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. METHODS DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. RESULTS The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147). CONCLUSIONS In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. TRIAL REGISTRATION clinicaltrials.gov identifier NCT02431702.
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Affiliation(s)
- T A Tishler
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
| | - B M Ellingson
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; UCLA Center for Computer Vision and Imaging Biomarkers, Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
| | - G Salvadore
- Janssen Research and Development, LLC, Titusville, NJ, USA.
| | - P Baker
- Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
| | - I Turkoz
- Janssen Research and Development, LLC, Titusville, NJ, USA.
| | - K L Subotnik
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
| | - C de la Fuente-Sandoval
- Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico.
| | - K H Nuechterlein
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA; Department of Psychology, University of California at Los Angeles, Los Angeles, CA, USA.
| | - L Alphs
- Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
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16
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Witkowski G, Januszko P, Skalski M, Mach A, Wawrzyniak ZM, Poleszak E, Ciszek B, Radziwoń-Zaleska M. Factors Contributing to Risk of Persistence of Positive and Negative Symptoms in Schizophrenia during Hospitalization. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:4592. [PMID: 36901603 PMCID: PMC10001938 DOI: 10.3390/ijerph20054592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 03/01/2023] [Accepted: 03/03/2023] [Indexed: 06/18/2023]
Abstract
The aim of the study was to evaluate factors that may contribute to the persistence of positive, negative and other psychopathological symptoms of schizophrenia. All patients were treated in general psychiatric wards between January 2006 and December 2017. The initial study sample comprised of the medical reports of 600 patients. The main, specified inclusion criterion for the study was schizophrenia as a discharge diagnosis. Medical reports of 262 patients were excluded from the study due to no neuroimaging scans being available. The symptoms were categorised into three groups: positive, negative, and other psychopathological symptoms. The statistical analysis comprised modalities such as demographic data, clinical symptoms, as well as neuroimaging scans linking them to a potential impact of sustaining the mentioned groups of symptoms during the period of hospitalization. The analysis revealed that statistically significant risk factors of persistence of the three groups of symptoms are the elderly age, the increasing toll of hospitalizations, suicidal attempts in medical history, a family history of alcohol abuse, the presence of positive, negative and other psychopathological symptoms on admission to the hospital, as well as the absence of cavum septi pellucidi (CSP). The study showed that addiction to psychotropic drugs and a family history of schizophrenia were more frequent in patients with persistent CSP.
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Affiliation(s)
- Grzegorz Witkowski
- Department of Descriptive and Clinical Anatomy, Medical University of Warsaw, 02-004 Warsaw, Poland
| | - Piotr Januszko
- Department of Psychiatry, Medical University of Warsaw, 00-665 Warsaw, Poland
| | - Michał Skalski
- Department of Psychiatry, Medical University of Warsaw, 00-665 Warsaw, Poland
| | - Anna Mach
- Department of Psychiatry, Medical University of Warsaw, 00-665 Warsaw, Poland
| | - Zbigniew Maciej Wawrzyniak
- Faculty of Electronics and Information Technology, Warsaw University of Technology, 00-665 Warsaw, Poland
| | - Ewa Poleszak
- Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, 20-093 Lublin, Poland
| | - Bogdan Ciszek
- Department of Descriptive and Clinical Anatomy, Medical University of Warsaw, 02-004 Warsaw, Poland
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17
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Vouga Ribeiro N, Tavares V, Bramon E, Toulopoulou T, Valli I, Shergill S, Murray R, Prata D. Effects of psychosis-associated genetic markers on brain volumetry: a systematic review of replicated findings and an independent validation. Psychol Med 2022; 52:1-16. [PMID: 36168994 PMCID: PMC9811278 DOI: 10.1017/s0033291722002896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 08/13/2022] [Accepted: 08/24/2022] [Indexed: 01/12/2023]
Abstract
BACKGROUND Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume. METHODS A systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, 'at risk mental state' or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry. RESULTS We found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance). CONCLUSIONS Most literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.
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Affiliation(s)
- Nuno Vouga Ribeiro
- Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
| | - Vânia Tavares
- Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal
- Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
| | - Elvira Bramon
- Division of Psychiatry, University College London, London, UK
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’ College London, London, UK
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Timothea Toulopoulou
- Department of Psychology & National Magnetic Resonance Research Center (UMRAM), Aysel Sabuncu Brain Research Centre (ASBAM), Bilkent University, Ankara, Turkey
| | - Isabel Valli
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’ College London, London, UK
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Sukhi Shergill
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’ College London, London, UK
| | - Robin Murray
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’ College London, London, UK
| | - Diana Prata
- Instituto de Biofísica e Engenharia Biomédica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal
- Department of Old Age Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
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18
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Avery SN, Huang AS, Sheffield JM, Rogers BP, Vandekar S, Anticevic A, Woodward ND. Development of Thalamocortical Structural Connectivity in Typically Developing and Psychosis Spectrum Youths. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2022; 7:782-792. [PMID: 34655804 PMCID: PMC9008075 DOI: 10.1016/j.bpsc.2021.09.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 09/30/2021] [Accepted: 09/30/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Thalamocortical white matter connectivity is disrupted in psychosis and is hypothesized to play a role in its etiology and associated cognitive impairment. Attenuated cognitive symptoms often begin in adolescence, during a critical phase of white matter and cognitive development. However, little is known about the development of thalamocortical white matter connectivity and its association with cognition. METHODS This study characterized effects of age, sex, psychosis symptomatology, and cognition in thalamocortical networks in a large sample of youths (N = 1144, ages 8-22 years, 46% male) from the Philadelphia Neurodevelopmental Cohort, which included 316 typically developing youths, 330 youths on the psychosis spectrum, and 498 youths with other psychopathology. Probabilistic tractography was used to quantify percent total connectivity between the thalamus and six cortical regions and assess microstructural properties (i.e., fractional anisotropy) of thalamocortical white matter tracts. RESULTS Overall, percent total connectivity of the thalamus was weakly associated with age and was not associated with psychopathology or cognition. In contrast, fractional anisotropy of all thalamocortical tracts increased significantly with age, was generally higher in males than females, and was lowest in youths on the psychosis spectrum. Fractional anisotropy of tracts linking the thalamus to prefrontal and posterior parietal cortices was related to better cognitive function across subjects. CONCLUSIONS By characterizing the pattern of typical development and alterations in those at risk for psychotic disorders, this study provides a foundation for further conceptualization of thalamocortical white matter microstructure as a marker of neurodevelopment supporting cognition and an important risk marker for psychosis.
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Affiliation(s)
- Suzanne N Avery
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Anna S Huang
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Julia M Sheffield
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Baxter P Rogers
- Vanderbilt University Institute of Imaging Sciences, Nashville, Tennessee
| | - Simon Vandekar
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Alan Anticevic
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Neil D Woodward
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee
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19
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DeLisi LE. Commentary on whether progressive brain change underlies the pathology of schizophrenia: Should this even be debated? Schizophr Res 2022; 244:18-20. [PMID: 35567869 DOI: 10.1016/j.schres.2022.05.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Lynn E DeLisi
- Attending Psychiatrist and Director of Faculty Affairs, Department of Psychiatry, Cambridge Health Alliance, Professor of Psychiatry, Harvard Medical School, Cambridge, MA, United States of America.
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20
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Fountoulakis KN, Stahl SM. The effect of first- and second-generation antipsychotics on brain morphology in schizophrenia: A systematic review of longitudinal magnetic resonance studies with a randomized allocation to treatment arms. J Psychopharmacol 2022; 36:428-438. [PMID: 35395911 DOI: 10.1177/02698811221087645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Schizophrenia manifests as loss of brain volume in specific areas in a progressive nature and an important question concerns whether long-term treatment with medications contributes to this. The aim of the current PRISMA systematic review was to search for prospective studies involving randomization to treatment. PROSPERO ID: CRD42020197874. The MEDLINE/PUBMED was searched and it returned 2638 articles; 3 were fulfilling the inclusion criteria. A fourth was published later; they included 359 subjects, of whom 86 were healthy controls, while the rest were first-episode patients, with 91 under olanzapine, 93 under haloperidol, 48 under risperidone, 5 under paliperidone, 6 under ziprasidone, and 30 under placebo. Probably one-third of patients were suffering from a psychotic disorder other than schizophrenia. The consideration of their results suggested that there is no significant difference between these medications concerning their effects on brain structure and also in comparison to healthy subjects. There does not seem to be any strong support to the opinion that medications that treat psychosis cause loss of brain volume in patients with schizophrenia. On the contrary, the data might imply the possible presence of a protective effect for D2, 5-HT2, and NE alpha-2 antagonists (previously called SGAs). However, the literature is limited and focused research in large study samples is essential to clarify the issue, since important numerical differences do exist. The possibility of the results and their heterogeneity to be artifacts secondary to a modification of magnetic resonance imaging (MRI) signal by antipsychotics should not be easily rejected until relevant data are available.
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Affiliation(s)
- Konstantinos N Fountoulakis
- 3rd Department of Psychiatry, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Stephen M Stahl
- Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.,Department of Psychiatry, Cambridge University, Cambridge, UK
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21
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Wang M, Hu K, Fan L, Yan H, Li P, Jiang T, Liu B. Predicting Treatment Response in Schizophrenia With Magnetic Resonance Imaging and Polygenic Risk Score. Front Genet 2022; 13:848205. [PMID: 35186051 PMCID: PMC8847599 DOI: 10.3389/fgene.2022.848205] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 01/12/2022] [Indexed: 11/15/2022] Open
Abstract
Background: Prior studies have separately demonstrated that magnetic resonance imaging (MRI) and schizophrenia polygenic risk score (PRS) are predictive of antipsychotic medication treatment outcomes in schizophrenia. However, it remains unclear whether MRI combined with PRS can provide superior prognostic performance. Besides, the relative importance of these measures in predictions is not investigated. Methods: We collected 57 patients with schizophrenia, all of which had baseline MRI and genotype data. All these patients received approximately 6 weeks of antipsychotic medication treatment. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up. We divided these patients into responders (N = 20) or non-responders (N = 37) based on whether their percentages of PANSS total reduction were above or below 50%. Nine categories of MRI measures and PRSs with 145 different p-value thresholding ranges were calculated. We trained machine learning classifiers with these baseline predictors to identify whether a patient was a responder or non-responder. Results: The extreme gradient boosting (XGBoost) technique was applied to build binary classifiers. Using a leave-one-out cross-validation scheme, we achieved an accuracy of 86% with all MRI and PRS features. Other metrics were also estimated, including sensitivity (85%), specificity (86%), F1-score (81%), and area under the receiver operating characteristic curve (0.86). We found excluding a single feature category of gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), and surface curvature could lead to a maximum accuracy drop of 10.5%. These three categories contributed more than half of the top 10 important features. Besides, removing PRS features caused a modest accuracy drop (8.8%), which was not the least decrease (1.8%) among all feature categories. Conclusions: Our classifier using both MRI and PRS features was stable and not biased to predicting either responder or non-responder. Combining with MRI measures, PRS could provide certain extra predictive power of antipsychotic medication treatment outcomes in schizophrenia. PRS exhibited medium importance in predictions, lower than GMV, ALFF, and surface curvature, but higher than measures of cortical thickness, cortical volume, and surface sulcal depth. Our findings inform the contributions of PRS in predictions of treatment outcomes in schizophrenia.
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Affiliation(s)
- Meng Wang
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.,School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
| | - Ke Hu
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.,School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China
| | - Lingzhong Fan
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.,School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China.,Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
| | - Hao Yan
- Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.,Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China
| | - Peng Li
- Peking University Sixth Hospital/Institute of Mental Health, Beijing, China.,Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China
| | - Tianzi Jiang
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.,School of Artificial Intelligence, University of Chinese Academy of Sciences, Beijing, China.,Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.,Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.,Innovation Academy for Artificial Intelligence, Chinese Academy of Sciences, Beijing, China
| | - Bing Liu
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China.,Chinese Institute for Brain Research, Beijing, China
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22
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Prasad K, Rubin J, Mitra A, Lewis M, Theis N, Muldoon B, Iyengar S, Cape J. Structural covariance networks in schizophrenia: A systematic review Part I. Schizophr Res 2022; 240:1-21. [PMID: 34906884 PMCID: PMC8917984 DOI: 10.1016/j.schres.2021.11.035] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 08/02/2021] [Accepted: 11/23/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Schizophrenia is proposed as a disorder of dysconnectivity. However, examination of complexities of dysconnectivity has been challenging. Structural covariance networks (SCN) provide important insights into the nature of dysconnectivity. This systematic review examines the SCN studies that employed statistical approaches to elucidate covariation of regional morphometric variations. METHODS A systematic search of literature was conducted for peer-reviewed publications using different keywords and keyword combinations for schizophrenia. Fifty-two studies met the criteria. RESULTS Early SCN studies began using correlational structure of selected regions. Over the last 3 decades, methodological approaches have grown increasingly sophisticated from examining selected brain regions using correlation tests on small sample sizes to recent approaches that use advanced statistical methods to examine covariance structure of whole-brain parcellations on larger samples. Although the results are not fully consistent across all studies, a pattern of fronto-temporal, fronto-parietal and fronto-thalamic covariation is reported. Attempts to associate SCN alterations with functional connectivity, to differentiate between disease-related and neurodevelopment-related morphometric changes, and to develop "causality-based" models are being reported. Clinical correlation with outcome, psychotic symptoms, neurocognitive and social cognitive performance are also reported. CONCLUSIONS Application of advanced statistical methods are beginning to provide insights into interesting patterns of regional covariance including correlations with clinical and cognitive data. Although these findings appear similar to morphometric studies, SCNs have the advantage of highlighting topology of these regions and their relationship to the disease and associated variables. Further studies are needed to investigate neurobiological underpinnings of shared covariance, and causal links to clinical domains.
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Affiliation(s)
- Konasale Prasad
- University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213, United States of America; University of Pittsburgh Swanson School of Engineering, 3700 O'Hara St, Pittsburgh, PA 15213, United States of America; VA Pittsburgh Healthcare System, University Dr C, Pittsburgh, PA 15240, United States of America.
| | - Jonathan Rubin
- Department of Mathematics, University of Pittsburgh, 301 Thackeray Hall, Pittsburgh PA 15260
| | - Anirban Mitra
- Department of Statistics, University of Pittsburgh, 1826 Wesley W. Posvar Hall, Pittsburgh PA 15260
| | - Madison Lewis
- University of Pittsburgh Swanson School of Engineering, 3700 O’Hara St, Pittsburgh PA 15213
| | - Nicholas Theis
- University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara St, Pittsburgh PA 15213
| | - Brendan Muldoon
- University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O’Hara St, Pittsburgh PA 15213
| | - Satish Iyengar
- Department of Statistics, University of Pittsburgh, 1826 Wesley W. Posvar Hall, Pittsburgh PA 15260
| | - Joshua Cape
- Department of Statistics, University of Pittsburgh, 1826 Wesley W. Posvar Hall, Pittsburgh PA 15260
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23
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Sun Y, Zhang Z, Kakkos I, Matsopoulos GK, Yuan J, Suckling J, Xu L, Cao S, Chen W, Hu X, Li T, Sim K, Qi P, Sun Y. Inferring the Individual Psychopathologic Deficits with Structural Connectivity in a Longitudinal Cohort of Schizophrenia. IEEE J Biomed Health Inform 2022; 26:2536-2546. [PMID: 34982705 DOI: 10.1109/jbhi.2021.3139701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
The prediction of schizophrenia-related psychopathologic deficits is exceedingly important in the fields of psychiatry and clinical practice. However, objective association of the brain structure alterations to the illness clinical symptoms is challenging. Although, schizophrenia has been characterized as a brain dysconnectivity syndrome, evidence accounting for neuroanatomical network alterations remain scarce. Moreover, the absence of generalized connectome biomarkers for the assessment of illness progression further perplexes the prediction of long-term symptom severity. In this paper, a combination of individualized prediction models with quantitative graph theoretical analysis was adopted, providing a comprehensive appreciation of the extent to which the brain network properties are affected over time in schizophrenia. Specifically, Connectome-based Prediction Models were employed on Structural Connectivity (SC) features, efficiently capturing individual network-related differences, while identifying the anatomical connectivity disturbances contributing to the prediction of psychopathological deficits. Our results demonstrated distinctions among widespread cortical circuits responsible for different domains of symptoms, indicating the complex neural mechanisms underlying schizophrenia. Furthermore, the generated models were able to significantly predict changes of symptoms using SC features at follow-up, while the preserved SC features suggested an association with improved positive and overall symptoms. Moreover, cross-sectional significant deficits were observed in network efficiency and a progressive aberration of global integration in patients compared to healthy controls, representing a group-consensus pathological map, while supporting the dysconnectivity hypothesis.
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24
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Kanahara N, Yamanaka H, Shiko Y, Kawasaki Y, Iyo M. The effects of cumulative antipsychotic dose on brain structures in patients with schizophrenia: Observational study of multiple CT scans over a long-term clinical course. Psychiatry Res Neuroimaging 2022; 319:111422. [PMID: 34856453 DOI: 10.1016/j.pscychresns.2021.111422] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 10/23/2021] [Accepted: 10/28/2021] [Indexed: 10/19/2022]
Abstract
Multiple lines of evidence indicate that antipsychotic agents could affect brain structures of schizophrenia patients. However, the effect of antipsychotic dosage or type on brain structure is uncertain. The present study retrospectively analyzed brain computed tomography (CT) images from a psychiatric hospital to examine the relationship between cumulative dose of antipsychotics and brain volume reduction in schizophrenia patients. A total of 43 patients with repeated relapse episode of psychosis were included and CT scans that were performed an average of 3.2 times per patient during nearly 13 years of follow-up were analyzed. The results revealed significant positive relationships of expansion of cerebrospinal fluid space with cumulative dosage of all antipsychotics and that of typical antipsychotics. Patients treated with antipsychotics including typical antipsychotics exhibited a greater volume reduction compared to patients treated with only atypical antipsychotics. The present study was one of the longest longitudinal studies examining the effects of antipsychotics on brain volume in schizophrenia patients. These results suggest a relation between cumulative lifetime antipsychotic dosage and progressive brain volume reduction in patients with schizophrenia. However, the effects of specific agent on brain structure are still uncertain, and more detailed analysis is needed.
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Affiliation(s)
- Nobuhisa Kanahara
- Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, Chiba, Japan; Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
| | - Hiroshi Yamanaka
- Department of Psychiatry, Chiba Psychiatric Medical Center, Chiba, Japan
| | - Yuki Shiko
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | - Yohei Kawasaki
- Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan
| | - Masaomi Iyo
- Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan
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25
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Yen K, Liu CC, Lin YT, Chien YL, Hsieh MH, Liu CM, Hwang TJ, Liao WH, Hwu HG. Discontinuing Antipsychotic Medication After Remission from First-Episode Psychosis: A Survey of Psychiatrists' Attitudes in Taiwan. Neuropsychiatr Dis Treat 2022; 18:465-475. [PMID: 35261544 PMCID: PMC8898187 DOI: 10.2147/ndt.s339866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/26/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Patients in remission after first-episode psychosis are inclined to discontinue antipsychotic treatment, which may lead to higher risk of relapse and unfavorable outcomes. Paradoxically, also there are evidences suggesting that certain patients may stay well in drug-free condition. Psychiatrists' views towards this dilemma might affect their approaches to these patients, and discrepant attitudes are noted between Western and Asian clinicians. This study aimed to examine psychiatrists' attitudes about discontinuing antipsychotic medications after remission from first-episode psychosis. METHODS Psychiatrists were recruited for this study using convenience sampling. A cross-sectional survey was conducted using a set of questionnaires comprising nine items for attitudes toward medication discontinuation, six vignettes for probing psychiatrists' practice in designated clinical scenarios, and a list of criteria that may affect their responses. RESULTS Responses were provided by 118 psychiatrists, two-thirds men, mean age 39.8 ± 10.1 years and mean experience 12.7 ± 9.7 years. Half of the participants endorsed that fewer than 20% of the remitted patients should stop medication completely; the majority advised that an observation period of 1 year or longer is necessary while discontinuing medication. The majority would not initiate discussion with patients about discontinuing medication. Responding to two case vignettes, those who endorsed that more patients could stop antipsychotics were also more inclined to discuss it with patients, but not consistently in response to the other four case vignettes. Taiwan psychiatrists expressed a wide range of decision-making considerations for discontinuing antipsychotics. CONCLUSION The majority of Taiwan psychiatrists thought it was not feasible to stop medications completely but were willing to consider this option. Once being presented with actual clinical scenarios, many participants hesitated to discontinue antipsychotic medications for various reasons. The proactive attitude of psychiatrists towards conducting clinical trials to test the feasibility of medication discontinuation may help to provide better reference for this clinical dilemma.
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Affiliation(s)
- Ko Yen
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Chung Liu
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Psychiatry, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Yi-Ting Lin
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yi-Ling Chien
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming H Hsieh
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chih-Min Liu
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tzung-Jeng Hwang
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wei-Hsiang Liao
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Hai-Gwo Hwu
- Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.,Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
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26
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Iliuta FP, Manea MC, Budisteanu M, Andrei E, Linca F, Rad F, Cergan R, Ciobanu AM. Magnetic resonance imaging of brain anomalies in adult and pediatric schizophrenia patients: Experience of a Romanian tertiary hospital. Exp Ther Med 2021; 22:1098. [PMID: 34504552 PMCID: PMC8383773 DOI: 10.3892/etm.2021.10532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 06/29/2021] [Indexed: 11/27/2022] Open
Abstract
Schizophrenia is a severe mental illness with a significant impact on the life of both the patient and the patient's family. Magnetic resonance imaging has proven a useful tool for studying structural changes of the brain in schizophrenia. However, interpreting the published literature presents several challenges. Despite thorough research in recent years, which has included anatomopathological, imaging, electrophysiological, and genetic studies, the intimate pathophysiological mechanisms of this disease are not yet fully elucidated. The present study included patients with schizophrenia diagnosed in the psychiatric clinics from the ‘Prof. Dr. Alexandru Obregia’ Clinical Psychiatry Hospital between September 2019 and December 2020. Three Tesla magnetic resonance neuroimaging studies were performed. In a significant number of cases, the neuroimaging studies showed association of cerebral modifications such as enlargement of the Virchow spaces, lesions of the white matter with demyelinating appearance, and inflammatory sinus reactions. Cortical atrophy and hemosiderotic spots were present in a statistically significant proportion in the patient group with an age range of 29-61 years. MRI is indicated as a useful technique in the follow-up process of schizophrenia patients. However, whether the anomalies revealed in this disorder can be utilised as diagnostic biomarkers is still being debated.
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Affiliation(s)
- Floris Petru Iliuta
- Department of Psychiatry, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania.,Department of Psychiatry and Psychology, Faculty of Dental Medicine, 'Carol Davila' University of Medicine and Pharmacy, 010221 Bucharest, Romania
| | - Mihnea Costin Manea
- Department of Psychiatry, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania.,Department of Psychiatry and Psychology, Faculty of Dental Medicine, 'Carol Davila' University of Medicine and Pharmacy, 010221 Bucharest, Romania
| | - Magdalena Budisteanu
- Psychiatry Research Laboratory, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania.,Laboratory of Medical Genetics, 'Victor Babes' National Institute of Pathology, 050096 Bucharest, Romania.,Department of Medical Genetics, Faculty of Medicine, 'Titu Maiorescu' University, 031593 Bucharest, Romania
| | - Emanuela Andrei
- Psychiatry Research Laboratory, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania
| | - Florentina Linca
- Psychiatry Research Laboratory, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania
| | - Florina Rad
- Department of Child and Adolescent Psychiatry, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania.,Discipline of Child and Adolescent Psychiatry, Department of Neurosciences, 050474 Bucharest, Romania
| | - Romica Cergan
- Department of Anatomy, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.,Department of Radiology and Imaging, Clinical Hospital of Orthopedics, Traumatology and Osteoarticular TB, 030167 Bucharest, Romania
| | - Adela Magdalena Ciobanu
- Department of Psychiatry, 'Prof. Dr. Alexandru Obregia' Clinical Hospital of Psychiatry, 041914 Bucharest, Romania.,Discipline of Psychiatry, Department of Neurosciences, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
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27
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Morimoto C, Uematsu A, Nakatani H, Takano Y, Iwashiro N, Abe O, Yamasue H, Kasai K, Koike S. Volumetric differences in gray and white matter of cerebellar Crus I/II across the different clinical stages of schizophrenia. Psychiatry Clin Neurosci 2021; 75:256-264. [PMID: 34081816 DOI: 10.1111/pcn.13277] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 05/20/2021] [Accepted: 05/24/2021] [Indexed: 12/15/2022]
Abstract
AIM Schizophrenia is considered to be a disorder of progressive structural brain abnormalities. Previous studies have indicated that the cerebellar Crus I/II plays a critical role in schizophrenia. We aimed to investigate how specific morphological features in the Crus I/II at different critical stages of the schizophrenia spectrum contribute to the disease. METHODS The study involved 73 participants on the schizophrenia spectrum (28 with ultra-high risk for psychosis [UHR], 17 with first-episode schizophrenia [FES], and 28 with chronic schizophrenia) and 79 healthy controls. We undertook a detailed investigation into differences in Crus I/II volume using a semiautomated segmentation method optimized for the cerebellum. We analyzed the effects of group and sex, as well as their interaction, on Crus I/II volume in gray matter (GM) and white matter (WM). RESULTS Significant group × sex interactions were found in WM volumes of the bilateral Crus I/II; the males with UHR demonstrated significantly larger WM volumes compared with the other male groups, whereas no significant group differences were found in the female groups. Additionally, WM and GM volumes of the Crus I/II had positive associations with symptom severity in the UHR group, whereas, in contrast, GM volumes in the FES group were negatively associated with symptom severity. CONCLUSIONS The present findings provide evidence that the morphology of Crus I/II is involved in schizophrenia in a sex- and disease stage-dependent manner. Additionally, alterations of WM volumes of Crus I/II may have potential as a biological marker of early detection and treatment for individuals with UHR.
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Affiliation(s)
- Chie Morimoto
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Akiko Uematsu
- Center for Evolutionary Cognitive Science, Graduate School of Art and Sciences, The University of Tokyo, Tokyo, Japan
| | - Hironori Nakatani
- Department of Information Media Technology, School of Information and Telecommunication Engineering, Tokai University, Tokyo, Japan
| | - Yosuke Takano
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Norichika Iwashiro
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Osamu Abe
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hidenori Yamasue
- Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan
| | - Kiyoto Kasai
- Department of Neuropsychiatry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Tokyo, Japan.,UTokyo Center for Integrative Science of Human Behaviour (CiSHuB), Tokyo, Japan.,University of Tokyo Institute for Diversity & Adaptation of Human Mind (UTIDAHM), Tokyo, Japan
| | - Shinsuke Koike
- Center for Evolutionary Cognitive Science, Graduate School of Art and Sciences, The University of Tokyo, Tokyo, Japan.,International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Tokyo, Japan.,UTokyo Center for Integrative Science of Human Behaviour (CiSHuB), Tokyo, Japan.,University of Tokyo Institute for Diversity & Adaptation of Human Mind (UTIDAHM), Tokyo, Japan
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28
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Svancer P, Spaniel F. Brain ventricular volume changes in schizophrenia. A narrative review. Neurosci Lett 2021; 759:136065. [PMID: 34146640 DOI: 10.1016/j.neulet.2021.136065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 05/15/2021] [Accepted: 06/14/2021] [Indexed: 11/18/2022]
Abstract
Brain ventricles are among the most studied structures in psychotic illness. In our mini-review we present available evidence on brain ventricle changes during the course of schizophrenia, from high-risk subjects and the first episode of schizophrenia to patients with chronic schizophrenia. We present current findings on the relationship between ventricle changes and level of psychopathology. The potential pathophysiological background of ventricle changes is also discussed. Understanding the dynamics of brain ventricle changes could resolve long-standing questions on the proportion of neurodegenerative and neurodevelopmental processes in the pathophysiology of schizophrenia.
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Affiliation(s)
- Patrik Svancer
- National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - Filip Spaniel
- National Institute of Mental Health, Klecany, Czech Republic; Third Faculty of Medicine, Charles University, Prague, Czech Republic
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29
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Issac AC, Issac TG, Baral R, Bednall TC, Thomas TS. Why you hide what you know: Neuroscience behind knowledge hiding. KNOWLEDGE AND PROCESS MANAGEMENT 2021. [DOI: 10.1002/kpm.1677] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Abraham Cyril Issac
- Department of Management Studies Indian Institute of Technology Madras Chennai India
- Faculty of Business and Law Swinburne University of Technology Melbourne Victoria Australia
| | - Thomas Gregor Issac
- Department of Psychiatry National Institute of Mental Health and Neuroscience (NIMHANS) Bangalore India
| | - Rupashree Baral
- Department of Management Studies Indian Institute of Technology Madras Chennai India
| | - Timothy Colin Bednall
- Faculty of Business and Law Swinburne University of Technology Melbourne Victoria Australia
| | - Tina Susan Thomas
- Department of Information Technology KCG College of Technology Chennai India
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30
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Sasabayashi D, Takahashi T, Takayanagi Y, Suzuki M. Anomalous brain gyrification patterns in major psychiatric disorders: a systematic review and transdiagnostic integration. Transl Psychiatry 2021; 11:176. [PMID: 33731700 PMCID: PMC7969935 DOI: 10.1038/s41398-021-01297-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Revised: 02/14/2021] [Accepted: 02/24/2021] [Indexed: 01/31/2023] Open
Abstract
Anomalous patterns of brain gyrification have been reported in major psychiatric disorders, presumably reflecting their neurodevelopmental pathology. However, previous reports presented conflicting results of patients having hyper-, hypo-, or normal gyrification patterns and lacking in transdiagnostic consideration. In this article, we systematically review previous magnetic resonance imaging studies of brain gyrification in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder at varying illness stages, highlighting the gyral pattern trajectory for each disorder. Patients with each psychiatric disorder may exhibit deviated primary gyri formation under neurodevelopmental genetic control in their fetal life and infancy, and then exhibit higher-order gyral changes due to mechanical stress from active brain changes (e.g., progressive reduction of gray matter volume and white matter integrity) thereafter, representing diversely altered pattern trajectories from those of healthy controls. Based on the patterns of local connectivity and changes in neurodevelopmental gene expression in major psychiatric disorders, we propose an overarching model that spans the diagnoses to explain how deviated gyral pattern trajectories map onto clinical manifestations (e.g., psychosis, mood dysregulation, and cognitive impairments), focusing on the common and distinct gyral pattern changes across the disorders in addition to their correlations with specific clinical features. This comprehensive understanding of the role of brain gyrification pattern on the pathophysiology may help to optimize the prediction and diagnosis of psychiatric disorders using objective biomarkers, as well as provide a novel nosology informed by neural circuits beyond the current descriptive diagnostics.
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Affiliation(s)
- Daiki Sasabayashi
- Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan. .,Research Center for Idling Brain Science, University of Toyama, Toyama, Japan.
| | - Tsutomu Takahashi
- grid.267346.20000 0001 2171 836XDepartment of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan ,grid.267346.20000 0001 2171 836XResearch Center for Idling Brain Science, University of Toyama, Toyama, Japan
| | - Yoichiro Takayanagi
- grid.267346.20000 0001 2171 836XDepartment of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan ,Arisawabashi Hospital, Toyama, Japan
| | - Michio Suzuki
- grid.267346.20000 0001 2171 836XDepartment of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan ,grid.267346.20000 0001 2171 836XResearch Center for Idling Brain Science, University of Toyama, Toyama, Japan
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31
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Nath M, Wong TP, Srivastava LK. Neurodevelopmental insights into circuit dysconnectivity in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2021; 104:110047. [PMID: 32721441 DOI: 10.1016/j.pnpbp.2020.110047] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 07/01/2020] [Accepted: 07/21/2020] [Indexed: 11/30/2022]
Abstract
Schizophrenia is increasingly being recognized as a disorder of brain circuits of developmental origin. Animal models, however, have been technically limited in exploring the effects of early developmental circuit abnormalities on the maturation of the brain and associated behavioural outputs. This review discusses evidence of the developmental emergence of circuit abnormalities in schizophrenia, followed by a critical assessment on how animal models need to be adapted through optimized tools in order to spatially and temporally manipulate early developmental events, thereby providing insight into the causal contribution of developmental perturbations to schizophrenia.
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Affiliation(s)
- Moushumi Nath
- Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Canada.
| | - Tak Pan Wong
- Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Canada
| | - Lalit K Srivastava
- Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Canada
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32
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Palaniyappan L, Sukumar N. Reconsidering brain tissue changes as a mechanistic focus for early intervention in psychiatry. J Psychiatry Neurosci 2020; 45. [PMID: 33119489 PMCID: PMC7595740 DOI: 10.1503/jpn.200172] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Affiliation(s)
- Lena Palaniyappan
- From the Robarts Research Institute, Western University (Palaniyappan); the Department of Psychiatry, Western University (Palaniyappan, Sukumar); the Lawson Health Research Institute, Imaging Division (Palaniyappan); and the Department of Medical Biophysics, Western University (Palaniyappan), London, Ont., Canada
| | - Niron Sukumar
- From the Robarts Research Institute, Western University (Palaniyappan); the Department of Psychiatry, Western University (Palaniyappan, Sukumar); the Lawson Health Research Institute, Imaging Division (Palaniyappan); and the Department of Medical Biophysics, Western University (Palaniyappan), London, Ont., Canada
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33
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Luo C, Lencer R, Hu N, Xiao Y, Zhang W, Li S, Lui S, Gong Q. Characteristics of White Matter Structural Networks in Chronic Schizophrenia Treated With Clozapine or Risperidone and Those Never Treated. Int J Neuropsychopharmacol 2020; 23:799-810. [PMID: 32808036 PMCID: PMC7770521 DOI: 10.1093/ijnp/pyaa061] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 07/24/2020] [Accepted: 08/12/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Despite its benefits, a major concern regarding antipsychotic treatment is its possible impact on the brain's structure and function. This study sought to explore the characteristics of white matter structural networks in chronic never-treated schizophrenia and those treated with clozapine or risperidone, and its potential association with cognitive function. METHODS Diffusion tensor imaging was performed on a unique sample of 34 schizophrenia patients treated with antipsychotic monotherapy for over 5 years (17 treated with clozapine and 17 treated with risperidone), 17 never-treated schizophrenia patients with illness duration over 5 years, and 27 healthy control participants. Graph theory and network-based statistic approaches were employed. RESULTS We observed a disrupted organization of white matter structural networks as well as decreased nodal and connectivity characteristics across the schizophrenia groups, mainly involving thalamus, prefrontal, and occipital regions. Alterations in nodal and connectivity characteristics were relatively milder in risperidone-treated patients than clozapine-treated patients and never-treated patients. Altered global network measures were significantly associated with cognitive performance levels. Structural connectivity as reflected by network-based statistic mediated the difference in cognitive performance levels between clozapine-treated and risperidone-treated patients. LIMITATIONS These results are constrained by the lack of random assignment to different types of antipsychotic treatment. CONCLUSION These findings provide insight into the white matter structural network deficits in patients with chronic schizophrenia, either being treated or untreated, and suggest white matter structural networks supporting cognitive function may benefit from antipsychotic treatment, especially in those treated with risperidone.
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Affiliation(s)
- Chunyan Luo
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China
| | - Rebekka Lencer
- Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany
| | - Na Hu
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China
| | - Yuan Xiao
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China
| | - Wenjing Zhang
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China
| | - Siyi Li
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China
| | - Su Lui
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China,Correspondence: Dr Su Lui, MD, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, No. 37 Guoxue Xiang, Chengdu 610041, China ()
| | - Qiyong Gong
- Huaxi MR Research Center (HMRRC), Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China,Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, China
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34
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Chwa WJ, Tishler TA, Raymond C, Tran C, Anwar F, Villablanca JP, Ventura J, Subotnik KL, Nuechterlein KH, Ellingson BM. Association between cortical volume and gray-white matter contrast with second generation antipsychotic medication exposure in first episode male schizophrenia patients. Schizophr Res 2020; 222:397-410. [PMID: 32487466 PMCID: PMC7572538 DOI: 10.1016/j.schres.2020.03.073] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 01/06/2020] [Accepted: 03/31/2020] [Indexed: 01/19/2023]
Abstract
This cross-sectional study examines the differences in cortical volume and gray-to-white matter contrast (GWC) in first episode schizophrenia patients (SCZ) compared to healthy control participants (HC) and in SCZ patients as a function of exposure to second generation antipsychotic medication. We hypothesize 1) SCZ exhibit regionally lower cortical volumes relative to HCs, 2) cortical volume will be greater with longer exposure to second generation antipsychotics prior to the MRI scan, and 3) lower GWC with longer exposure to second generation antipsychotics prior to the MRI scan, suggesting more blurring from greater intracortical myelin. To accomplish this, MRI scans from 71 male SCZ patients treated with second generation oral risperidone and 42 male HCs were examined. 3D T1-weighted MPRAGE images collected at 1.5T were used to estimate cortical volume and GWC by sampling signal intensity at 30% within the cortical ribbon. Average cortical volume and GWC were calculated and compared between SCZ and HC. Cortical volume and GWC in SCZ patients were correlated with duration of medication exposure for the time period prior to the scan. First-episode SCZ patients had significantly lower cortical volume compared to HCs in bilateral temporal, superior and rostral frontal, postcentral gyral, and parahippocampal regions. In SCZ patients, greater cortical volume was associated with (log-transformed) duration of second-generation antipsychotic medication exposure in bilateral precuneus, right lingual, and right superior parietal regions. Lower GWC was correlated with longer duration of medication exposure bilaterally in the superior frontal lobes. In summary, second generation antipsychotics may increase cortical volume and decrease GWC in first episode SCZ patients.
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Affiliation(s)
- Won Jong Chwa
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA,Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Todd A. Tishler
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Catalina Raymond
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Cathy Tran
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Faizan Anwar
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - J. Pablo Villablanca
- Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Joseph Ventura
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Kenneth L. Subotnik
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
| | - Keith H. Nuechterlein
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA,Department of Psychology, University of California Los Angeles, Los Angeles, CA
| | - Benjamin M. Ellingson
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA,Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA
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35
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Tronchin G, Akudjedu TN, Ahmed M, Holleran L, Hallahan B, Cannon DM, McDonald C. Progressive subcortical volume loss in treatment-resistant schizophrenia patients after commencing clozapine treatment. Neuropsychopharmacology 2020; 45:1353-1361. [PMID: 32268345 PMCID: PMC7298040 DOI: 10.1038/s41386-020-0665-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 03/20/2020] [Accepted: 03/24/2020] [Indexed: 02/07/2023]
Abstract
The association of antipsychotic medication with abnormal brain morphometry in schizophrenia remains uncertain. This study investigated subcortical morphometric changes 6 months after switching treatment to clozapine in patients with treatment-resistant schizophrenia compared with healthy volunteers, and the relationships between longitudinal volume changes and clinical variables. In total, 1.5T MRI images were acquired at baseline before commencing clozapine and again after 6 months of treatment for 33 patients with treatment-resistant schizophrenia and 31 controls, and processed using the longitudinal pipeline of Freesurfer v.5.3.0. Two-way repeated MANCOVA was used to assess group differences in subcortical volumes over time and partial correlations to determine association with clinical variables. Whereas no significant subcortical volume differences were found between patients and controls at baseline (F(8,52) = 1.79; p = 0.101), there was a significant interaction between time, group and structure (F(7,143) = 52.54; p < 0.001). Corrected post-hoc analyses demonstrated that patients had significant enlargement of lateral ventricles (F(1,59) = 48.89; p < 0.001) and reduction of thalamus (F(1,59) = 34.85; p < 0.001), caudate (F(1,59) = 59.35; p < 0.001), putamen (F(1,59) = 87.20; p < 0.001) and hippocampus (F(1,59) = 14.49; p < 0.001) volumes. Thalamus and putamen volume reduction was associated with improvement in PANSS (r = 0.42; p = 0.021, r = 0.39; p = 0.033), SANS (r = 0.36; p = 0.049, r = 0.40; p = 0.027) and GAF (r = -0.39; p = 0.038, r = -0.42; p = 0.024) scores. Reduced thalamic volume over time was associated with increased serum clozapine level at follow-up (r = -0.44; p = 0.010). Patients with treatment-resistant schizophrenia display progressive subcortical volume deficits after switching to clozapine despite experiencing symptomatic improvement. Thalamo-striatal progressive volumetric deficit associated with symptomatic improvement after clozapine exposure may reflect an adaptive response related to improved outcome rather than a harmful process.
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Affiliation(s)
- Giulia Tronchin
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland.
| | - Theophilus N Akudjedu
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland
- Institute of Medical Imaging & Visualisation, Faculty of Health & Social Science, Department of Medical Science & Public Science, Bournemouth University, Bournemouth, UK
| | - Mohamed Ahmed
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland
| | - Laurena Holleran
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland
| | - Brian Hallahan
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland
| | - Dara M Cannon
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland
| | - Colm McDonald
- Centre for Neuroimaging & Cognitive Genomics (NICOG), Clinical Neuroimaging Laboratory, NCBES Galway Neuroscience Centre, College of Medicine Nursing and Health Sciences, National University of Ireland Galway, Galway, H91TK33, Ireland
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Fountoulakis KN, Moeller HJ, Kasper S, Tamminga C, Yamawaki S, Kahn R, Tandon R, Correll CU, Javed A. The report of the joint WPA/CINP workgroup on the use and usefulness of antipsychotic medication in the treatment of schizophrenia. CNS Spectr 2020; 26:1-25. [PMID: 32594935 DOI: 10.1017/s1092852920001546] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
This is a report of a joint World Psychiatric Association/International College of Neuropsychopharmacology (WPA/CINP) workgroup concerning the risk/benefit ratio of antipsychotics in the treatment of schizophrenia. It utilized a selective but, within topic, comprehensive review of the literature, taking into consideration all the recently discussed arguments on the matter and avoiding taking sides when the results in the literature were equivocal. The workgroup's conclusions suggested that antipsychotics are efficacious both during the acute and the maintenance phase, and that the current data do not support the existence of a supersensitivity rebound psychosis. Long-term treated patients have better overall outcome and lower mortality than those not taking antipsychotics. Longer duration of untreated psychosis and relapses are modestly related to worse outcome. Loss of brain volume is evident already at first episode and concerns loss of neuropil volume rather than cell loss. Progression of volume loss probably happens in a subgroup of patients with worse prognosis. In humans, antipsychotic treatment neither causes nor worsens volume loss, while there are some data in favor for a protective effect. Schizophrenia manifests 2 to 3 times higher mortality vs the general population, and treatment with antipsychotics includes a number of dangers, including tardive dyskinesia and metabolic syndrome; however, antipsychotic treatment is related to lower mortality, including cardiovascular mortality. In conclusion, the literature strongly supports the use of antipsychotics both during the acute and the maintenance phase without suggesting that it is wise to discontinue antipsychotics after a certain period of time. Antipsychotic treatment improves long-term outcomes and lowers overall and specific-cause mortality.
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Affiliation(s)
- Konstantinos N Fountoulakis
- 3rd Department of Psychiatry, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Hans-Jurgen Moeller
- Department of Psychiatry, Ludwig Maximilian University of Munich, Munich, Germany
| | - Siegfried Kasper
- Universitätsklinik für Psychiatrie und Psychotherapie, Medizinische Universität Wien, Vienna, Austria
| | - Carol Tamminga
- Department of Psychiatry, UT Southwestern Medical Center, Dallas, Texas, USA
| | - Shigeto Yamawaki
- Center for Brain, Mind and KANSEI Sciences Research, Hiroshima University, Hiroshima, Japan
| | - Rene Kahn
- Department of Psychiatry and Behavioral Health System, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Rajiv Tandon
- Department of Psychiatry, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo, Michigan, USA
| | - Christoph U Correll
- Department of Psychiatry, Northwell Health, The Zucker Hillside Hospital, Glen Oaks, New York, USA
- Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Afzal Javed
- Warwick Medical School, University of Warwick, Coventry, United Kingdom
- Pakistan Psychiatric Research Centre, Fountain House, Lahore, Pakistan
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Gouvêa-Junqueira D, Falvella ACB, Antunes ASLM, Seabra G, Brandão-Teles C, Martins-de-Souza D, Crunfli F. Novel Treatment Strategies Targeting Myelin and Oligodendrocyte Dysfunction in Schizophrenia. Front Psychiatry 2020; 11:379. [PMID: 32425837 PMCID: PMC7203658 DOI: 10.3389/fpsyt.2020.00379] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 04/15/2020] [Indexed: 12/12/2022] Open
Abstract
Oligodendrocytes are the glial cells responsible for the formation of the myelin sheath around axons. During neurodevelopment, oligodendrocytes undergo maturation and differentiation, and later remyelination in adulthood. Abnormalities in these processes have been associated with behavioral and cognitive dysfunctions and the development of various mental illnesses like schizophrenia. Several studies have implicated oligodendrocyte dysfunction and myelin abnormalities in the disorder, together with altered expression of myelin-related genes such as Olig2, CNP, and NRG1. However, the molecular mechanisms subjacent of these alterations remain elusive. Schizophrenia is a severe, chronic psychiatric disorder affecting more than 23 million individuals worldwide and its symptoms usually appear at the beginning of adulthood. Currently, the major therapeutic strategy for schizophrenia relies on the use of antipsychotics. Despite their widespread use, the effects of antipsychotics on glial cells, especially oligodendrocytes, remain unclear. Thus, in this review we highlight the current knowledge regarding oligodendrocyte dysfunction in schizophrenia, compiling data from (epi)genetic studies and up-to-date models to investigate the role of oligodendrocytes in the disorder. In addition, we examined potential targets currently investigated for the improvement of schizophrenia symptoms. Research in this area has been investigating potential beneficial compounds, including the D-amino acids D-aspartate and D-serine, that act as NMDA receptor agonists, modulating the glutamatergic signaling; the antioxidant N-acetylcysteine, a precursor in the synthesis of glutathione, protecting against the redox imbalance; as well as lithium, an inhibitor of glycogen synthase kinase 3β (GSK3β) signaling, contributing to oligodendrocyte survival and functioning. In conclusion, there is strong evidence linking oligodendrocyte dysfunction to the development of schizophrenia. Hence, a better understanding of oligodendrocyte differentiation, as well as the effects of antipsychotic medication in these cells, could have potential implications for understanding the development of schizophrenia and finding new targets for drug development.
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Affiliation(s)
- Danielle Gouvêa-Junqueira
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Ana Caroline Brambilla Falvella
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - André Saraiva Leão Marcelo Antunes
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Gabriela Seabra
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Caroline Brandão-Teles
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
| | - Daniel Martins-de-Souza
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, Brazil
- Instituto Nacional de Biomarcadores em Neuropsiquiatria, Conselho Nacional de Desenvolvimento Científico e Tecnológico, São Paulo, Brazil
- D′Or Institute for Research and Education (IDOR), São Paulo, Brazil
| | - Fernanda Crunfli
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas, Campinas, Brazil
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van Haren N, Cahn W, Hulshoff Pol H, Kahn R. Schizophrenia as a progressive brain disease. Eur Psychiatry 2020; 23:245-54. [DOI: 10.1016/j.eurpsy.2007.10.013] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2007] [Revised: 10/11/2007] [Accepted: 10/18/2007] [Indexed: 01/06/2023] Open
Abstract
AbstractThere is convincing evidence that schizophrenia is characterized by abnormalities in brain volume. At the Department of Psychiatry of the University Medical Centre Utrecht, Netherlands, we have been carrying out neuroimaging studies in schizophrenia since 1995. We focused our research on three main questions. First, are brain volume abnormalities static or progressive in nature? Secondly, can brain volume abnormalities in schizophrenia be explained (in part) by genetic influences? Finally, what environmental factors are associated with the brain volume abnormalities in schizophrenia?Based on our findings we suggest that schizophrenia is a progressive brain disease. We showed different age-related trajectories of brain tissue loss suggesting that brain maturation that occurs in the third and fourth decade of life is abnormal in schizophrenia. Moreover, brain volume has been shown to be a useful phenotype for studying schizophrenia. Brain volume is highly heritable and twin and family studies show that unaffected relatives show abnormalities that are similar, but usually present to a lesser extent, to those found in the patients. However, also environmental factors play a role. Medication intake is indeed a confounding factor when interpreting brain volume (change) abnormalities, while independent of antipsychotic medication intake brain volume abnormalities appear influenced by the outcome of the illness.In conclusion, schizophrenia can be considered as a progressive brain disease with brain volume abnormalities that are for a large part influenced by genetic factors. Whether the progressive volume change is also mediated by genes awaits the results of longitudinal twin analyses. One of the main challenges for the coming years, however, will be the search for gene-by-environment interactions on the progressive brain changes in schizophrenia.
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Achieving the Lowest Effective Antipsychotic Dose for Patients with Remitted Psychosis: A Proposed Guided Dose-Reduction Algorithm. CNS Drugs 2020; 34:117-126. [PMID: 31741178 DOI: 10.1007/s40263-019-00682-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Continuing antipsychotic treatment in patients with schizophrenia under clinical remission remains controversial. Even though the mainstream opinion declares an outweighed balance against medication discontinuation, recent reviews and critiques suggest that some patients may remain symptom free and well functioning after stopping antipsychotics, but few predictors can identify who can try medication discontinuation, whilst no guidelines exist for reducing medication to reach the lowest effective dose safely. Analyzing the findings from studies employing different methodologies, adopting evidence from pharmacodynamic research, and observing dose reduction in stable patients, as well as taking inspiration from the metaphor of the Cantor set in natural philosophy, we introduce an alternative solution and propose a guided dose-reduction algorithm that follows a set of clear precautions and instructions. The algorithm recommends only a fraction (no more than 25%) of the dosage to be reduced at a time, with at least a 6-month stabilization period required before reducing another 25% of the dose. Patients are empowered to actively participate in decision making when they are ready for further dose tapering, or should they retreat to a previous dosage if warning signs of a relapse re-emerge. An intermittent or irregular dosing schedule can be used to adapt this algorithm to real-world practice. Our preliminary findings suggest that patients with remitted psychosis can do well along this path. We anticipate that this approach can help optimize the risk-benefit ratio and instill a hope in patients with schizophrenia that they can maintain in stable remission under a lower antipsychotic dose without an increased risk of relapse.
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Fitzsimmons J, Rosa P, Sydnor VJ, Reid BE, Makris N, Goldstein JM, Mesholam-Gately RI, Woodberry K, Wojcik J, McCarley RW, Seidman LJ, Shenton ME, Kubicki M. Cingulum bundle abnormalities and risk for schizophrenia. Schizophr Res 2020; 215:385-391. [PMID: 31477373 DOI: 10.1016/j.schres.2019.08.017] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 07/22/2019] [Accepted: 08/15/2019] [Indexed: 01/13/2023]
Abstract
BACKGROUND The cingulum bundle (CB) is a major white matter fiber tract of the limbic system that underlies cingulate cortex, passing longitudinally over the corpus callosum. The connectivity of this white matter fiber tract plays a major role in emotional expression, attention, motivation, and working memory, all of which are affected in schizophrenia. Myelin related CB abnormalities have also been implicated in schizophrenia. The purpose of this study is to determine whether or not CB abnormalities are evident in individuals at clinical high risk (CHR) for psychosis, and whether or not cognitive deficits in the domains subserved by CB are related to its structural abnormalities. METHODS Diffusion Tensor Imaging (DTI) was performed on a 3 T magnet. DT tractography was used to evaluate CB in 20 individuals meeting CHR criteria (13 males/7 females) and 23 healthy controls (12 males/11 females) group matched on age, gender, parental socioeconomic status, education, and handedness. Fractional anisotropy (FA), a measure of white matter coherence and integrity, radial diffusivity (RD), thought to reflect myelin integrity, trace, a possible marker of atrophy, and axial diffusivity (AD), thought to reflect axonal integrity, were averaged over the entire tract and used to investigate CB abnormalities in individuals at CHR for psychosis compared with healthy controls. RESULTS Significant group differences were found between individuals at CHR for psychosis and controls for FA (p = 0.028), RD (p = 0.03) and trace (p = 0.031), but not for AD (p = 0.09). We did not find any significant correlations between DTI measures and clinical symptoms. CONCLUSION These findings suggest abnormalities (possibly myelin related) in the CB in individuals at CHR for psychosis.
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Affiliation(s)
- Jennifer Fitzsimmons
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America.
| | - Pedro Rosa
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Laboratory of Psychiatric Neuroimaging (LIM-21), Department & Institute of Psychiatry, Faculty of Medicine, Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, São Paulo, Brazil; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Valerie J Sydnor
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Benjamin E Reid
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Nikos Makris
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Jill M Goldstein
- Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States of America
| | - Raquelle I Mesholam-Gately
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America
| | - Kristen Woodberry
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America
| | - Joanne Wojcik
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America
| | - Robert W McCarley
- Department of Psychiatry, VA Boston Healthcare System, Harvard Medical School, Boston, MA, United States of America
| | - Larry J Seidman
- Beth Israel Deaconess Medical Center-Massachusetts Mental Health Center, Public Psychiatry Division, Harvard Medical School, Boston, MA, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Martha E Shenton
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Research and Development, VA Boston Healthcare System, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
| | - Marek Kubicki
- Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States of America; Psychiatry Neuroimaging Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States of America
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Influence of cognitive reserve in schizophrenia: A systematic review. Neurosci Biobehav Rev 2020; 108:149-159. [DOI: 10.1016/j.neubiorev.2019.10.019] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 10/10/2019] [Accepted: 10/26/2019] [Indexed: 01/08/2023]
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Koelkebeck K, Dannlowski U, Ohrmann P, Suslow T, Murai T, Bauer J, Pedersen A, Matsukawa N, Son S, Haidl T, Miyata J. Gray matter volume reductions in patients with schizophrenia: A replication study across two cultural backgrounds. Psychiatry Res Neuroimaging 2019; 292:32-40. [PMID: 31499256 DOI: 10.1016/j.pscychresns.2019.08.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/21/2019] [Accepted: 08/30/2019] [Indexed: 01/14/2023]
Abstract
Structural gray matter (GM) volume reductions in patients with schizophrenia have rarely been replicated across two different sites, the impact of culture and clinical characteristics remains unresolved. Hence, we assessed GM volume reductions in patients with schizophrenia using 3 T magnetic resonace imaging to replicate results across two independent and culturally different backgrounds (Germany, Japan), and to investigate the impact of brain volume reductions on clinical characteristics. In total, 163 German (80 patients) and 203 Japanese (83 patients) participants were included in the analysis. Voxel-based morphometry (VBM) was used to investigate structural differences between the groups and across the two sites, comparing local GM volumes. Clinical variables were used to analyze effects unrelated to the socio-cultural background. Across both data sets, widespread GM reductions in frontal and temporal cortical parts were found between patients and controls, indicating strong effects of diagnosis and only small effects of site. The investigation of clinical characteristics revealed the strongest effects for chlorpromazine equivalents on GM volume reductions primarily in the Japanese sample. Although the effects of site are small, several brain regions do not overlap between the two groups. Thus, GM may be affected differently at the two sites in patients with schizophrenia.
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Affiliation(s)
- Katja Koelkebeck
- Department of Psychiatry and Psychotherapy, University of Muenster, School of Medicine, Albert-Schweitzer-Campus 1, Building A9, 48149 Muenster, Germany.
| | - Udo Dannlowski
- Department of Psychiatry and Psychotherapy, University of Muenster, School of Medicine, Albert-Schweitzer-Campus 1, Building A9, 48149 Muenster, Germany
| | - Patricia Ohrmann
- Department of Psychiatry and Psychotherapy, University of Muenster, School of Medicine, Albert-Schweitzer-Campus 1, Building A9, 48149 Muenster, Germany
| | - Thomas Suslow
- University of Leipzig, Department of Psychosomatic Medicine and Psychotherapy, Semmelweisstrasse 10, 04103 Leipzig, Germany
| | - Toshiya Murai
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Jochen Bauer
- Institute of Clinical Radiology, Medical Faculty - University of Muenster - and University Hospital Muenster, Albert-Schweitzer-Campus 1, Building A1, 48149 Muenster, Germany
| | - Anya Pedersen
- Clinical Psychology and Psychotherapy, University of Kiel, Olshausenstrasse 62, 24118 Kiel, Germany
| | - Noriko Matsukawa
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Shuraku Son
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| | - Theresa Haidl
- Department of Psychiatry and Psychotherapy, University of Cologne, Kerpener Strasse 62, 50934 Cologne, Germany
| | - Jun Miyata
- Department of Psychiatry, University of Kyoto, School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
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Saghazadeh A, Mahmoudi M, Shahrokhi S, Mojarrad M, Dastmardi M, Mirbeyk M, Rezaei N. Trace elements in schizophrenia: a systematic review and meta-analysis of 39 studies (N = 5151 participants). Nutr Rev 2019; 78:278-303. [DOI: 10.1093/nutrit/nuz059] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 02/14/2019] [Accepted: 06/15/2019] [Indexed: 01/11/2023] Open
Abstract
Abstract
Context
The pathogenesis of schizophrenia appears to be multifaceted.
Objective
The aim of this meta-analysis of studies that investigated blood and hair concentrations of trace elements in people diagnosed with schizophrenia was to determine whether levels of trace elements in patients with schizophrenia differ from those in healthy individuals.
Data Sources
The PubMed, Scopus, and Web of Science databases were searched to January 2018.
Study Selection
Studies that compared concentrations of trace elements in patients with schizophrenia with those in healthy controls, in patients with schizophrenia under different treatment regimens, or in patients with schizophrenia at different stages of disease were included.
Data Extraction
Data on study and sample characteristics and measures of trace elements were extracted.
Results
Thirty-nine studies with a total of 5151 participants were included. Meta-analysis of combined plasma and serum data showed higher levels of copper, lower levels of iron, and lower levels of zinc among patients with schizophrenia vs controls without schizophrenia. Subgroup analyses confirmed the following: higher levels of copper in plasma, in users of typical antipsychotic drugs, and in males; lower levels of zinc in serum, in patients in Asia, in drug-naive/drug-free patients, and in inpatients; lower levels of iron in serum, in patients in Asia, in drug-naive/drug-free patients, in patients on antipsychotic drugs, in inpatients, in patients with acute or newly diagnosed schizophrenia, in patients with chronic or previously diagnosed schizophrenia, and in males; and lower levels of manganese in plasma and in patients with chronic or previously diagnosed schizophrenia.
Conclusions
This meta-analysis provides evidence of an excess of copper, along with deficiencies of zinc, iron, and manganese, in patients with schizophrenia.
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Affiliation(s)
- Amene Saghazadeh
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- MetaCognition Interest Group, Universal Scientific Education and Research Network, Tehran, Iran
| | - Maryam Mahmoudi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Dietitians and Nutrition Experts Team, Universal Scientific Education and Research Network, Tehran, Iran
| | - Shayan Shahrokhi
- NeuroImmunology Research Association, Universal Scientific Education and Research Network, Tehran, Iran
| | - Maryam Mojarrad
- NeuroImmunology Research Association, Universal Scientific Education and Research Network, Tehran, Iran
| | - Maedeh Dastmardi
- NeuroImmunology Research Association, Universal Scientific Education and Research Network, Tehran, Iran
| | - Mona Mirbeyk
- NeuroImmunology Research Association, Universal Scientific Education and Research Network, Tehran, Iran
| | - Nima Rezaei
- Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Molecular Immunology Research Center, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Systematic Review and Meta-analysis Expert Group, Universal Scientific Education and Research Network, Boston, Massachusetts, USA
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Duchatel RJ, Shannon Weickert C, Tooney PA. White matter neuron biology and neuropathology in schizophrenia. NPJ SCHIZOPHRENIA 2019; 5:10. [PMID: 31285426 PMCID: PMC6614474 DOI: 10.1038/s41537-019-0078-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Accepted: 06/06/2019] [Indexed: 12/17/2022]
Abstract
Schizophrenia is considered a neurodevelopmental disorder as it often manifests before full brain maturation and is also a cerebral cortical disorder where deficits in GABAergic interneurons are prominent. Whilst most neurons are located in cortical and subcortical grey matter regions, a smaller population of neurons reside in white matter tracts of the primate and to a lesser extent, the rodent brain, subjacent to the cortex. These interstitial white matter neurons (IWMNs) have been identified with general markers for neurons [e.g., neuronal nuclear antigen (NeuN)] and with specific markers for neuronal subtypes such as GABAergic neurons. Studies of IWMNs in schizophrenia have primarily focused on their density underneath cortical areas known to be affected in schizophrenia such as the dorsolateral prefrontal cortex. Most of these studies of postmortem brains have identified increased NeuN+ and GABAergic IWMN density in people with schizophrenia compared to healthy controls. Whether IWMNs are involved in the pathogenesis of schizophrenia or if they are increased because of the cortical pathology in schizophrenia is unknown. We also do not understand how increased IWMN might contribute to brain dysfunction in the disorder. Here we review the literature on IWMN pathology in schizophrenia. We provide insight into the postulated functional significance of these neurons including how they may contribute to the pathophysiology of schizophrenia.
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Affiliation(s)
- Ryan J Duchatel
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia
- Priority Centre for Brain and Mental Health Research and Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, 2308, Australia
| | - Cynthia Shannon Weickert
- Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW, 2031, Australia
- School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia
- Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, New York, 13210, USA
| | - Paul A Tooney
- School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia.
- Priority Centre for Brain and Mental Health Research and Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW, 2308, Australia.
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45
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Reduced frontal slow wave density during sleep in first-episode psychosis. Schizophr Res 2019; 206:318-324. [PMID: 30377012 DOI: 10.1016/j.schres.2018.10.024] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 10/21/2018] [Accepted: 10/23/2018] [Indexed: 01/29/2023]
Abstract
BACKGROUND Sleep disturbances are commonly reported in psychotic patients and often contribute to the manifestation and severity of their symptoms. Slow waves characterize the deepest stage of NREM sleep, and their occurrence is critical for restorative sleep. Slow wave abnormalities have been reported in patient with schizophrenia, especially when experiencing an exacerbation of psychosis. However, their presence and delineation, with an emphasis on topography, in first-episode psychosis patients (FEP) have not yet been characterized. METHODS We performed sleep high density (hd)-EEG recordings in twenty FEP patients and twenty healthy control subjects (HC). Slow wave activity (SWA) and several other slow wave parameters, e.g. density, amplitude, up- and down-slopes, were calculated at each electrode location and compared across groups. Additionally, the association between slow wave characteristics and clinical symptoms was assessed. RESULTS FEP patients showed a reduction selectively in slow-wave density relative to HC, and this reduction was significant in a large frontal area, including channels overlying the prefrontal cortex. Furthermore, slow wave density was inversely correlated with the severity of FEP positive symptoms. CONCLUSIONS Abnormalities in slow waves are present at the beginning of psychosis, occur in frontal-prefrontal regions that are highly dysfunctional in psychotic patients, and are associated with their positive symptom severity. Building on these findings, future work will help establish the direction of these associations (i.e., if clinical symptoms precede, coincide, or follow SW deficits), which will determine whether ameliorating slow wave sleep deficits is a viable treatment target in early psychosis.
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46
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Lin Y, Li M, Zhou Y, Deng W, Ma X, Wang Q, Guo W, Li Y, Jiang L, Hu X, Zhang N, Li T. Age-Related Reduction in Cortical Thickness in First-Episode Treatment-Naïve Patients with Schizophrenia. Neurosci Bull 2019; 35:688-696. [PMID: 30790217 DOI: 10.1007/s12264-019-00348-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Accepted: 10/25/2018] [Indexed: 02/05/2023] Open
Abstract
Substantial evidence supports the neurodevelopmental hypothesis of schizophrenia. Meanwhile, progressive neurodegenerative processes have also been reported, leading to the hypothesis that neurodegeneration is a characteristic component in the neuropathology of schizophrenia. However, a major challenge for the neurodegenerative hypothesis is that antipsychotic drugs used by patients have profound impact on brain structures. To clarify this potential confounding factor, we measured the cortical thickness across the whole brain using high-resolution T1-weighted magnetic resonance imaging in 145 first-episode and treatment-naïve patients with schizophrenia and 147 healthy controls. The results showed that, in the patient group, the frontal, temporal, parietal, and cingulate gyri displayed a significant age-related reduction of cortical thickness. In the control group, age-related cortical thickness reduction was mostly located in the frontal, temporal, and cingulate gyri, albeit to a lesser extent. Importantly, relative to healthy controls, patients exhibited a significantly smaller age-related cortical thickness in the anterior cingulate, inferior temporal, and insular gyri in the right hemisphere. These results provide evidence supporting the existence of neurodegenerative processes in schizophrenia and suggest that these processes already occur in the early stage of the illness.
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Affiliation(s)
- Yin Lin
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China.,Department of Psychology, Shenzhen Children's Hospital, Shenzhen, 518038, China
| | - Mingli Li
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yi Zhou
- Department of Radiology, Hospital for Chengdu Office of Tibetan Autonomous Region, Branch Hospital of West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wei Deng
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xiaohong Ma
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Qiang Wang
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Wanjun Guo
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Yinfei Li
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Lijun Jiang
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Xun Hu
- Huaxi Biobank, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Nanyin Zhang
- Department of Biomedical Engineering, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
| | - Tao Li
- Mental Health Centre and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. .,West China Brain Research Centre, West China Hospital, Sichuan University, Chengdu, 610041, China.
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47
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Xie T, Zhang X, Tang X, Zhang H, Yu M, Gong G, Wang X, Evans A, Zhang Z, He Y. Mapping Convergent and Divergent Cortical Thinning Patterns in Patients With Deficit and Nondeficit Schizophrenia. Schizophr Bull 2019; 45:211-221. [PMID: 29272543 PMCID: PMC6293229 DOI: 10.1093/schbul/sbx178] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Deficit schizophrenia (DS) is a homogeneous subtype of schizophrenia characterized by primary and enduring negative symptoms. However, the underlying neuroanatomical substrate of DS remains poorly understood. Here, we collected high-resolution structural magnetic resonance images of 115 participants, including 33 DS patients, 41 nondeficit schizophrenia (NDS) patients, and 41 healthy controls (HCs), and calculated the cortical thickness and surface area for statistical comparisons among the 3 groups. Relative to the control group, both the DS and NDS groups exhibited convergent cortical thinning in the bilateral inferior frontal gyri and the left superior temporal gyrus. The cortical thinning in the right inferior frontal cortex in the patient group was significantly positively correlated with declines of cognitive flexibility and visuospatial memory. Importantly, compared to the NDS group, the DS group exhibited a more widespread cortical thinning pattern, with the most significant differences in the left temporo-parietal junction area. For the surface area measurement, no significant group differences were observed. Collectively, these results highlight the convergent and divergent cortical thinning patterns between patients with DS and NDS, which provide critical insights into the neuroanatomical substrate of DS and improve our understanding of the biological mechanism that contributes to the negative symptoms and cognitive impairments in DS.
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Affiliation(s)
- Teng Xie
- National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China,Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, China,IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Xiangrong Zhang
- Department of Geriatric Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China,Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Xiaowei Tang
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, China
| | - Hongying Zhang
- Department of Radiology, Subei People’s Hospital of Jiangsu Province, Yangzhou University, Yangzhou, China
| | - Miao Yu
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Gaolang Gong
- National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China,Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, China,IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Xiang Wang
- Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, China
| | - Alan Evans
- McConnell Brain Imaging Center, Montreal Neurological Institute, Montreal, Canada
| | - Zhijun Zhang
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Yong He
- National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China,Beijing Key Laboratory of Brain Imaging and Connectomics, Beijing Normal University, Beijing, China,IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China,To whom correspondence should be addressed; National Key Laboratory of Cognitive Neuroscience and Learning, Beijing Key Laboratory of Brain Imaging and Connectomics, IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China. E-mail:
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48
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Neugebauer K, Hammans C, Wensing T, Kumar V, Grodd W, Mevissen L, Sternkopf MA, Novakovic A, Abel T, Habel U, Nickl-Jockschat T. Nerve Growth Factor Serum Levels Are Associated With Regional Gray Matter Volume Differences in Schizophrenia Patients. Front Psychiatry 2019; 10:275. [PMID: 31105606 PMCID: PMC6498747 DOI: 10.3389/fpsyt.2019.00275] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 04/10/2019] [Indexed: 12/24/2022] Open
Abstract
Numerous neuroimaging studies have revealed structural brain abnormalities in schizophrenia patients. There is emerging evidence that dysfunctional nerve growth factor (NGF) signaling may contribute to structural brain alterations found in these patients. In this pilot study, we investigated whether there was a correlation between NGF serum levels and gray matter volume (GMV) in schizophrenia patients. Further, we investigated whether there was an overlap between the correlative findings and cross-sectional GMV differences between schizophrenia patients (n = 18) and healthy controls (n = 19). Serum NGF was significantly correlated to GMV in the left prefrontal lobe, the left midcingulate cortex, and the brainstem in schizophrenia patients. However, we did not find any correlations of NGF serum levels with GMV in healthy controls. Schizophrenia patients showed smaller GMV than healthy controls in brain regions located in the bilateral limbic system, bilateral parietal lobe, bilateral insula, bilateral primary auditory cortex, left frontal lobe, and bilateral occipital regions. In a conjunction analysis, GMV in the left midcingulate cortex (MCC) appears negatively correlated to NGF serum levels in the group of schizophrenia patients and also to be reduced compared to healthy controls. These results suggest an increased vulnerability of schizophrenia patients to changes in NGF levels compared to healthy controls and support a role for NGF signaling in the pathophysiology of schizophrenia. As our pilot study is exploratory in nature, further studies enrolling larger sample sizes will be needed to further corroborate our findings and to investigate the influence of additional covariates.
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Affiliation(s)
- Kristina Neugebauer
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany
| | - Christine Hammans
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany
| | - Tobias Wensing
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany
| | - Vinod Kumar
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany.,Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany
| | - Wolfgang Grodd
- Max-Planck-Institute for Biological Cybernetics, Tübingen, Germany
| | - Lea Mevissen
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany
| | - Melanie A Sternkopf
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany
| | - Ana Novakovic
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany
| | - Ted Abel
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, United States
| | - Ute Habel
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany
| | - Thomas Nickl-Jockschat
- Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.,Jülich-Aachen Research Alliance, Jülich, Germany.,Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, United States.,Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, United States
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49
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White matter abnormalities of the tapetum and their associations with duration of untreated psychosis and symptom severity in first-episode psychosis. Schizophr Res 2018; 201:437-438. [PMID: 29895415 DOI: 10.1016/j.schres.2018.06.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 06/03/2018] [Accepted: 06/03/2018] [Indexed: 11/21/2022]
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50
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Sánchez-Torres AM, Moreno-Izco L, Lorente-Omeñaca R, Cabrera B, Lobo A, González-Pinto AM, Merchán-Naranjo J, Corripio I, Vieta E, de la Serna E, Butjosa A, Contreras F, Sarró S, Mezquida G, Ribeiro M, Bernardo M, Cuesta MJ. Individual trajectories of cognitive performance in first episode psychosis: a 2-year follow-up study. Eur Arch Psychiatry Clin Neurosci 2018; 268:699-711. [PMID: 29164332 DOI: 10.1007/s00406-017-0857-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 11/14/2017] [Indexed: 11/28/2022]
Abstract
Individual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of first episode psychosis (FEP). We aimed to establish whether change in individual trajectories in cognition over 2 years of a sample of 159 FEP patients was reliable and clinically significant, using the reliable change index (RCI) and clinically significant change (CSC) methods. We also studied a sample of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the individual trajectories in the cognitive measures with the regression-based RCI (RCISRB) and the CSC. The RCISRB showed that between 5.4 and 31.2% of the patients showed deterioration patterns, and between 0.6 and 8.8% showed improvement patterns in these tests over time. Patients showing better cognitive profiles according to RCISRB (worsening in zero to two cognitive measures) showed better premorbid, clinical and functional profiles than patients showing deterioration patterns in more than three tests. When combining RCISRB and CSC values, we found that less than 10% of patients showed improvement or deterioration patterns in executive function and attention measures. These results support the view that cognitive impairments are stable over the first 2 years of illness, but also that the analysis of individual trajectories could help to identify a subgroup of patients with particular phenotypes, who may require specific interventions.
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Affiliation(s)
- A M Sánchez-Torres
- Department of Psychiatry, Complejo Hospitalario de Navarra, c/Irunlarrea 3, 31008, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - L Moreno-Izco
- Department of Psychiatry, Complejo Hospitalario de Navarra, c/Irunlarrea 3, 31008, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - R Lorente-Omeñaca
- Department of Psychiatry, Complejo Hospitalario de Navarra, c/Irunlarrea 3, 31008, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - B Cabrera
- Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
| | - A Lobo
- Department of Medicine and Psychiatry, Aragon Institute for Health Research (IIS Aragon), University of Zaragoza, Saragossa, Spain
| | - A M González-Pinto
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- BIOARABA Health Research Institute, OSI Araba University Hospital, Vitoria, Spain
- University of the Basque Country, Vitoria, Spain
| | - J Merchán-Naranjo
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Child and Adolescent Psychiatry Department, School of Medicine, Hospital General Universitario Gregorio Marañón, IISGM, Universidad Complutense, Madrid, Spain
| | - I Corripio
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - E Vieta
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Department of Psychiatry and Psychology, Clinical Institute for the Neurosciences, Hospital Clinic of Barcelona, Catalonia, Spain
- August Pi i Sunyer Institute for Biomedical Research (IDIBAPS), Catalonia, Barcelona, Spain
- Department of Psychiatry and Clinical Psychology, University of Barcelona, Catalonia, Spain
- Department of Psychiatry and Clinical Psychobiology, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - E de la Serna
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic of Barcelona, Barcelona, Spain
| | - A Butjosa
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Parc Sanitari Sant Joan de Déu, Teaching, Research & Innovation Unit, Sant Boi de Llobregat, Barcelona, Spain
- Sant Joan de Déu Research Foundation. Esplugues de Llobregat, Barcelona, Spain
- Department of Personality, Evaluation and Psychological Treatment, Faculty of Psychology, University of Barcelona, Barcelona, Spain
| | - F Contreras
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Psychiatry Department, Bellvitge University Hospital-IDIBELL, L'Hospitalet de Llobregat, Spain
- Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain
| | - S Sarró
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Spain
| | - G Mezquida
- Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain
| | - M Ribeiro
- Department of Psychiatry, Complejo Hospitalario de Navarra, c/Irunlarrea 3, 31008, Pamplona, Spain
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - M Bernardo
- Barcelona Clínic Schizophrenia Unit, Hospital Clínic de Barcelona, Barcelona, Spain
- Network Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid, Spain
- Department of Psychiatry and Clinical Psychobiology, University of Barcelona, IDIBAPS, Barcelona, Spain
| | - M J Cuesta
- Department of Psychiatry, Complejo Hospitalario de Navarra, c/Irunlarrea 3, 31008, Pamplona, Spain.
- IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
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