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Rupert PE, Roalf DR, Prasad KM, Kuo SS, Musket CW, Wood J, Gur RC, Almasy L, Gur RE, Nimgaonkar VL, Pogue-Geile MF. Genetic risk for schizophrenia and brain activation during the Penn Conditional Exclusion Test: A multiplex extended pedigree study. JOURNAL OF PSYCHOPATHOLOGY AND CLINICAL SCIENCE 2025; 134:272-283. [PMID: 40014520 PMCID: PMC11949699 DOI: 10.1037/abn0000973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Individuals with schizophrenia have poorer performance and often differing patterns of brain activation compared to controls on a variety of cognitive tasks, including those that require inhibition of responses and shifting to new responses. This study sought to examine the degree to which performance on a task developed to measure cognitive flexibility, the Penn Conditional Exclusion Test (PCET), and its related brain activation, as assessed on functional magnetic resonance imaging, may reflect schizophrenia genetic risk using an extended pedigree design. A total of 455 participants (27 schizophrenia probands, 170 of their first- to fourth-degree relatives, and 258 unrelated controls) completed similar versions of the PCET, both outside and inside a magnetic resonance imaging scanner. To examine brain activation that may underlie performance, ten regions of interest were identified where activation was significantly correlated with performance. To examine diagnostic specificity, we also investigated genetic correlations between diagnosed major depression and PCET performance and brain activation. Performance was significantly genetically correlated with schizophrenia both out of (Rg = -0.49, p < .001) and in the scanner (Rg = -0.59, p < .001) after false discovery rate correction. In contrast, none of the genetic correlations between schizophrenia and brain activation in the identified regions of interest were significant after false discovery rate correction. Neither behavioral performance nor brain activation measures were significantly genetically correlated with depression. These results suggest that behavioral performance on the PCET is more sensitive (and also specific compared with depression) to schizophrenia genetic risk than is functional magnetic resonance imaging activation that is correlated with performance. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
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Affiliation(s)
| | | | | | - Susan S. Kuo
- University of Pittsburgh, Department of Psychology
- Broad Institute, MIT & Harvard University
| | - Christie W. Musket
- University of Pittsburgh, Department of Psychology
- West Haven VAMC and Yale University
| | - Joel Wood
- University of Pittsburgh, Department of Psychiatry
| | - Ruben C. Gur
- University of Pennsylvania, Department of Psychiatry
| | - Laura Almasy
- University of Pennsylvania, Department of Genetics
| | - Raquel E. Gur
- University of Pennsylvania, Department of Psychiatry
| | | | - Michael F. Pogue-Geile
- University of Pittsburgh, Department of Psychology
- University of Pittsburgh, Department of Psychiatry
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Bodnár AL, Stevens DA, Paez AG, Ultz K, Ross CA, Hua J, Margolis RL. Abnormal arteriolar blood volume measured by 3D inflow-based vascular-space-occupancy (iVASO) MRI and resting-state BOLD fluctuations at 7 T in individuals with recent-onset schizophrenia. PSYCHORADIOLOGY 2025; 5:kkaf001. [PMID: 40182309 PMCID: PMC11966104 DOI: 10.1093/psyrad/kkaf001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/31/2024] [Accepted: 02/06/2025] [Indexed: 04/05/2025]
Abstract
Background We previously reported lower baseline arteriolar cerebral blood volumes (CBVa) in almost all gray matter regions in a cohort of individuals with schizophrenia of varying ages and disease duration. The extent to which decreased CBVa is also present in recent-onset schizophrenia, and how this impacts neurovascular coupling, remains to be determined. In this study, we sought to determine the extent of CBVa deficits in recent-onset schizophrenia and the relationship of CBVa to region-specific resting-state neural activity. Methods Using 7 T MRI, CBVa was measured in 90 regions using 3D inflow-based vascular-space-occupancy (iVASO) imaging in 16 individuals with recent-onset schizophrenia (disease duration: x̄ = 1.18 ± 1.4 years) and 12 age-matched controls. Resting-state functional MRI (rs-fMRI) was used to determine fractional amplitudes of low-frequency fluctuations (fALFF) and intrinsic connectivity (ICC) in spontaneous blood oxygen level-dependent (BOLD) signal. The region-specific relationship between CBVa and fALFF was determined as an index of neurovascular coupling. Results Compared with healthy participants, CBVa was lower in individuals with schizophrenia in almost all brain regions, with a global effect size of 0.23 and regional effect sizes up to 0.41. Individuals with schizophrenia also exhibited lower fALFF diffusely across cortical and subcortical gray matter regions. Ratios of mean regional CBVa to fALFF and ICC were significantly lower in patients in numerous brain regions. Conclusion These findings indicate that early-stage schizophrenia is characterized by widespread microvascular abnormalities and associated resting-state deficits in neural activity, suggesting that abnormalities in neurovascular coupling may contribute to the pathophysiology of schizophrenia.
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Affiliation(s)
- Andor L Bodnár
- Schizoaffective Disorder Precision Medicine Center of Excellence, Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Daniel A Stevens
- Schizoaffective Disorder Precision Medicine Center of Excellence, Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Adrian G Paez
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA
| | - Kia Ultz
- Institutional Review Board, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Christopher A Ross
- Schizoaffective Disorder Precision Medicine Center of Excellence, Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Departments of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Jun Hua
- The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA
| | - Russell L Margolis
- Schizoaffective Disorder Precision Medicine Center of Excellence, Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Wang B, Zhang M, Fan F, Yuan C, Wang Z, Tan Y, Tan S. Subcortical and insula functional connectivity aberrations and clinical implications in first-episode schizophrenia. Asian J Psychiatr 2025; 103:104298. [PMID: 39591757 DOI: 10.1016/j.ajp.2024.104298] [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: 08/31/2024] [Revised: 10/18/2024] [Accepted: 10/27/2024] [Indexed: 11/28/2024]
Abstract
INTRODUCTION Schizophrenia is a complex mental disorder whose pathophysiology remains elusive, particularly in the roles of subcortex. This study aims to explore the role of subcortex and insula and their relationship with symptom changes in first-episode schizophrenia (FES) patients by utilizing machine learning algorithms and functional connectivity (FC). METHODS The study encompasses 261 participants, sourced from two independent samples of FES patients and their matched healthy controls (HC). The discovery dataset includes 77 FES patients at baseline (FES0W) and 77 matched HCs, with the patients undergoing a follow-up scan after eight weeks of antipsychotic treatment (FES8W, N = 34). A validation dataset from another region comprises 47 FES patients and 47 matched HCs. RESULTS Significant differences in subcortical FCs were observed between FES and controls, correlating with symptom severity and symptom changes. Machine learning models were developed to diagnose schizophrenia on an individual basis, achieving a balanced accuracy of 79.55 % across diverse centers. CONCLUSIONS These findings suggest that subcortical connectivity patterns offer potential as biomarkers for schizophrenia, enabling personalized treatment strategies and improving prognosis by facilitating early diagnosis.
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Affiliation(s)
- Bixin Wang
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Meng Zhang
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Fengmei Fan
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Chunyu Yuan
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Zhiren Wang
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Yunlong Tan
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China
| | - Shuping Tan
- Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing 100096, China.
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Wang H, Zhao Q, Zhang Y, Ma J, Lei M, Zhang Z, Xue H, Liu J, Sun Z, Xu J, Zhai Y, Wang Y, Cai M, Zhu W, Liu F. Shared genetic architecture of cortical thickness alterations in major depressive disorder and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2024; 135:111121. [PMID: 39154931 DOI: 10.1016/j.pnpbp.2024.111121] [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: 05/28/2024] [Revised: 07/29/2024] [Accepted: 08/15/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND Major depressive disorder (MDD) and schizophrenia (SCZ) are heritable brain disorders characterized by alterations in cortical thickness. However, the shared genetic basis for cortical thickness changes in these disorders remains unclear. METHODS We conducted a systematic literature search on cortical thickness in MDD and SCZ through PubMed and Web of Science. A coordinate-based meta-analysis was performed to identify cortical thickness changes. Additionally, utilizing summary statistics from the largest genome-wide association studies for depression (Ncase = 268,615, Ncontrol = 667,123) and SCZ (Ncase = 53,386, Ncontrol = 77,258), we explored shared genomic loci using conjunctional false discovery rate (conjFDR) analysis. Transcriptome-neuroimaging association analysis was then employed to identify shared genes associated with cortical thickness alterations, and enrichment analysis was finally carried out to elucidate the biological significance of these genes. RESULTS Our search yielded 34 MDD (Ncase = 1621, Ncontrol = 1507) and 19 SCZ (Ncase = 1170, Ncontrol = 1043) neuroimaging studies for cortical thickness meta-analysis. Specific alterations in the left supplementary motor area were observed in MDD, while SCZ exhibited widespread reductions in various brain regions, particularly in the frontal and temporal areas. The conjFDR approach identified 357 genomic loci jointly associated with MDD and SCZ. Within these loci, 55 genes were found to be associated with cortical thickness alterations in both disorders. Enrichment analysis revealed their involvement in nervous system development, apoptosis, and cell communication. CONCLUSION This study revealed the shared genetic architecture underlying cortical thickness alterations in MDD and SCZ, providing insights into common neurobiological pathways. The identified genes and pathways may serve as potential transdiagnostic markers, informing precision medicine approaches in psychiatric care.
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Affiliation(s)
- He Wang
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Qiyu Zhao
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Yijing Zhang
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Juanwei Ma
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Minghuan Lei
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Zhihui Zhang
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Hui Xue
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Jiawei Liu
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Zuhao Sun
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Jinglei Xu
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Ying Zhai
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Ying Wang
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Mengjing Cai
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Medical Imaging, Henan Provincial People's Hospital & Zhengzhou University People's Hospital, Zhengzhou 450000, China.
| | - Wenshuang Zhu
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China; Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
| | - Feng Liu
- Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin 300052, China.
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Zhang S, Zhao L, Liao A, Li D, Li H, Ouyang L, Chen X, Li Z. Investigating the Shared Genetic Architecture Between Psychiatric Disorders and Executive Function. BIOLOGICAL PSYCHIATRY GLOBAL OPEN SCIENCE 2024; 4:100392. [PMID: 39829962 PMCID: PMC11740799 DOI: 10.1016/j.bpsgos.2024.100392] [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: 07/12/2024] [Revised: 08/23/2024] [Accepted: 08/27/2024] [Indexed: 01/03/2025] Open
Abstract
Background Evidence for widespread comorbidity of executive dysfunctions with psychiatric disorders suggests common mechanisms underlying their pathophysiology. However, the shared genetic architectures between psychiatric disorders and executive function (EF) remain poorly understood. Methods Leveraging large genome-wide association study datasets of European ancestry on bipolar disorder (N = 353,899), major depressive disorder (N = 674,452), and schizophrenia (N = 130,644) from the Psychiatric Genomics Consortium and iPSYCH and a common factor of EF (N = 427,037) from UK Biobank, we systematically investigated the shared genomic architectures between psychiatric disorders and EF with a set of statistical genetic, functional genomic, and gene-level analyses. Results Our study demonstrated substantial genetic overlaps and significant genetic correlations between psychiatric disorders and EF. EF showed an estimated 95.9%, 98.1%, and 99.2% of phenotype-influencing variants, as well as 50, 23, and 130 genomic loci shared with bipolar disorder, major depressive disorder, and schizophrenia, respectively. Single nucleotide polymorphism heritability enrichment suggests that the genetic architecture of psychiatric disorders and EF involves the brain's frontal cortex and prefrontal glutamatergic neurons 1 and 2. Functional genomic analysis of shared variants identified 12 functional regulatory variants that regulate gene expression by affecting the binding affinities of 5 transcription factors. In addition, functional characterization analyses of shared genes revealed potential common biological mechanisms related to synaptic processes and fetal brain development. Conclusions Our findings provide evidence for extensive shared genetic architectures between psychiatric disorders and EF and have valuable implications for future mechanistic investigations and drug development efforts.
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Affiliation(s)
- Sijie Zhang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Linlin Zhao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Aijun Liao
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - David Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Hong Li
- Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lijun Ouyang
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Xiaogang Chen
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- China National Technology Institute on Mental Disorders & Hunan Key Laboratory of Psychiatry and Mental Health, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Zongchang Li
- Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
- China National Technology Institute on Mental Disorders & Hunan Key Laboratory of Psychiatry and Mental Health, Mental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Pollak RM, Sefik E, Aberizk K, Duan K, Espana R, Guest RM, Goldman-Yassen AE, Goines K, Novacek DM, Saulnier CA, Klaiman C, Pulver S, Cubells JF, Burrell TL, Shultz S, Walker EF, Murphy MM, Mulle JG. Beyond IQ: executive function deficits and their relation to functional, clinical, and neuroimaging outcomes in 3q29 deletion syndrome. Psychol Med 2024; 54:1-12. [PMID: 39365000 PMCID: PMC11578917 DOI: 10.1017/s0033291724002320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 07/01/2024] [Accepted: 07/19/2024] [Indexed: 10/05/2024]
Abstract
BACKGROUND 3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described. METHODS We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.5% male, mean age = 14.5 ± 8.3 years). All participants were also evaluated with gold-standard neuropsychiatric and cognitive assessments. High-resolution structural magnetic resonance imaging was performed on a subset of participants (n = 24). RESULTS We found global deficits in EF; individuals with 3q29del scored higher than the population mean on the BRIEF global executive composite (GEC) and all subscales. In total, 81.3% of study subjects (n = 26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC T scores were higher among 3q29del participants with a diagnosis of attention deficit/hyperactivity disorder (ADHD), and BRIEF GEC T scores were associated with schizophrenia spectrum symptoms as measured by the Structured Interview for Psychosis-Risk Syndromes. BRIEF GEC T scores were not associated with cognitive ability. The BRIEF-2 ADHD form accurately (sensitivity = 86.7%) classified individuals with 3q29del based on ADHD diagnosis status. BRIEF GEC T scores were correlated with cerebellar white matter and subregional cerebellar cortex volumes. CONCLUSIONS Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify EF as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.
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Affiliation(s)
- Rebecca M. Pollak
- Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA
| | - Esra Sefik
- Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA
| | - Katrina Aberizk
- Department of Psychology, Emory University, Atlanta, GA, USA
| | - Kuaikuai Duan
- Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA
| | - Roberto Espana
- Department of Psychology, Emory University, Atlanta, GA, USA
| | - Ryan M. Guest
- Department of Psychology, Emory University, Atlanta, GA, USA
| | - Adam E. Goldman-Yassen
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, USA
- Department of Radiology, Children's Healthcare of Atlanta, Atlanta, GA, USA
| | - Katrina Goines
- Department of Psychology, Emory University, Atlanta, GA, USA
| | - Derek M. Novacek
- Desert Pacific Mental Illness Research, Education, and Clinical Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA
- Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA
| | - Celine A. Saulnier
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
- Neurodevelopmental Assessment & Consulting Services, Decatur, GA, USA
| | - Cheryl Klaiman
- Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Stormi Pulver
- Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Joseph F. Cubells
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA
- Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA
| | | | - Sarah Shultz
- Marcus Autism Center, Children's Healthcare of Atlanta & Emory University School of Medicine, Atlanta, GA, USA
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | | | - Melissa M. Murphy
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA
| | - Jennifer G. Mulle
- Center for Advanced Biotechnology and Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA
- Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, USA
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Storozheva ZI, Kirenskaya AV, Samylkin DV, Gruden MA, Sewell RDE. Association of GAD1 gene polymorphism rs3749034 with the information processing and cognitive event-related potentials in schizophrenia patients and healthy subjects. Clin Neurophysiol 2024; 166:142-151. [PMID: 39168087 DOI: 10.1016/j.clinph.2024.08.001] [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: 02/24/2024] [Revised: 08/05/2024] [Accepted: 08/05/2024] [Indexed: 08/23/2024]
Abstract
OBJECTIVE Glutamic acid decarboxylase, an enzyme in GABA biosynthesis, is encoded by the GAD1 gene, the transcriptional activity of which is affected by the rs3749034 polymorphism. The aim was to investigate the effects of rs3749034 on cognitive event-related potentials (P300) in healthy subjects and schizophrenic patients. METHODS Determination of rs3749034 polymorphism was performed in 89 healthy volunteers and 109 schizophrenic patients (males). Two-stimulus oddball task performance and P300 auditory evoked potentials were analyzed and patient symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS An increased frequency of C allele carriers was disclosed in patients. In controls, superior task performance was observed in cytosine-thymine carriers, while a greater P300 amplitude and shorter latency were found in C/C carriers. Analogous effects were found in patients with a disease onset before 25 years of age. Higher N5 and lower P3 and G5 PANSS scales were revealed in C/C homozygotes. CONCLUSIONS The findings substantiate an involvement of GABA-ergic mechanisms in maintaining an optimal excitatory-inhibitory balance and an association of rs3749034 with early-onset disorder and negative symptoms of schizophrenia. SIGNIFICANCE These results are important for understanding underlying mechanisms and the development of evidence-based methods for assessing the risk of schizophrenia.
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Affiliation(s)
| | - Anna V Kirenskaya
- Center of Psychosomatic Medicine and Psychotherapy "Alvian", Moscow, Russia
| | - Denis V Samylkin
- National Medical Research Centre for Psychiatry and Narcology, Moscow, Russia
| | - Marina A Gruden
- P. K. Anokhin Institute of Normal Physiology, Moscow, Russia
| | - Robert D E Sewell
- Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK; Department of Pharmacy, CECOS University, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan.
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Liang J, Chen L, Li Y, Chen Y, Yuan L, Qiu Y, Ma S, Fan F, Cheng Y. Unraveling the Prefrontal Cortex-Basolateral Amygdala Pathway's Role on Schizophrenia's Cognitive Impairments: A Multimodal Study in Patients and Mouse Models. Schizophr Bull 2024; 50:913-923. [PMID: 38811350 PMCID: PMC11283200 DOI: 10.1093/schbul/sbae063] [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] [Indexed: 05/31/2024]
Abstract
BACKGROUND AND HYPOTHESIS This study investigated the role of the medial prefrontal cortex (mPFC)-basolateral amygdala (BLA) pathway in schizophrenia (SCZ)-related cognitive impairments using various techniques. STUDY DESIGN This study utilized clinical scales, magnetic resonance imaging, single-cell RNA sequencing, and optogenetics to investigate the mPFC-BLA pathway in SCZ patients. In the mouse model, 6-week-old methylazoxymethanol acetate-induced mice demonstrated significant cognitive deficits, which were addressed through stereotaxic injections of an adeno-associated viral vector to unveil the neural connection between the mPFC and BLA. STUDY RESULTS Significant disparities in brain volume and neural activity, particularly in the dorsolateral prefrontal cortex (DLPFC) and BLA regions, were found between SCZ patients and healthy controls. Additionally, we observed correlations indicating that reduced volumes of the DLPFC and BLA were associated with lower cognitive function scores. Activation of the mPFC-BLA pathway notably improved cognitive performance in the SCZ model mice, with the targeting of excitatory or inhibitory neurons alone failing to replicate this effect. Single-cell transcriptomic profiling revealed gene expression differences in excitatory and inhibitory neurons in the BLA of SCZ model mice. Notably, genes differentially expressed in the BLA of these model mice were also found in the blood exosomes of SCZ patients. CONCLUSIONS Our research provides a comprehensive understanding of the role of the PFC-BLA pathway in SCZ, underscoring its significance in cognitive impairment and offering novel diagnostic and therapeutic avenues. Additionally, our research highlights the potential of blood exosomal mRNAs as noninvasive biomarkers for SCZ diagnosis, underscoring the clinical feasibility and utility of this method.
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Affiliation(s)
- Jiaquan Liang
- Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
- The Third People’s Hospital of Foshan, Guangdong, China
| | - Lei Chen
- Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - Yongbiao Li
- Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - Yuewen Chen
- Chinese Academy of Sciences Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Translational Research for Brain Diseases, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen–Hong Kong Institute of Brain Science—Shenzhen Fundamental Research Institutions, Shenzhen, China
- Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, China
| | - Lin Yuan
- Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, China
| | - Yue Qiu
- Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, China
| | - Shuangshuang Ma
- Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, China
| | - Fangcheng Fan
- Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
| | - Yong Cheng
- Key Laboratory of Ethnomedicine of Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, China
- Institute of National Security, Minzu University of China, Beijing, China
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Mana L, Schwartz-Pallejà M, Vila-Vidal M, Deco G. Overview on cognitive impairment in psychotic disorders: From impaired microcircuits to dysconnectivity. Schizophr Res 2024; 269:132-143. [PMID: 38788432 DOI: 10.1016/j.schres.2024.05.008] [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: 01/15/2024] [Revised: 05/09/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024]
Abstract
Schizophrenia's cognitive deficits, often overshadowed by positive symptoms, significantly contribute to the disorder's morbidity. Increasing attention highlights these deficits as reflections of neural circuit dysfunction across various cortical regions. Numerous connectivity alterations linked to cognitive symptoms in psychotic disorders have been reported, both at the macroscopic and microscopic level, emphasizing the potential role of plasticity and microcircuits impairment during development and later stages. However, the heterogeneous clinical presentation of cognitive impairment and diverse connectivity findings pose challenges in summarizing them into a cohesive picture. This review aims to synthesize major cognitive alterations, recent insights into network structural and functional connectivity changes and proposed mechanisms and microcircuit alterations underpinning these symptoms, particularly focusing on neurodevelopmental impairment, E/I balance, and sleep disturbances. Finally, we will also comment on some of the most recent and promising therapeutic approaches that aim to target these mechanisms to address cognitive symptoms. Through this comprehensive exploration, we strive to provide an updated and nuanced overview of the multiscale connectivity impairment underlying cognitive impairment in psychotic disorders.
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Affiliation(s)
- L Mana
- Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Roc Boronat 138, Barcelona 08018, Spain.
| | - M Schwartz-Pallejà
- Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Roc Boronat 138, Barcelona 08018, Spain; Department of Experimental and Health Science, Universitat Pompeu Fabra, Roc Boronat 138, Barcelona 08018, Spain; Eurecat, Technology Center of Catalonia, Multimedia Technologies, Barcelona, Spain.
| | - M Vila-Vidal
- Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Roc Boronat 138, Barcelona 08018, Spain; Computational Biology and Complex Systems Group, Department of Physics, Universitat Politècnica de Catalunya, Barcelona, Spain.
| | - G Deco
- Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Roc Boronat 138, Barcelona 08018, Spain; Institució Catalana de la Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona 08010, Spain.
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Angelopoulou E, Koros C, Hatzimanolis A, Stefanis L, Scarmeas N, Papageorgiou SG. Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease. Int J Mol Sci 2024; 25:2645. [PMID: 38473892 PMCID: PMC10931648 DOI: 10.3390/ijms25052645] [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: 01/08/2024] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 03/14/2024] Open
Abstract
The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.
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Affiliation(s)
- Efthalia Angelopoulou
- 1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (E.A.); (L.S.); (N.S.); (S.G.P.)
| | - Christos Koros
- 1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (E.A.); (L.S.); (N.S.); (S.G.P.)
| | - Alexandros Hatzimanolis
- 1st Department of Psychiatry, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece;
| | - Leonidas Stefanis
- 1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (E.A.); (L.S.); (N.S.); (S.G.P.)
| | - Nikolaos Scarmeas
- 1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (E.A.); (L.S.); (N.S.); (S.G.P.)
- Department of Neurology, Columbia University, New York, NY 10032, USA
| | - Sokratis G. Papageorgiou
- 1st Department of Neurology, Aiginition University Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece; (E.A.); (L.S.); (N.S.); (S.G.P.)
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He K, Hua Q, Li Q, Zhang Y, Yao X, Yang Y, Xu W, Sun J, Wang L, Wang A, Ji GJ, Wang K. Abnormal interhemispheric functional cooperation in schizophrenia follows the neurotransmitter profiles. J Psychiatry Neurosci 2023; 48:E452-E460. [PMID: 38123242 PMCID: PMC10743641 DOI: 10.1503/jpn.230037] [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: 03/02/2023] [Revised: 06/26/2023] [Accepted: 09/05/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Interhemispheric cooperation is one of the most prominent functional architectures of the human brain. In patients with schizophrenia, interhemispheric cooperation deficits have been reported using increasingly powerful neurobehavioural and neuroimaging measures. However, these methods rely in part on the assumption of anatomic symmetry between hemispheres. In the present study, we explored interhemispheric cooperation deficits in schizophrenia using a newly developed index, connectivity between functionally homotopic voxels (CFH), which is unbiased by hemispheric asymmetry. METHODS Patients with schizophrenia and age- and sexmatched healthy controls underwent multimodal MRI, and whole-brain CFH maps were constructed for comparison between groups. We examined the correlations of differing CFH values between the schizophrenia and control groups using various neurotransmitter receptor and transporter densities. RESULTS We included 86 patients with schizophrenia and 86 matched controls in our analysis. Patients with schizophrenia showed significantly lower CFH values in the frontal lobes, left postcentral gyrus and right inferior temporal gyrus, and significantly greater CFH values in the right caudate nucleus than healthy controls. Moreover, the differing CFH values in patients with schizophrenia were significantly correlated with positive symptom score and illness duration. Functional connectivity within frontal lobes was significantly reduced at the voxel cluster level compared with healthy controls. Finally, the abnormal CFH map of patients with schizophrenia was spatially associated with the densities of the dopamine D1 and D2 receptors, fluorodopa, dopamine transporter, serotonin transporter and acetylcholine transporter. CONCLUSION Regional abnormalities in interhemispheric cooperation may contribute to the clinical symptoms of schizophrenia. These CFH abnormalities may be associated with dysfunction in neurotransmitter systems strongly implicated in schizophrenia.
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Affiliation(s)
- Kongliang He
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Qiang Hua
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Qianqian Li
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Yan Zhang
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Xiaoqing Yao
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Yinian Yang
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Wenqiang Xu
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Jinmei Sun
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Lu Wang
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Anzhen Wang
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Gong-Jun Ji
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
| | - Kai Wang
- From the Affiliated Psychological Hospital of Anhui Medical University, Hefei, China (He, A. Wang); the Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, China (He, Hua, Yao, Sun, L. Wang, Ji, K. Wang); the School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, China (He, Zhang, Yang, Xu, A. Wang, Ji, K. Wang); the Hefei Fourth People's Hospital, Hefei, China (He, A. Wang); the Anhui Mental Health Center, Hefei, China (He, A. Wang); the Department of Psychology and Sleep Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, China (Li); the Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Collaborative Innovation Centre of Neuropsychiatric Disorder and Mental Health, Hefei, China (Hua, Li, Zhang, Yang, Xu, Sun, L. Wang, Ji, K. Wang); the Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China (K. Wang); and the Anhui Institute of Translational Medicine, Hefei, China (K. Wang)
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Ye J, Sun H, Gao S, Dadashkarimi J, Rosenblatt M, Rodriguez RX, Mehta S, Jiang R, Noble S, Westwater ML, Scheinost D. Altered Brain Dynamics Across Bipolar Disorder and Schizophrenia During Rest and Task Switching Revealed by Overlapping Brain States. Biol Psychiatry 2023; 94:580-590. [PMID: 37031780 PMCID: PMC10524212 DOI: 10.1016/j.biopsych.2023.03.024] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 03/27/2023] [Accepted: 03/30/2023] [Indexed: 04/11/2023]
Abstract
BACKGROUND Individuals with bipolar disorder (BD) and schizophrenia (SCZ) show aberrant brain dynamics (i.e., altered recruitment or traversal through different brain states over time). Existing investigations of brain dynamics typically assume that one dominant brain state characterizes each time point. However, as multiple brain states likely are engaged at any given moment, this approach can obscure alterations in less prominent but critical brain states. Here, we examined brain dynamics in BD and SCZ by implementing a novel framework that simultaneously assessed the engagement of multiple brain states. METHODS Four recurring brain states were identified by applying nonlinear manifold learning and k-means clustering to the Human Connectome Project task-based functional magnetic resonance imaging data. We then assessed moment-to-moment state engagement in 2 independent samples of healthy control participants and patients with BD or SCZ using resting-state (N = 336) or task-based (N = 217) functional magnetic resonance imaging data. Relative state engagement and state engagement variability were extracted and compared across groups using multivariate analysis of covariance, controlling for site, medication, age, and sex. RESULTS Our framework identified dynamic alterations in BD and SCZ, while a state discretization approach revealed no significant group differences. Participants with BD or SCZ showed reduced state engagement variability, but not relative state engagement, across multiple brain states during resting-state and task-based functional magnetic resonance imaging. We found decreased state engagement variability in older participants and preliminary evidence suggesting an association with avolition. CONCLUSIONS Assessing multiple brain states simultaneously can reflect the complexity of aberrant brain dynamics in BD and SCZ, providing a more comprehensive understanding of the neural mechanisms underpinning these conditions.
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Affiliation(s)
- Jean Ye
- Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut.
| | - Huili Sun
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut
| | - Siyuan Gao
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut
| | | | - Matthew Rosenblatt
- Department of Biomedical Engineering, Yale University, New Haven, Connecticut
| | | | - Saloni Mehta
- Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Rongtao Jiang
- Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Stephanie Noble
- Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Margaret L Westwater
- Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut
| | - Dustin Scheinost
- Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut; Department of Biomedical Engineering, Yale University, New Haven, Connecticut; Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut; Child Study Center, Yale School of Medicine, New Haven, Connecticut; Department of Statistics and Data Science, Yale University, New Haven, Connecticut
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13
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Horowitz-Kraus T, Randell K, Morag I. Neurobiological perspective on the development of executive functions. Acta Paediatr 2023; 112:1860-1864. [PMID: 37338188 DOI: 10.1111/apa.16883] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 06/14/2023] [Accepted: 06/19/2023] [Indexed: 06/21/2023]
Abstract
Executive functions are a set of top-down cognitive processes necessary for emotional self-regulation and goal-directed behaviour supporting, among others, academic abilities. Premature infants are at high risk for subsequent cognitive, psychosocial, or behavioural problems even in the absence of medical complications and in spite of normal brain imaging. Given that this is a sensitive period of brain growth and maturation, these factors may place preterm infants at high risk for executive function dysfunction, disrupted long-term development, and lower academic achievements. Therefore, careful attention to interventions at this age is essential for intact executive functions and academic development.
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Affiliation(s)
- Tzipi Horowitz-Kraus
- Educational Neuroimaging Group, Faculty of Education in Science and Technology and Faculty of Biomedical Engineering, The Technion, Haifa, Israel
- Kennedy Krieger Institute, Baltimore, Maryland, USA
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Iris Morag
- Department of Pediatrics, Shamir Medical Center affiliated to Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
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Zheng G, Zhou Y, Zhou J, Liang S, Li X, Xu C, Xie G, Liang J. Abnormalities of the Amygdala in schizophrenia: a real world study. BMC Psychiatry 2023; 23:615. [PMID: 37608255 PMCID: PMC10463851 DOI: 10.1186/s12888-023-05031-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/17/2023] [Indexed: 08/24/2023] Open
Abstract
BACKGROUND Amygdala plays an important role in schizophrenia (SC), but its mechanisms are still unclear. Therefore, we investigated the relationship between the resting-state magnetic resonance imaging (rsMRI) signals of the amygdala and cognitive functions, providing references for future research in this area. METHODS We collected 40 drug-naïve SC patients and 33 healthy controls (HC) from the Third People's Hospital of Foshan. We used rsMRI and the automatic segmentation tool to extract the structural volume and local neural activity values of the amygdala and conducted Pearson correlation analysis with the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. Finally, we compared the clinical data, as well as the volume and functional changes of the amygdala in SC patients before and after treatment. RESULTS Compared with HC, SC had widespread cognitive impairments, significant abnormalities in left amygdala function, while the reduction in volume of SC was not significant. Further Pearson correlation analysis with Bonferroni correction showed that only Immediate memory (learning) was significantly negatively correlated with fractional amplitude of low-frequency fluctuation (FALFF, r = -0.343, p = 0.001, p' = 0.014 (Bonferroni correction)). When compared and analyzed the data difference of SC before and after treatment, we found that immediate memory and delayed memory of SC showed varying degrees of recovery after treatment (tlearning = -2.641, plearning = 0.011; tstory memory = -3.349, pstory memory = 0.001; tlist recall = -2.071, plist recall = 0.043; tstory recall = -2.424, pstory recall = 0.018). But the brain structure and function did not recover. CONCLUSION There was significant dysfunction in the amygdala in SC, and after conventional treatment, the function of the amygdala did not improve with the improvement of clinical symptoms and cognitive function.
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Affiliation(s)
- Guangen Zheng
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China
- Nanhai Public Health Hospital of Foshan City, Guangdong, People's Republic of China
| | - Yang Zhou
- Nanhai Public Health Hospital of Foshan City, Guangdong, People's Republic of China
| | - Jieming Zhou
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China
| | - Shuting Liang
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China
| | - Xiaoling Li
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China
| | - Caixia Xu
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China
| | - Guojun Xie
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China.
| | - Jiaquan Liang
- Department of Psychiatry, The Third People's Hospital of Foshan, Guangdong, People's Republic of China.
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15
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Jo YT, Lee JS, Park J, Lee J, Joo YH. Linguistic anomalies observed in the Sentence Completion Test in patients with schizophrenia. Cogn Neuropsychiatry 2023; 28:226-236. [PMID: 37167542 DOI: 10.1080/13546805.2023.2209313] [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: 05/13/2023]
Abstract
BACKGROUND Schizophrenia is a chronic, debilitating disorder characterised by distorted thinking, perceptions, behaviours, and even language impairments. We investigated the linguistic anomalies in Korean schizophrenia patients compared to non-psychotic psychiatric controls to determine whether the linguistic anomalies in English speakers with schizophrenia were replicated in Korean speakers. METHODS Thirty-four schizophrenia patients and 70 non-psychotic psychiatric controls were included in this study. The SCT was utilised as the text data for analysis. For linguistic analysis, we evaluated texts regarding semantics and syntax. We separately counted the number of semantic or syntactic errors in the written texts of study participants and compared them between patients and controls. RESULTS Schizophrenia patients showed significantly more semantic errors (p < .001) and syntactic errors (p < .001) per 1,000 characters than non-psychotic psychiatric controls. Specifically, inappropriate word or syntactic component selection is noticeable in schizophrenia patients. These differences were still significant after adjusting for general intelligence measured by the K-WAIS-IV. CONCLUSION Schizophrenia patients showed both semantic and syntactic errors in written language. Moreover, these errors seemed to be partly independent of general intelligence. Notably, patients showed a noticeable number of syntactic errors. Further investigation into the language of patients with schizophrenia and schizophrenia-spectrum disorders is required.
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Affiliation(s)
- Young Tak Jo
- Department of Psychiatry, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
| | - Ji Soo Lee
- Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jaiyoung Park
- Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jungsun Lee
- Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yeon Ho Joo
- Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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16
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Rubinstein DY, Eisenberg DP, Carver FW, Holroyd T, Apud JA, Coppola R, Berman KF. Spatiotemporal Alterations in Working Memory-Related Beta Band Neuromagnetic Activity of Patients With Schizophrenia On and Off Antipsychotic Medication: Investigation With MEG. Schizophr Bull 2023; 49:669-678. [PMID: 36772948 PMCID: PMC10154700 DOI: 10.1093/schbul/sbac178] [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] [Indexed: 02/12/2023]
Abstract
BACKGROUND AND HYPOTHESIS We used the uniquely high combined spatial and temporal resolution of magnetoencephalography to characterize working memory (WM)-related modulation of beta band activity in neuroleptic-free patients with schizophrenia in comparison to a large sample of performance-matched healthy controls. We also tested for effects of antipsychotic medication on identified differences in these same patients. STUDY DESIGN Inpatients with schizophrenia (n = 21) or psychotic disorder not otherwise specified (n = 4) completed N-back and control tasks during magnetoencephalography while on placebo and during antipsychotic medication treatment, in a blinded, randomized, counterbalanced manner. Healthy, performance-matched controls (N = 100) completed the same tasks. WM-related neural activation was estimated as beta band (14-30 Hz) desynchronization throughout the brain in successive 400 ms time windows. Voxel-wise statistical comparisons were performed between controls and patients while off-medication at each time window. Significant clusters resulting from this between-groups analysis were then used as regions-of-interest, the activations of which were compared between on- and off-medication conditions in patients. STUDY RESULTS Controls showed beta-band desynchronization (activation) of a fronto-parietal network immediately preceding correct button press responses-the time associated with WM updating and task execution. Altered activation in medication-free patients occurred largely during this time, in prefrontal, parietal, and visual cortices. Medication altered patients' neural responses such that the activation time courses in these regions-of-interest more closely resembled those of controls. CONCLUSIONS These findings demonstrate that WM-related beta band alterations in schizophrenia are time-specific and associated with neural systems targeted by antipsychotic medications. Future studies may investigate this association by examining its potential neurochemical basis.
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Affiliation(s)
- Daniel Y Rubinstein
- Section on Integrative Neuroimaging, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
- Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
| | - Daniel P Eisenberg
- Section on Integrative Neuroimaging, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
- Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
| | | | - Tom Holroyd
- MEG Core Facility, NIH, DHHS, Bethesda, MD, USA
| | - Jose A Apud
- Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
| | - Richard Coppola
- Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
- MEG Core Facility, NIH, DHHS, Bethesda, MD, USA
| | - Karen F Berman
- Section on Integrative Neuroimaging, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
- Clinical and Translational Neuroscience Branch, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA
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17
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No training effects of top-down controlled response inhibition by practicing on the stop-signal task. Acta Psychol (Amst) 2023; 235:103878. [PMID: 36913850 DOI: 10.1016/j.actpsy.2023.103878] [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: 08/28/2022] [Revised: 01/25/2023] [Accepted: 03/06/2023] [Indexed: 03/13/2023] Open
Abstract
The aim of the current study is to examine if the top-down controlled response inhibition on a stop-signal task (SST) can be trained. Results from previous studies have been equivocal, possibly because signal-response combinations are often not varied across training and test phases, allowing bottom-up signal-response associations to be formed that may improve response inhibition. The current study compared the response inhibition on the SST in a pre-test and post-test in an experimental group (EG) and control group (CG). In between tests, the EG received ten training sessions on the SST with varying signal-response combinations that were also different from the combinations in the test phase. The CG received ten training sessions on the choice reaction time task. Results failed to reveal a decrease in stop-signal reaction time (SSRT) during and after training, with Bayesian analyses revealing anecdotal and substantial evidence for the null hypothesis during and after training, respectively. Yet, the EG did show smaller go reaction times (Go_RT) and stop signal delays (SSD) after training. The results indicate that the top-down controlled response inhibition is difficult or impossible to improve.
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18
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Arnautovska U, Kesby JP, Korman N, Rebar AL, Chapman J, Warren N, Rossell SL, Dark FL, Siskind D. Biopsychology of Physical Activity in People with Schizophrenia: An Integrative Perspective on Barriers and Intervention Strategies. Neuropsychiatr Dis Treat 2022; 18:2917-2926. [PMID: 36544549 PMCID: PMC9763049 DOI: 10.2147/ndt.s393775] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 12/02/2022] [Indexed: 12/23/2022] Open
Abstract
People with severe mental illness such as schizophrenia experience high physical comorbidity, leading to a 15-20-year mortality gap compared with the general population. Lifestyle behaviours such as physical activity (PA) play important roles in the quest to bridge this gap. Interventions to increase PA engagement in this population have potential to be efficacious; however, their effectiveness can be hindered by low participant engagement, including low adherence and high drop-out, and by implementation of interventions that are not designed to compensate for the cognitive and motivational impairments characteristic for this group. Moreover, and importantly, the negative symptoms of schizophrenia are associated with neurobiological changes in the brain, which-based on principles of biopsychology-can contribute to poor motivation and impaired decision-making processes and behavioural maintenance. To increase PA levels in people with schizophrenia, better understanding of these neurological changes that impact PA engagement is needed. This has the potential to inform the design of interventions that, through enhancement of motivation, could effectively increase PA levels in this specific population. Incorporating strategies that address the dopamine dysregulation associated with schizophrenia, such as boosting the role of reward and self-determined motivation, may improve long-term PA maintenance, leading to habitual PA. Consideration of motivation and behavioural maintenance is also needed to impart health benefits such as prevention of chronic disease, which is associated with currently low PA levels in this high metabolic risk population. Taking a biopsychological perspective, we outline the neural pathways involved in motivation that are impacted by schizophrenia and propose strategies for promoting motivation for and PA engagement from adoption to habit formation.
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Affiliation(s)
- Urska Arnautovska
- Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia
- Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia
| | - James P Kesby
- Centre for Mental Health, Griffith University, Nathan, QLD, Australia
- Queensland Centre for Mental Health Research, Wacol, QLD, 4076, Australia
| | - Nicole Korman
- Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia
- Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia
| | - Amanda L Rebar
- Motivation of Health Behaviours Lab, Appleton Institute, School of Health, Medical, and Applied Sciences; Central Queensland University, Rockhampton, QLD, Australia
| | - Justin Chapman
- Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia
- Centre for Mental Health, Griffith University, Nathan, QLD, Australia
| | - Nicola Warren
- Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia
- Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia
| | - Susan L Rossell
- Centre for Mental Health, School of Health Sciences, Swinburne University of Technology, Hawthorn, VIC, Australia
- Psychiatry, St Vincent’s Hospital Melbourne, Fitzroy, VIC, Australia
| | - Frances L Dark
- Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia
- Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia
| | - Dan Siskind
- Faculty of Medicine, The University of Queensland, Woolloongabba, QLD, Australia
- Metro South Addictions and Mental Health Service, Woolloongabba, QLD, Australia
- Queensland Centre for Mental Health Research, Wacol, QLD, 4076, Australia
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19
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Functional connectivity directionality between large-scale resting-state networks across typical and non-typical trajectories in children and adolescence. PLoS One 2022; 17:e0276221. [PMID: 36454744 PMCID: PMC9714732 DOI: 10.1371/journal.pone.0276221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 10/04/2022] [Indexed: 12/02/2022] Open
Abstract
Mental disorders often emerge during adolescence and have been associated with age-related differences in connection strengths of brain networks (static functional connectivity), manifesting in non-typical trajectories of brain development. However, little is known about the direction of information flow (directed functional connectivity) in this period of functional brain progression. We employed dynamic graphical models (DGM) to estimate directed functional connectivity from resting state functional magnetic resonance imaging data on 1143 participants, aged 6 to 17 years from the healthy brain network (HBN) sample. We tested for effects of age, sex, cognitive abilities and psychopathology on estimates of direction flow. Across participants, we show a pattern of reciprocal information flow between visual-medial and visual-lateral connections, in line with findings in adults. Investigating directed connectivity patterns between networks, we observed a positive association for age and direction flow from the cerebellar to the auditory network, and for the auditory to the sensorimotor network. Further, higher cognitive abilities were linked to lower information flow from the visual occipital to the default mode network. Additionally, examining the degree networks overall send and receive information to each other, we identified age-related effects implicating the right frontoparietal and sensorimotor network. However, we did not find any associations with psychopathology. Our results suggest that the directed functional connectivity of large-scale resting-state brain networks is sensitive to age and cognition during adolescence, warranting further studies that may explore directed relationships at rest and trajectories in more fine-grained network parcellations and in different populations.
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20
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Chang X, Jia X, Wang Y, Dong D. Alterations of cerebellar white matter integrity and associations with cognitive impairments in schizophrenia. Front Psychiatry 2022; 13:993866. [PMID: 36226106 PMCID: PMC9549145 DOI: 10.3389/fpsyt.2022.993866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022] Open
Abstract
"Cognitive dysmetria" theory of schizophrenia (SZ) has highlighted that the cerebellum plays a critical role in understanding the pathogenesis and cognitive impairment in SZ. Despite some studies have reported the structural disruption of the cerebellum in SZ using whole brain approach, specific focus on the voxel-wise changes of cerebellar WM microstructure and its associations with cognition impairments in SZ were less investigated. To further explore the voxel-wise structural disruption of the cerebellum in SZ, the present study comprehensively examined volume and diffusion features of cerebellar white matter in SZ at the voxel level (42 SZ vs. 52 controls) and correlated the observed alterations with the cognitive impairments measured by MATRICS Consensus Cognitive Battery. Combing voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) methods, we found, compared to healthy controls (HCs), SZ patients did not show significant alteration in voxel-level cerebellar white matter (WM) volume and tract-wise and skeletonized DTI features. In voxel-wise DTI features of cerebellar peduncles, compared to HCs, SZ patients showed decreased fractional anisotropy and increased radial diffusivity mainly located in left middle cerebellar peduncles (MCP) and inferior cerebellar peduncles (ICP). Interestingly, these alterations were correlated with overall composite and different cognitive domain (including processing speed, working memory, and attention vigilance) in HCs but not in SZ patients. The present findings suggested that the voxel-wise WM integrity analysis might be a more sensitive way to investigate the cerebellar structural abnormalities in SZ patients. Correlation results suggested that inferior and MCP may be a crucial neurobiological substrate of cognition impairments in SZ, thus adding the evidence for taking the cerebellum as a novel therapeutic target for cognitive impairments in SZ patients.
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Affiliation(s)
- Xuebin Chang
- Department of Information Sciences, School of Mathematics and Statistics, Xi’an Jiaotong University, Xi’an, China
| | - Xiaoyan Jia
- The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China
| | - Yulin Wang
- Key Laboratory of Cognition and Personality, Southwest University (SWU), Ministry of Education, Chongqing, China
- Faculty of Psychology, Southwest University (SWU), Chongqing, China
| | - Debo Dong
- Key Laboratory of Cognition and Personality, Southwest University (SWU), Ministry of Education, Chongqing, China
- Faculty of Psychology, Southwest University (SWU), Chongqing, China
- Institute of Neuroscience and Medicine, Brain and Behaviour (INM-7), Research Centre Jülich, Jülich, Germany
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21
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Karcher NR, Merchant J, Pine J, Kilciksiz CM. Cognitive Dysfunction as a Risk Factor for Psychosis. Curr Top Behav Neurosci 2022; 63:173-203. [PMID: 35989398 DOI: 10.1007/7854_2022_387] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The current chapter summarizes recent evidence for cognition as a risk factor for the development of psychosis, including the range of cognitive impairments that exist across the spectrum of psychosis risk symptoms. The chapter examines several possible theories linking cognitive deficits with the development of psychotic symptoms, including evidence that cognitive deficits may be an intermediate risk factor linking genetic and/or neural metrics to psychosis spectrum symptoms. Although there is not strong evidence for unique cognitive markers associated specifically with psychosis compared to other forms of psychopathology, psychotic disorders are generally associated with the greatest severity of cognitive deficits. Cognitive deficits precede the development of psychotic symptoms and may be detectable as early as childhood. Across the psychosis spectrum, both the presence and severity of psychotic symptoms are associated with mild to moderate impairments across cognitive domains, perhaps most consistently for language, cognitive control, and working memory domains. Research generally indicates the size of these cognitive impairments worsens as psychosis symptom severity increases. The chapter points out areas of unclarity and unanswered questions in each of these areas, including regarding the mechanisms contributing to the association between cognition and psychosis, the timing of deficits, and whether any cognitive systems can be identified that function as specific predictors of psychosis risk symptoms.
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Affiliation(s)
- Nicole R Karcher
- Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
| | - Jaisal Merchant
- Department of Brain and Psychological Sciences, Washington University in St. Louis, St. Louis, MO, USA
| | - Jacob Pine
- Department of Brain and Psychological Sciences, Washington University in St. Louis, St. Louis, MO, USA
| | - Can Misel Kilciksiz
- Department of Psychiatry, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA
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22
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Lipina T, Men X, Blundell M, Salahpour A, Ramsey AJ. Abnormal sensory perception masks behavioral performance of Grin1 knockdown mice. GENES, BRAIN, AND BEHAVIOR 2022; 21:e12825. [PMID: 35705513 PMCID: PMC9744498 DOI: 10.1111/gbb.12825] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 05/30/2022] [Accepted: 05/31/2022] [Indexed: 11/28/2022]
Abstract
The development and function of sensory systems require intact glutamatergic neurotransmission. Changes in touch sensation and vision are common symptoms in autism spectrum disorders, where altered glutamatergic neurotransmission is strongly implicated. Further, cortical visual impairment is a frequent symptom of GRIN disorder, a rare genetic neurodevelopmental disorder caused by pathogenic variants of GRIN genes that encode NMDA receptors. We asked if Grin1 knockdown mice (Grin1KD), as a model of GRIN disorder, had visual impairments resulting from NMDA receptor deficiency. We discovered that Grin1KD mice had deficient visual depth perception in the visual cliff test. Since Grin1KD mice are known to display robust changes in measures of learning, memory, and emotionality, we asked whether deficits in these higher-level processes could be partly explained by their visual impairment. By changing the experimental conditions to improve visual signals, we observed significant improvements in the performance of Grin1KD mice in tests that measure spatial memory, executive function, and anxiety. We went further and found destabilization of the outer segment of retina together with the deficient number and size of Meissner corpuscles (mechanical sensor) in the hind paw of Grin1KD mice. Overall, our findings suggest that abnormal sensory perception can mask the expression of emotional, motivational and cognitive behavior of Grin1KD mice. This study demonstrates new methods to adapt routine behavioral paradigms to reveal the contribution of vision and other sensory modalities in cognitive performance.
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Affiliation(s)
- Tatiana Lipina
- Department of Pharmacology & ToxicologyUniversity of TorontoTorontoOntarioCanada
| | - Xiaoyu Men
- Department of Pharmacology & ToxicologyUniversity of TorontoTorontoOntarioCanada
| | - Matisse Blundell
- Department of PhysiologyUniversity of TorontoTorontoOntarioCanada
| | - Ali Salahpour
- Department of Pharmacology & ToxicologyUniversity of TorontoTorontoOntarioCanada
| | - Amy J. Ramsey
- Department of Pharmacology & ToxicologyUniversity of TorontoTorontoOntarioCanada
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23
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Adam Yaple Z, Tolomeo S, Yu R. Spatial and chronic differences in neural activity in medicated and unmedicated schizophrenia patients. Neuroimage Clin 2022; 35:103029. [PMID: 35569228 PMCID: PMC9112098 DOI: 10.1016/j.nicl.2022.103029] [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: 12/01/2021] [Revised: 04/10/2022] [Accepted: 04/28/2022] [Indexed: 11/07/2022]
Abstract
The medicated schizophrenia group yielded concordant activity among three right lateralized frontal clusters and a left lateralized parietal cluster. The unmedicated schizophrenia group yielded concordant activity among right lateralized frontal-parietal regions. A neural compensatory mechanism in schizophrenia. A major caveat with investigations on schizophrenic patients is the difficulty to control for medication usage across samples as disease-related neural differences may be confounded by medication usage. Following a thorough literature search (632 records identified), we included 37 studies with a total of 740 medicated schizophrenia patients and 367 unmedicated schizophrenia patients. Here, we perform several meta-analyses to assess the neurofunctional differences between medicated and unmedicated schizophrenic patients across fMRI studies to determine systematic regions associated with medication usage. Several clusters identified by the meta-analysis on the medicated group include three right lateralized frontal clusters and a left lateralized parietal cluster, whereas the unmedicated group yielded concordant activity among right lateralized frontal-parietal regions. We further explored the prevalence of activity within these regions across illness duration and task type. These findings suggest a neural compensatory mechanism across these regions both spatially and chronically, offering new insight into the spatial and temporal dynamic neural differences among medicated and unmedicated schizophrenia patients.
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Affiliation(s)
| | - Serenella Tolomeo
- Social and Cognitive Computing Department, Institute of High Performance Computing, Agency for Science, Technology and Research, Singapore, Singapore
| | - Rongjun Yu
- Department of Management, Hong Kong Baptist University, Hong Kong, China; Department of Sport, Physical Education and Health, Hong Kong Baptist University, Hong Kong, China; Department of Physics, Hong Kong Baptist University, Hong Kong, China.
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24
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Rodríguez-Toscano E, Martínez K, Fraguas D, Janssen J, Pina-Camacho L, Arias B, Vieta E, Mezquida G, Amoretti S, Bernardo M, Castro-Fornieles J, Cuesta-Zorita MJ, Lobo A, González-Pinto A, Collado IC, Mané A, Arango C, Parellada M. Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val 158Met polymorphism in first episode psychosis. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2022; 15:74-87. [PMID: 35840287 DOI: 10.1016/j.rpsmen.2022.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/06/2021] [Indexed: 06/15/2023]
Abstract
INTRODUCTION Core dysfunctions proposed for psychotic disorders include prefrontal cortex (PFC) dopaminergic hypoactivity, executive function (EF) deficits and reduced gray matter in the PFC. The Val variant of COMT Val158Met polymorphism is associated with reduced dopaminergic signaling in the PFC. However, it is unclear how COMT Val158Met modulates PFC gray matter reduction, EF deficits and symptom severity at the time of the first psychotic episode. METHODS The effect of COMT on both EF performance and prefrontal volume (PFC-VOL) was tested in 158 first episode psychosis (FEP) patients and 141 healthy controls (HC) matched for age (range 9-35 years), sex, ethnicity, handedness and COMT Val158Met distribution. EF and PFC-VOL were compared between FEP and HC groups within each polymorphism status (Met/Met versus Val carriers) to assess whether COMT influenced diagnostic differences. Next, correlations between PFC-VOL and EF performance were computed, as well as between both variables and other clinical characteristics of interest (PANSS scores, PAS infancy and premorbid IQ) in the FEP sample. RESULTS COMT influenced the diagnostic differences mainly in PFC-VOL, but also in EF performance. FEP-Val carriers showed lower EF scores and reduced PFC-VOL compared to the HC group but also poorer EF performance than FEP Met/Met. Poorer EF performance was associated with smaller PFC-VOL, and both were related to increased severity of negative symptoms, poorer premorbid adjustment, and lower estimated premorbid IQ in FEP patients. CONCLUSIONS Our findings suggest that COMT Val158Met polymorphism might contribute to PFC-VOL reductions, executive dysfunctions and symptom severity in FEP patients.
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Affiliation(s)
- Elisa Rodríguez-Toscano
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Experimental Psychology, Cognitive Psychology and Speech & Language Therapy Immunology, Faculty of Psychology, Universidad Complutense Madrid, Spain.
| | - Kenia Martínez
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber del Area de Salud Mental (CIBERSAM), Spain
| | - David Fraguas
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber del Area de Salud Mental (CIBERSAM), Spain; School of Medicine, Universidad Complutense, Madrid, Spain
| | - Joost Janssen
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber del Area de Salud Mental (CIBERSAM), Spain
| | - Laura Pina-Camacho
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber del Area de Salud Mental (CIBERSAM), Spain; Department of Child and Adolescent Psychiatry, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK
| | - Bárbara Arias
- Departament Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, CIBERSAM, Barcelona, Spain
| | - Eduard Vieta
- Ciber del Area de Salud Mental (CIBERSAM), Spain; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
| | - Gisela Mezquida
- Ciber del Area de Salud Mental (CIBERSAM), Spain; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clinic of Barcelona, Neuroscience Institute, Spain; Department of Medicine, Institut de Neurociències, Universitat de Barcelona, Spain
| | - Silvia Amoretti
- Ciber del Area de Salud Mental (CIBERSAM), Spain; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clinic of Barcelona, Neuroscience Institute, Spain; Department of Medicine, Institut de Neurociències, Universitat de Barcelona, Spain
| | - Miguel Bernardo
- Ciber del Area de Salud Mental (CIBERSAM), Spain; Hospital Clinic, Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clinic of Barcelona, Neuroscience Institute, Spain; Department of Medicine, Institut de Neurociències, Universitat de Barcelona, Spain; August Pi I Sunyer Biomedical Research Institute (IDIBAPS), Spain
| | - Josefina Castro-Fornieles
- Department of Child and Adolescent Psychiatry and Psychology, Clínic Institute of Neurosciences, Hospital Clínic de Barcelona, 2017SGR881, University of Barcelona, CIBERSAM, IDIBAPS, Barcelona, Spain
| | - Manuel Jesús Cuesta-Zorita
- Department of Psychiatry, Complejo Hospitalario de Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Antonio Lobo
- Department of Medicine and Psychiatry, Zaragoza University, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, CIBERSAM, Madrid, Spain
| | - Ana González-Pinto
- Ciber del Area de Salud Mental (CIBERSAM), Spain; Department of Psychiatry, Araba University Hospital, Bioaraba Research Institute, Department of Neurociences, University of the Basque Country, Vitoria, Spain
| | - Iluminada Corripio Collado
- Department of Psychiatry, Sant Pau Hospital, Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain
| | - Anna Mané
- Ciber del Area de Salud Mental (CIBERSAM), Spain; Hospital del Mar Medical Research Institute (IMIM), Spain; Autonomous University of Barcelona, Spain
| | - Celso Arango
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber del Area de Salud Mental (CIBERSAM), Spain; School of Medicine, Universidad Complutense, Madrid, Spain
| | - Mara Parellada
- Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; Ciber del Area de Salud Mental (CIBERSAM), Spain; School of Medicine, Universidad Complutense, Madrid, Spain
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25
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Chai WJ, Abd Hamid AI, Omar H, Abdul Rahman MR, Fitzrol DN, Idris Z, Ghani ARI, Wan Mohamad WNA, Mustafar F, Hanafi MH, Kandasamy R, Abdullah MZ, Amaruchkul K, Valdes-Sosa PA, Bringas-Vega ML, Biswal B, Songsiri J, Yaacob H, Ibrahim H, Sumari P, Noh NA, Musa KI, Ahmad AH, Azman A, Jamir Singh PS, Othman A, Abdullah JM. Neural alterations in working memory of mild-moderate TBI: An fMRI study in Malaysia. J Neurosci Res 2022; 100:915-932. [PMID: 35194817 DOI: 10.1002/jnr.25023] [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: 12/01/2020] [Revised: 10/10/2021] [Accepted: 12/31/2021] [Indexed: 02/05/2023]
Abstract
Working memory (WM) encompasses crucial cognitive processes or abilities to retain and manipulate temporary information for immediate execution of complex cognitive tasks in daily functioning such as reasoning and decision-making. The WM of individuals sustaining traumatic brain injury (TBI) was commonly compromised, especially in the domain of WM. The current study investigated the brain responses of WM in a group of participants with mild-moderate TBI compared to their healthy counterparts employing functional magnetic resonance imaging. All consented participants (healthy: n = 26 and TBI: n = 15) performed two variations of the n-back WM task with four load conditions (0-, 1-, 2-, and 3-back). The respective within-group effects showed a right hemisphere-dominance activation and slower reaction in performance for the TBI group. Random-effects analysis revealed activation difference between the two groups in the right occipital lobe in the guided n-back with cues, and in the bilateral occipital lobe, superior parietal region, and cingulate cortices in the n-back without cues. The left middle frontal gyrus was implicated in the load-dependent processing of WM in both groups. Further group analysis identified that the notable activation changes in the frontal gyri and anterior cingulate cortex are according to low and high loads. Though relatively smaller in scale, this study was eminent as it clarified the neural alterations in WM in the mild-moderate TBI group compared to healthy controls. It confirmed the robustness of the phenomenon in TBI with the reproducibility of the results in a heterogeneous non-Western sample.
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Affiliation(s)
- Wen Jia Chai
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Aini Ismafairus Abd Hamid
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Hazim Omar
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Muhammad Riddha Abdul Rahman
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- School of Medical Imaging, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Nerus, Malaysia
| | - Diana Noma Fitzrol
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Zamzuri Idris
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Abdul Rahman Izaini Ghani
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Wan Nor Azlen Wan Mohamad
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Faiz Mustafar
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Muhammad Hafiz Hanafi
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | | | - Mohd Zaid Abdullah
- School of Electrical and Electronic Engineering, Universiti Sains Malaysia, Nibong Tebal, Malaysia
| | - Kannapha Amaruchkul
- Graduate School of Applied Statistics, National Institute of Development Administration (NIDA), Bangkok, Thailand
| | - Pedro A Valdes-Sosa
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
- The Cuban Neurosciences Center, La Habana, Cuba
| | - Maria L Bringas-Vega
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
- The Cuban Neurosciences Center, La Habana, Cuba
| | - Bharat Biswal
- Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, USA
| | - Jitkomut Songsiri
- EE410 Control Systems Laboratory, Department of Electrical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, Thailand
| | - Hamwira Yaacob
- Department of Computer Science, Kulliyyah of Information and Communication Technology, Kuala Lumpur, International Islamic University Malaysia, Kuala Lumpur, Malaysia
| | - Haidi Ibrahim
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- School of Electrical and Electronic Engineering, Universiti Sains Malaysia, Nibong Tebal, Malaysia
| | - Putra Sumari
- School of Computer Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | - Nor Azila Noh
- Department of Medical Science 1, Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Nilai, Malaysia
| | - Kamarul Imran Musa
- Department of Community Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Asma Hayati Ahmad
- Department of Physiology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Azlinda Azman
- School of Medical Imaging, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Nerus, Malaysia
- School of Social Sciences, Universiti Sains Malaysia, Pulau Pinang, Malaysia
| | | | - Azizah Othman
- Department of Psychiatry, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Jafri Malin Abdullah
- Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Brain and Behaviour Cluster, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kota Bharu, Malaysia
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26
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Fu X, Quan W, Liu L, Li T, Dong W, Wang J, Tian J, Yan J, Liao J. Similarities and Differences in Brain Activation Between Patients With Schizophrenia and Obsessive-Compulsive Disorder: A Near-Infrared Spectroscopy Study. Front Psychiatry 2022; 13:853428. [PMID: 35558422 PMCID: PMC9086627 DOI: 10.3389/fpsyt.2022.853428] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 03/14/2022] [Indexed: 11/13/2022] Open
Abstract
Schizophrenia (SZ) and obsessive-compulsive disorder (OCD) share several epidemiological and clinical features, but the neurobiological substrates shared by these two diseases remain unclear. This study aimed to explore the similarities and differences in brain function between them using near-infrared spectroscopy (NIRS). Eventually, 130 SZ patients, 70 OCD and 75 normal controls (NCs) were enrolled. A 52-channel NIRS instrument was used to detect the concentration changes in oxygenated hemoglobin ([oxy-Hb]) during the verbal fluency task. Ten regions of interests (ROIs) were defined: the bilateral dorsolateral prefrontal cortex (DLPFC), frontopolar cortex (FPC), orbitofrontal cortex (OFC), inferior prefrontal gyrus (IFG) and temporal gyrus (TG). Through two different analysis strategies based on channels or ROIs, we compared the [oxy-Hb] changes in three groups by one-way analysis of variance (ANOVA) and post-hoc tests. Across 52 channels, compared to the NC group, both SZ and OCD groups exhibited reduced activity in 17 channels, including left FPC, left DLPFC, bilateral OFC, IFG, middle TG, supplementary motor cortex and Broca's area, while SZ showed lower activity in channel 35 (right OFC) than OCD patients. Across all ROIs, compared to the NC group, both SZ and OCD groups showed reduced activity in 7 ROIs, including left FPC, bilateral OFC, IFG and TG, while SZ showed lower activity in the right OFC than OCD group, which were almost consistent with the results based on channels. This study suggests SZ and OCD present with some similar neuropathological changes, while SZ shows more severe impairment in the right OFC than OCD.
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Affiliation(s)
- Xiaoyu Fu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.,Zhongshan Hospital, Fudan University, Xiamen, China
| | - Wenxiang Quan
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Lijun Liu
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Tian Li
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Wentian Dong
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Jiuju Wang
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Ju Tian
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Jun Yan
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
| | - Jinmin Liao
- Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China
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27
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Haghighatfard A, Yaghoubi asl E, Bahadori RA, Aliabadian R, Farhadi M, Mohammadpour F, Tabrizi Z. FOXP2 down expression is associated with executive dysfunctions and electrophysiological abnormalities of brain in Autism spectrum disorder; a neuroimaging genetic study. AUTISM & DEVELOPMENTAL LANGUAGE IMPAIRMENTS 2022; 7:23969415221126391. [PMID: 36382065 PMCID: PMC9620679 DOI: 10.1177/23969415221126391] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
BACKGROUND AND AIMS Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language impairment, and challenges with social interaction, communication, and repetitive behaviors. Although genetics are a primary cause of ASD, the exact genes and molecular mechanisms involved in its pathogenesis are not completely clear. The FOXP2 gene encodes a transcription factor that is known for its major role in language development and severe speech problems. The present study aimed to evaluate the role of FOXP2 in ASD etiology, executive functions, and brain activities. METHODS In the present study, we recruited 450 children with ASD and 490 neurotypical control children. Three domains of executive functions (working memory, response inhibition, and vigilance) were assessed. In addition, five-minute eyes closed electroencephalography was obtained from some of the children with ASD and neurotypical children. DNA sequence and expression level of FOXP2 in blood samples of children with ASD and the control group were evaluated by using sequencing and Real-time PCR, respectively. RESULTS The results showed no mutations but a significant down expression of FOXP2 genes in children with ASD vs. neurotypical children. Several cognitive and executive function deficiencies were detected in children with ASD. Low alpha and gamma bands in the frontal lobe and high theta bands in the occipital lobe were revealed in children with ASD. We also found several correlations between FOXP2 expression levels and clinical assessments. CONCLUSIONS Our finding revealed the down expression of FOXP2, which could be considered as a biomarker for ASD as well as cognitive and executive dysfunction. Based on brain mapping data, FOXP2 may be related to the theta wave abnormality of children with ASD. FOXP2 may be considered a target of novel treatment to improve memory and executive functions. IMPLICATIONS Our findings highlight the role of FOXP2 mRNA level in ASD etiology, executive functions, and brain wave frequencies.
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Affiliation(s)
- Arvin Haghighatfard
- Arvin Haghighatfard, Department of Biology,
North Tehran Branch, Islamic Azad University, Tehran, Iran.
| | - Elham Yaghoubi asl
- Department of neuroscience, Iran University of medical
sciences, Tehran, Iran
| | | | - Rojina Aliabadian
- Department of Genetics, Faculty of Advanced
Science and Technology, Tehran Medical Sciences, Islamic Azad
University, Tehran, Iran
| | - Mahdi Farhadi
- Department of biology, science and research
Branch, Islamic Azad
University, Tehran, Iran
| | - Fatemeh Mohammadpour
- Neuroimaging genetic laboratory, Arvin Gene
Company, Tehran, Iran
- Department of biology, university of
Guilan, Rasht, Iran
| | - Zeinab Tabrizi
- Neuroimaging genetic laboratory, Arvin Gene
Company, Tehran, Iran
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28
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Romero S, de la Serna E, Baeza I, Valli I, Pariente JC, Picado M, Bargalló N, Sugranyes G, Castro-Fornieles J. Altered White Matter Integrity at Illness Onset in Adolescents With a First Episode of Psychosis. Front Psychiatry 2022; 13:876793. [PMID: 35619614 PMCID: PMC9127302 DOI: 10.3389/fpsyt.2022.876793] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/22/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Disruption in white matter integrity has been consistently observed in individuals with psychosis. However, whether such abnormalities are already present at illness onset or are related to downstream processes remains elusive. The study of adolescents with a recent onset of psychosis provides the opportunity to evaluate white matter integrity proximally to disease onset. METHODS Twenty-six adolescents (aged 15.9 ± 1.3 years) with a first episode of psychosis (FEP) (less than 6 months duration) were compared with 26 age and sex-matched healthy controls (HC) (16.8 ± 2 years). In participants with a FEP, clinical diagnoses were confirmed after a minimum of 1 year follow-up (main categories: schizophrenia, bipolar disorder, or schizoaffective disorder). Anatomical images and diffusion tensor sequences were acquired using a 1.5T scanner. Whole brain, voxel-wise group differences in fractional anisotropy (FA) were investigated between participants with a FEP and controls. RESULTS Relative to HC, FEP participants displayed decreased FA in the right posterior cingulate gyrus, encompassing the right superior and posterior corona radiata, and the right parahippocampal gyrus, including the cingulum and fornix. FEP patients showed no areas of increased FA relative to HC. The results remained significant after controlling for medication, cannabis use and intelligence. CONCLUSION Our findings indicate that adolescents with recent onset of psychotic disorders show decreased white matter integrity in circuits implicated in cognitive functions and emotion regulation.
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Affiliation(s)
- Soledad Romero
- Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Elena de la Serna
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Inmaculada Baeza
- Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Isabel Valli
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - José Carlos Pariente
- Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Marisol Picado
- Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Barcelona, Spain
| | - Nuria Bargalló
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Image Diagnostic Center, Hospital Clinic of Barcelona, Barcelona, Spain
| | - Gisela Sugranyes
- Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Josefina Castro-Fornieles
- Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic Barcelona, Barcelona, Spain.,Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.,Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.,Department of Medicine, University of Barcelona, Barcelona, Spain
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29
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Aryutova K, Paunova R, Kandilarova S, Stoyanova K, Maes MHJ, Stoyanov D. Differential aberrant connectivity of precuneus and anterior insula may underpin the diagnosis of schizophrenia and mood disorders. World J Psychiatry 2021; 11:1274-1287. [PMID: 35070777 PMCID: PMC8717032 DOI: 10.5498/wjp.v11.i12.1274] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 06/15/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Over the past decade, resting-state functional magnetic resonance imaging (rs-fMRI) has concentrated on brain networks such as the default mode network (DMN), the salience network (SN), and the central executive network (CEN), allowing for a better understanding of cognitive deficits observed in mental disorders, as well as other characteristic psychopathological phenomena such as thought and behavior disorganization. AIM To investigate differential patterns of effective connectivity across distributed brain networks involved in schizophrenia (SCH) and mood disorders. METHODS The sample comprised 58 patients with either paranoid syndrome in the context of SCH (n = 26) or depressive syndrome (Ds) (n = 32), in the context of major depressive disorder or bipolar disorder. The methods used include rs-fMRI and subsequent dynamic causal modeling to determine the direction and strength of connections to and from various nodes in the DMN, SN and CEN. RESULTS A significant excitatory connection from the dorsal anterior cingulate cortex to the anterior insula (aI) was observed in the SCH patient group, whereas inhibitory connections from the precuneus to the ventrolateral prefrontal cortex and from the aI to the precuneus were observed in the Ds group. CONCLUSION The results delineate specific patterns associated with SCH and Ds and offer a better explanation of the underlying mechanisms of these disorders, and inform differential diagnosis and precise treatment targeting.
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Affiliation(s)
- Katrin Aryutova
- Psychiatry and Medical Psychology, Medical University, Plovdiv 4002, Bulgaria
| | - Rositsa Paunova
- Research Institute, Medical University, Plovdiv 4002, Bulgaria
| | | | | | - Michael HJ Maes
- Research Institute, Medical University, Plovdiv 4002, Bulgaria
| | - Drozdstoy Stoyanov
- Psychiatry and Medical Psychology, Medical University, Plovdiv 4002, Bulgaria
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30
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The central executive network and executive function in healthy and persons with schizophrenia groups: a meta-analysis of structural and functional MRI. Brain Imaging Behav 2021; 16:1451-1464. [PMID: 34775552 DOI: 10.1007/s11682-021-00589-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2021] [Indexed: 10/19/2022]
Abstract
This meta-analysis evaluated the extent to which executive function can be understood with structural and functional magnetic resonance imaging. Studies included structural in schizophrenia (k = 8; n = 241) and healthy controls (k = 12; n = 1660), and functional in schizophrenia (k = 4; n = 104) and healthy controls (k = 12; n = 712). Results revealed a positive association in the brain behavior relationship when pooled across schizophrenia and control samples for structural (pr = 0.27) and functional (pr = 0.29) modalities. Subgroup analyses revealed no significant difference for functional neuroimaging (pr = .43, 95%CI = -.08-.77, p = .088) but with structural neuroimaging (pr = .37, 95%CI = -.08-.69, p = .015) the association to executive functions is lower in the control group. Subgroup analyses also revealed no significant differences in the strength of the brain-behavior relationship in the schizophrenia group (pr = .59, 95%CI = .58-.61, p = .881) or the control group (pr = 0.19, 95%CI = 0.18-0.19, p = 0.920), suggesting concordance.
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31
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Rodríguez-Toscano E, Martínez K, Fraguas D, Janssen J, Pina-Camacho L, Arias B, Vieta E, Mezquida G, Amoretti S, Bernardo M, Castro-Fornieles J, Cuesta-Zorita MJ, Lobo A, González-Pinto A, Collado IC, Mané A, Arango C, Parellada M. Prefrontal abnormalities, executive dysfunction and symptoms severity are modulated by COMT Val158Met polymorphism in first episode psychosis. REVISTA DE PSIQUIATRIA Y SALUD MENTAL 2021. [PMID: 35840287 DOI: 10.1016/j.rpsm.2021.11.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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32
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Speers LJ, Bilkey DK. Disorganization of Oscillatory Activity in Animal Models of Schizophrenia. Front Neural Circuits 2021; 15:741767. [PMID: 34675780 PMCID: PMC8523827 DOI: 10.3389/fncir.2021.741767] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/16/2021] [Indexed: 01/02/2023] Open
Abstract
Schizophrenia is a chronic, debilitating disorder with diverse symptomatology, including disorganized cognition and behavior. Despite considerable research effort, we have only a limited understanding of the underlying brain dysfunction. In this article, we review the potential role of oscillatory circuits in the disorder with a particular focus on the hippocampus, a region that encodes sequential information across time and space, as well as the frontal cortex. Several mechanistic explanations of schizophrenia propose that a loss of oscillatory synchrony between and within these brain regions may underlie some of the symptoms of the disorder. We describe how these oscillations are affected in several animal models of schizophrenia, including models of genetic risk, maternal immune activation (MIA) models, and models of NMDA receptor hypofunction. We then critically discuss the evidence for disorganized oscillatory activity in these models, with a focus on gamma, sharp wave ripple, and theta activity, including the role of cross-frequency coupling as a synchronizing mechanism. Finally, we focus on phase precession, which is an oscillatory phenomenon whereby individual hippocampal place cells systematically advance their firing phase against the background theta oscillation. Phase precession is important because it allows sequential experience to be compressed into a single 120 ms theta cycle (known as a 'theta sequence'). This time window is appropriate for the induction of synaptic plasticity. We describe how disruption of phase precession could disorganize sequential processing, and thereby disrupt the ordered storage of information. A similar dysfunction in schizophrenia may contribute to cognitive symptoms, including deficits in episodic memory, working memory, and future planning.
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Affiliation(s)
| | - David K. Bilkey
- Department of Psychology, Otago University, Dunedin, New Zealand
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33
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Dahlén A, Zarei M, Melgoza A, Wagle M, Guo S. THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior. Sci Rep 2021; 11:15693. [PMID: 34344922 PMCID: PMC8333334 DOI: 10.1038/s41598-021-95016-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/14/2021] [Indexed: 11/09/2022] Open
Abstract
High doses of the Cannabis constituent Δ9-tetrahydrocannabinol (THC) increase the risk of psychosis in humans. Highly accessible animal models are needed to address underlying mechanisms. Using zebrafish with a conserved endocannabinoid system, this study investigates the acute effects of THC on adult zebrafish behavior and the mechanisms involved. A concentration-dependent THC-induced behavioral stereotypy akin to THC's effect in rats and the psychotropics phencyclidine and ketamine in zebrafish was established. Distinctive circular swimming during THC-exposure was measured using a novel analytical method that we developed, which detected an elevated Repetition Index (RI) compared to vehicle controls. This was reduced upon co-administration of N-methyl-D-aspartate (NMDA) receptor agonist NMDA, suggesting that THC exerts its effects via biochemical or neurobiological mechanisms associated with NMDA receptor antagonism. Co-treatment of γ-aminobutyric acid receptor antagonist pentylenetetrazol also showed signs of reducing the RI. Since THC-induced repetitive behavior remained in co-administrations with cannabinoid receptor 1 inverse agonist AM251, the phenotype may be cannabinoid receptor 1-independent. Conversely, the inverse cannabinoid receptor 2 agonist AM630 significantly reduced THC-induced behavioral stereotypy, indicating cannabinoid receptor 2 as a possible mediator. A significant reduction of the THC-RI was also observed by the antipsychotic sulpiride. Together, these findings highlight this model's potential for elucidating the mechanistic relationship between Cannabis and psychosis.
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Affiliation(s)
- Amelia Dahlén
- Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA.
- Section of Functional Pharmacology, Department of Neuroscience, Uppsala University, 75124, Uppsala, Sweden.
| | - Mahdi Zarei
- Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA
| | - Adam Melgoza
- Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA
| | - Mahendra Wagle
- Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA
| | - Su Guo
- Department of Bioengineering and Therapeutic Sciences, and Programs in Biological Sciences and Human Genetics, University of California, San Francisco, CA, 94158, USA.
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Aydın O, Balıkçı K, Sönmez İ, Ünal-Aydın P, Spada MM. Examining the roles of cognitive flexibility, emotion recognition, and metacognitions in adult Attention Deficit and Hyperactivity Disorder with predominantly inattentive presentation. Clin Psychol Psychother 2021; 29:542-553. [PMID: 34272785 DOI: 10.1002/cpp.2645] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 05/28/2021] [Accepted: 06/28/2021] [Indexed: 11/10/2022]
Abstract
The evaluation of cognitive functions in Attention Deficit and Hyperactivity Disorder (ADHD) is fundamental to improve the efficacy of therapeutic interventions. However, the role of specific higher-order cognitive functions in adult ADHD, including cognitive flexibility, emotion recognition, and metacognitions, remains unclear. Therefore, in the current study, we aimed to examine these three distinct higher-order cognitive functions among adult ADHD individuals. Forty patients with ADHD with predominantly inattentive presentation and 42 healthy controls participated in the study. The Adult Attention Deficit and Hyperactivity Disorder Scale (AADHDS), the Wisconsin Card Sorting Test (WCST), the Reading the Mind in the Eyes Test (RMET), and the Metacognitions Questionnaire-30 (MCQ-30) were administered. Results indicated that patients with ADHD had worse metacognitions scores, in specific subdimensions, relative to healthy controls. However, cognitive flexibility and emotion recognition did not differ between the groups. Moreover, the cognitive confidence subdimension of the MCQ-30 was found to be sole significant predictor in the attention deficit subdimension of the AADHDS. Our findings suggest that lack of cognitive confidence may contribute to ADHD symptomatology despite regularly functioning cognitive flexibility and emotion recognition. Therefore, metacognitions could be a suitable target to alleviate the severity of ADHD symptoms.
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Affiliation(s)
- Orkun Aydın
- Department of Psychology, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Kuzeymen Balıkçı
- Department of Psychology, Cyprus Social Sciences University, Nicosia, Cyprus
| | - İpek Sönmez
- Department of Psychiatry, Near East University Faculty of Medicine, Nicosia, Cyprus
| | - Pınar Ünal-Aydın
- Department of Psychology, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Marcantonio M Spada
- Division of Psychology, School of Applied Sciences, London South Bank University, London, UK
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Tyburski E, Mak M, Sokołowski A, Starkowska A, Karabanowicz E, Kerestey M, Lebiecka Z, Preś J, Sagan L, Samochowiec J, Jansari AS. Executive Dysfunctions in Schizophrenia: A Critical Review of Traditional, Ecological, and Virtual Reality Assessments. J Clin Med 2021; 10:jcm10132782. [PMID: 34202881 PMCID: PMC8267962 DOI: 10.3390/jcm10132782] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/11/2021] [Accepted: 06/18/2021] [Indexed: 01/19/2023] Open
Abstract
In recent years, interest has grown in measuring executive function in schizophrenia with ecological and virtual reality (VR) tools. However, there is a lack of critical analysis comparing those tools with traditional ones. This paper aims to characterize executive dysfunction in schizophrenia by comparing ecological and virtual reality assessments with traditional tools, and to describe the neurobiological and psychopathological correlates. The analysis revealed that ecological and VR tests have higher levels of verisimilitude and similar levels of veridicality compared to traditional tools. Both negative symptoms and disorganization correlate significantly with executive dysfunction as measured by traditional tools, but their relationships with measures based on ecological and VR methods are still unclear. Although there is much research on brain correlates of executive impairments in schizophrenia with traditional tools, it is uncertain if these results will be confirmed with the use of ecological and VR tools. In the diagnosis of executive dysfunction, it is important to use a variety of neuropsychological methods—especially those with confirmed ecological validity—to properly recognize the underlying characteristics of the observed deficits and to implement effective forms of therapy.
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Affiliation(s)
- Ernest Tyburski
- Institute of Psychology, SWPS University of Social Sciences and Humanities, 61-719 Poznań, Poland
- Correspondence: ; Tel.: +48-61-271-12-22
| | - Monika Mak
- Department of Health Psychology, Pomeranian Medical University in Szczecin, 71-457 Szczecin, Poland; (M.M.); (Z.L.); (J.P.)
| | - Andrzej Sokołowski
- Memory and Aging Center, Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, 675 Nelson Rising Lane, Suite 190, San Francisco, CA 94143, USA;
| | - Anna Starkowska
- Faculty of Psychology in Wrocław, SWPS University of Social Sciences and Humanities, 53-238 Wrocław, Poland;
| | - Ewa Karabanowicz
- Institute of Psychology, University of Szczecin, 71-017 Szczecin, Poland; (E.K.); (M.K.)
| | - Magdalena Kerestey
- Institute of Psychology, University of Szczecin, 71-017 Szczecin, Poland; (E.K.); (M.K.)
| | - Zofia Lebiecka
- Department of Health Psychology, Pomeranian Medical University in Szczecin, 71-457 Szczecin, Poland; (M.M.); (Z.L.); (J.P.)
| | - Joanna Preś
- Department of Health Psychology, Pomeranian Medical University in Szczecin, 71-457 Szczecin, Poland; (M.M.); (Z.L.); (J.P.)
| | - Leszek Sagan
- Department of Neurosurgery, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland;
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University in Szczecin, 71-457 Szczecin, Poland;
| | - Ashok S. Jansari
- Department of Psychology, Goldsmiths, University of London, New Cross, London SE14 6NW, UK;
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Chamera K, Szuster-Głuszczak M, Basta-Kaim A. Shedding light on the role of CX3CR1 in the pathogenesis of schizophrenia. Pharmacol Rep 2021; 73:1063-1078. [PMID: 34021899 PMCID: PMC8413165 DOI: 10.1007/s43440-021-00269-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/22/2021] [Accepted: 04/26/2021] [Indexed: 11/24/2022]
Abstract
Schizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1–CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1–CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1–CX3CR1 dysfunctions in the course of schizophrenia.
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Affiliation(s)
- Katarzyna Chamera
- Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343, Kraków, Poland.
| | - Magdalena Szuster-Głuszczak
- Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343, Kraków, Poland
| | - Agnieszka Basta-Kaim
- Laboratory of Immunoendocrinology, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St., 31-343, Kraków, Poland
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37
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Foraita M, Howell T, Bennett P. Environmental influences on development of executive functions in dogs. Anim Cogn 2021; 24:655-675. [PMID: 33611642 DOI: 10.1007/s10071-021-01489-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/21/2021] [Accepted: 02/06/2021] [Indexed: 12/14/2022]
Abstract
Executive functions (EFs) are a set of cognitive processes used for effortful self-regulation of behaviour. They include inhibition, working memory, cognitive flexibility and, in some models, attention. In humans, socioeconomic factors and life experiences shape development of EFs. Domestic dogs (Canis familiaris) must often regulate their behaviour in the human environment (e.g. no jumping up on humans or chasing cats), and life experiences also probably influence the development of EFs in dogs. Research into dog cognition and behaviour has been thriving, and some methods used to explore these concepts (e.g. object-choice task, questionnaires measuring traits like distraction and aggression) are likely to be sensitive to differences in EFs, even if that is not their stated aim. Here we examine relevant studies to identify experiential factors which may influence the development of EFs in dogs living in human care. These are early experience, training, housing and stress. We conclude that the development of dogs' EFs may be negatively affected by hardships, and positively by surmountable challenges, early in life. Training methods appear important, with punishment-based methods leading to poorer dog EFs. Kennel environments seem to affect dog EFs negatively. While mild stressors might enhance the development of EFs, too much stress seems to have negative effects. Regulation of behaviour, a key outcome of EFs, is crucial for dogs' integration into human society. We should, therefore, strive to better understand how the environment shapes dogs' EFs.
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Affiliation(s)
- Maike Foraita
- Anthrozoology Research Group, School of Psychology and Public Health, La Trobe University, Melbourne, Australia.
| | - Tiffani Howell
- Anthrozoology Research Group, School of Psychology and Public Health, La Trobe University, Melbourne, Australia
| | - Pauleen Bennett
- Anthrozoology Research Group, School of Psychology and Public Health, La Trobe University, Melbourne, Australia
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Egger ST, Bobes J, Rauen K, Seifritz E, Vetter S, Schuepbach D. Psychopathological Symptom Load and Distinguishable Cerebral Blood Flow Velocity Patterns in Patients With Schizophrenia and Healthy Controls: A Functional Transcranial Doppler Study. Front Psychiatry 2021; 12:679021. [PMID: 34248715 PMCID: PMC8267584 DOI: 10.3389/fpsyt.2021.679021] [Citation(s) in RCA: 7] [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: 03/10/2021] [Accepted: 05/21/2021] [Indexed: 01/03/2023] Open
Abstract
Introduction: Schizophrenia is a severe psychiatric disorder, with executive dysfunction and impaired processing speed playing a pivotal role in the course of the disease. In patients with schizophrenia, neurocognitive deficits appear to be related to alterations in cerebral hemodynamics. It is not fully understood if psychopathological symptom load (i.e., presence and severity of symptoms) is also related to alterations in cerebral hemodynamics. We aim to study the relationship between psychopathological symptom load and cerebral hemodynamics in the Middle Cerebral Artery (MCA) during a cognitive task in patients with schizophrenia and healthy controls. Methodology: Cerebral hemodynamics in the MCA were examined in 30 patients with schizophrenia and 15 healthy controls using functional Transcranial Doppler (fTCD) during the Trail Making Test (TMT). Psychopathological symptoms were measured using the Brief Psychiatric Rating Scale (BPRS). Patients were dichotomized according to BPRS scores: mild-moderate (BPRS < 41, n = 15) or marked-severe (BPRS ≧ 41, n = 15). Mean blood flow velocity (MFV) in the MCA and processing speed of the TMT were analyzed. Cerebral hemodynamics were analyzed using the general additional model (GAM) with a covariate analysis of variance (ANCOVA) for group comparisons. Results: Patients and healthy controls were comparable regarding demographics. Patients had a slower processing speed for the TMT-A (patients-severe: 52s, patients-moderate: 40s, healthy-controls: 32s, p = 0.019) and TMT-B [patients-severe: 111s, patients-moderate: 76s, healthy-controls: 66s, p < 0.001)]. Patients demonstrated differing hemodynamic profiles in both TMTs: TMT- A [F (6, 1,792) = 17, p < 0.000); TMT-B [F (6, 2,692) = 61.93, p < 0.000], with a delay in increase in MFV and a failure to return to baseline values. Conclusions: Patients with schizophrenia demonstrated slower speeds of processing during both the TMT-A and TMT-B. The speed of processing deteriorated with increasing psychopathological symptom load, additionally a distinct cerebral hemodynamic pattern in the MCA was observed. Our results further support the view that severity of schizophrenia, particularly psychopathological symptom load, influences performance in neurocognitive tasks and is related to distinct patterns of brain hemodynamics.
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Affiliation(s)
- Stephan T Egger
- Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, University Hospital of Zurich, University of Zürich, Zurich, Switzerland.,Department of Psychiatry, Faculty of Medicine, University of Oviedo, Oviedo, Spain
| | - Julio Bobes
- Department of Psychiatry, Faculty of Medicine, University of Oviedo, Oviedo, Spain
| | - Katrin Rauen
- Department of Geriatric Psychiatry, Faculty of Medicine, Psychiatric University Hospital of Zurich, University of Zürich, Zurich, Switzerland.,Institute for Stroke and Dementia Research, Ludwig Maximilian University Munich, University Hospital, Munich, Germany
| | - Erich Seifritz
- Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, University Hospital of Zurich, University of Zürich, Zurich, Switzerland
| | - Stefan Vetter
- Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, University Hospital of Zurich, University of Zürich, Zurich, Switzerland
| | - Daniel Schuepbach
- Department of General Psychiatry, Center of Psychosocial Medicine, University of Heidelberg, Heidelberg, Germany.,Klinikum am Weissenhof, Weinsberg, Germany
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Aydın O, Obuća F, Boz C, Ünal-Aydın P. Associations between executive functions and problematic social networking sites use. J Clin Exp Neuropsychol 2020; 42:634-645. [DOI: 10.1080/13803395.2020.1798358] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Orkun Aydın
- Department of Psychology, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Faruk Obuća
- Department of Psychology, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Canahmet Boz
- Department of Psychology, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Pınar Ünal-Aydın
- Department of Psychology, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina
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40
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Executive dysfunctions differentially predict amotivation in first-episode schizophrenia-spectrum disorder: a prospective 1-year follow-up study. Eur Arch Psychiatry Clin Neurosci 2019; 269:887-896. [PMID: 29934845 DOI: 10.1007/s00406-018-0918-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 06/18/2018] [Indexed: 10/28/2022]
Abstract
Amotivation is a major determinant of functional outcome in schizophrenia but it is understudied in the early course of illness. There is a paucity of longitudinal research investigating predictors of amotivation. In this study, we aimed to examine baseline cognitive and clinical predictors of amotivation at 6 and 12 months of follow-up in patients aged 18-55 years presenting with first-episode DSM-IV schizophrenia-spectrum disorder (FES). Of 145 patients recruited at intake, 116 and 113 completed assessments at 6- and 12-month follow-up, respectively. Amotivation was measured by avolition-apathy and anhedonia-asociality subscale scores of the Scale of the Assessment of Negative Symptoms. Cognitive assessment was administered at baseline. As executive dysfunction has been more consistently found to be associated with negative symptoms and amotivation in prior literature, we adopted fractionated approach to subdivide executive function into distinct components encompassing switching and flexibility, response initiation, response inhibition, planning and strategy allocation, sustained attention and working memory. Our results showed that baseline amotivation (p = 0.01) and switching and flexibility (p = 0.01) were found to independently predict amotivation at 6 months follow-up. Baseline amotivation (p < 0.01) and switching and flexibility (albeit with trend-wise significance, p = 0.06) were also retained in final multivariate regression model for 12-month amotivation prediction. No other executive components or cognitive domains predicted amotivation at follow-up. Findings of our study thus indicate amotivation at initial presentation as a critical determinant of subsequent motivational deficits over 1 year of treatment for FES patients. Cognitive flexibility might be specifically related to the development of amotivation in the early stage of illness.
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41
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Sardari S, Pourrahimi AM, Talebi H, Mazhari S. Symmetrical electrophysiological brain responses to unilateral and bilateral auditory stimuli suggest disrupted spatial processing in schizophrenia. Sci Rep 2019; 9:16454. [PMID: 31712599 PMCID: PMC6848080 DOI: 10.1038/s41598-019-52931-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Accepted: 10/26/2019] [Indexed: 11/08/2022] Open
Abstract
Research has found auditory spatial processing deficits in patients with schizophrenia (SCZ), but no study has examined SCZ patients' auditory spatial processing at both pre-attentional and attentional stages. To address this gap, we investigated schizophrenics' brain responses to sounds originating from different locations (right, left, and bilateral sources). The event-related potentials (ERPs) of 25 chronic schizophrenic patients and 25 healthy subjects were compared. Mismatch negativity (MMN) in response to frequency and duration deviants was assessed. Two P3 components (P3a and P3b) were elicited via a frequency discrimination task, and MMN and P3 were recorded through separate monaural and dichotic stimulation paradigms. Our results corroborated the previously published finding that MMN, P3a, and P3b amplitudes are reduced in SCZ patients, but they showed no significant effect of stimulus location on either MMN or P3. These results indicated similarity between the SCZ patients and healthy individuals as regards patterns of ERP responses to stimuli that come from different directions. No evidence of auditory hemispatial bias in the SCZ patients was found, supporting the existence of non-lateralized spatial processing deficits in such patients and suggesting compensatory changes in the hemispheric laterality of patients' brains.
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Affiliation(s)
- Sara Sardari
- Neuroscience Research center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Ali Mohammad Pourrahimi
- Neuroscience Research center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Hossein Talebi
- Audiology department, Rehabilitation faculty, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shahrzad Mazhari
- Neuroscience Research center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
- Department of Psychiatry, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
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Kroll J, Karolis V, Brittain PJ, Tseng CEJ, Froudist-Walsh S, Murray RM, Nosarti C. Systematic assessment of perinatal and socio-demographic factors associated with IQ from childhood to adult life following very preterm birth. INTELLIGENCE 2019. [DOI: 10.1016/j.intell.2019.101401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Vanes LD, Mouchlianitis E, Patel K, Barry E, Wong K, Thomas M, Szentgyorgyi T, Joyce D, Shergill S. Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia. Sci Rep 2019; 9:14444. [PMID: 31595009 PMCID: PMC6783468 DOI: 10.1038/s41598-019-51023-0] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 09/23/2019] [Indexed: 12/14/2022] Open
Abstract
Psychotic illness is associated with cognitive control deficits and abnormal recruitment of neural circuits subserving cognitive control. It is unclear to what extent this dysfunction underlies the development and/or maintenance of positive and negative symptoms typically observed in schizophrenia. In this study we compared fMRI activation on a standard Stroop task and its relationship with positive and negative symptoms in early psychosis (EP, N = 88) and chronic schizophrenia (CHR-SZ, N = 38) patients. CHR-SZ patients showed reduced frontal, striatal, and parietal activation across incongruent and congruent trials compared to EP patients. Higher positive symptom severity was associated with reduced activation across both trial types in supplementary motor area (SMA), middle temporal gyrus and cerebellum in EP, but not CHR-SZ patients. Higher negative symptom severity was associated with reduced cerebellar activation in EP, but not in CHR-SZ patients. A negative correlation between negative symptoms and activation in SMA and precentral gyrus was observed in EP patients and in CHR-SZ patients. The results suggest that the neural substrate of positive symptoms changes with illness chronicity, and that cognitive control related neural circuits may be most relevant in the initial development phase of positive symptoms. These findings also highlight a changing role for the cerebellum in the development and later maintenance of both positive and negative symptoms.
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Affiliation(s)
- Lucy D Vanes
- Wellcome Centre for Human Neuroimaging, University College London, 12 Queen Square, London, WC1N 3AR, United Kingdom.
| | - Elias Mouchlianitis
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
| | - Krisna Patel
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
| | - Erica Barry
- Institute Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, USA
| | - Katie Wong
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
| | - Megan Thomas
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
| | - Timea Szentgyorgyi
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
| | - Dan Joyce
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
| | - Sukhwinder Shergill
- Institute of Psychiatry, Psychology and Neuroscience, de Crespigny Park, London, SE5 8AF, United Kingdom
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Avery SN, Armstrong K, Blackford JU, Woodward ND, Cohen N, Heckers S. Impaired relational memory in the early stage of psychosis. Schizophr Res 2019; 212:113-120. [PMID: 31402078 PMCID: PMC6791765 DOI: 10.1016/j.schres.2019.07.060] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Revised: 05/28/2019] [Accepted: 07/30/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Humans constantly take in vast amounts of information, which must be filtered, flexibly manipulated, and integrated into cohesive relational memories in order to choose relevant behaviors. Relational memory is impaired in chronic schizophrenia, which has been linked to hippocampal dysfunction. It is unclear whether relational memory is impaired in the early stage of psychosis. METHODS We studied eye movements during a face-scene pairs task as an indirect measure of relational memory in 89 patients in the early stage of psychosis and 84 healthy control participants. During testing, scenes were overlaid with three equally-familiar faces and participants were asked to recall the matching (i.e. previously-paired) face. During Match trials, one face had been previously paired with the scene. During Non-Match trials, no faces matched the scene. Forced-choice explicit recognition was recorded as a direct measure of relational memory. RESULTS Healthy control subjects rapidly (within 250-500 ms) showed preferential viewing of the matching face during Match trials. In contrast, preferential viewing was delayed in patients in the early stage of psychosis. Explicit recognition of the matching face was also impaired in the patient group. CONCLUSIONS This study provides novel evidence for a relational memory deficit in the early stage of psychosis. Patients showed deficits in both explicit recognition as well as abnormal eye-movement patterns during memory recall. Eye movements provide a promising avenue for the study of relational memory in psychosis, as they allow for the assessment of rapid, nonverbal memory processes.
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Affiliation(s)
- Suzanne N. Avery
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37212 USA
| | - Kristan Armstrong
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37212 USA
| | - Jennifer U. Blackford
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37212 USA,Research Health Scientist, Research and Development, Department of Veterans Affairs Medical Center, Nashville, TN
| | - Neil D. Woodward
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37212 USA
| | - Neal Cohen
- Beckman Institute for Advanced Science and Technology, and Interdisciplinary Health Sciences Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801 USA
| | - Stephan Heckers
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37212 USA
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Bosco FM, Berardinelli L, Parola A. The Ability of Patients With Schizophrenia to Comprehend and Produce Sincere, Deceitful, and Ironic Communicative Intentions: The Role of Theory of Mind and Executive Functions. Front Psychol 2019; 10:827. [PMID: 31139103 PMCID: PMC6519037 DOI: 10.3389/fpsyg.2019.00827] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 03/28/2019] [Indexed: 12/17/2022] Open
Abstract
Patients with schizophrenia are often described as impaired in several cognitive domains. Specifically, patients with schizophrenia often exhibit problems in solving tasks requiring theory of mind (ToM), i.e., the ability to ascribe mental states to oneself and others, communicative-pragmatic ability, i.e., the ability to use language and non-verbal expressive means to convey meaning in a given context, and executive functions (EF). This study aims to investigate the role of cognitive functions, such as general intelligence, selective attention, processing speed, and especially EF (working memory, cognitive flexibility, inhibition, and planning), and ToM in explaining the performance of individual with schizophrenia in comprehending and producing communicative acts expressed with different communicative intentions (i.e., sincere, deceitful, and ironic), and realized through linguistic and extralinguistic/non-verbal expressive means. Thirty-two patients with schizophrenia and an equal number of healthy controls performed tasks aiming to investigate their capacity to comprehend and produce sincere, deceitful, and ironic communicative acts in addition to a series of cognitive tasks evaluating EF and ToM. The results indicated that individuals with schizophrenia performed worse than the controls in the comprehension and production of all pragmatic phenomena investigated, as well as in all the cognitive functions examined. The patients with schizophrenia also exhibited an increasing trend of difficulty in comprehending and producing sincere, deceitful, and ironic communicative acts expressed through either linguistic or extralinguistic means. Furthermore, a multiple regression analysis of the patients' performance on the pragmatic tasks revealed that overall, the role of attention, general intelligence, and processing speed did not appear to significantly explain the patients' communicative-pragmatic performance. The inclusion of EF into the analysis did not contribute to increase the explained variance of the patients' ability to comprehend and produce the various pragmatic phenomena investigated. Only the addition of ToM could significantly increase the explained variance, but only in the comprehension and production of deceit expressed by language and the production of sincere communicative acts, also limited to linguistic production. We conclude that neither EF nor ToM are able to explain the decreasing trend detected in the patients' pragmatic performance.
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Affiliation(s)
- Francesca M. Bosco
- Department of Psychology, University of Turin, Turin, Italy
- Institute of Neuroscience, Turin, Italy
| | | | - Alberto Parola
- Department of Psychology, University of Turin, Turin, Italy
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A dynamic attentional control framework for understanding sleep deprivation effects on cognition. PROGRESS IN BRAIN RESEARCH 2019; 246:111-126. [PMID: 31072558 DOI: 10.1016/bs.pbr.2019.03.015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The cognitive effects of sleep loss are often attributed to compromised functioning of the prefrontal cortex (PFC). However, compromised PFC functioning does not account for well-known effects of sleep deprivation on vigilance. Furthermore, the executive attentional control functions associated with the PFC show considerable variability in the effects of sleep deprivation. Evidence from neuroimaging suggests that sleep deprived people are sometimes able to maintain performance on cognitive tasks by increasing PFC activation of task-relevant circuits and by recruiting new circuits not typically involved in a particular cognitive operation. Still, little is known about how such compensatory processes work on a functional level, or what tradeoffs in processing they may entail. We propose a dynamic attentional control framework to bridge the gap between the evidence on sleep deprived neural circuits and cognitive task performance. We review evidence that shows that the pattern of preserved and compromised task performance can be understood in terms of sleep deprivation's influence on frontostriatal circuitry such that the ability to maintain task-relevant information in the focus of attention is relatively spared but the ability to update task-relevant information in response to changing circumstances is more negatively affected. This framework helps account for why some tasks are more affected by SD than others, and why individual differences in the effects of sleep deprivation are task-specific.
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Rao N, Northoff G, Tagore A, Rusjan P, Kenk M, Wilson A, Houle S, Strafella A, Remington G, Mizrahi R. Impaired Prefrontal Cortical Dopamine Release in Schizophrenia During a Cognitive Task: A [11C]FLB 457 Positron Emission Tomography Study. Schizophr Bull 2019; 45:670-679. [PMID: 29878197 PMCID: PMC6483585 DOI: 10.1093/schbul/sby076] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Evidence from several lines of research suggests decreased dopamine release in the prefrontal cortex as the neurochemical correlates of cognitive deficits in schizophrenia (SCZ). However, in vivo examination of cortical hypodopaminergia using positron emission tomography (PET) during cognitive task performance in SCZ remains to be investigated. We examined dopamine release in anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC), using PET while participants were performing a cognitive task. Thirteen drug-free patients with SCZ and 13 healthy volunteers (HV) matched for age and sex participated in the study. Data were acquired between 2011 and 2015. Two PET scans with [11C]FLB 457 were acquired while the participants were performing the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task (SMCT). A magnetic resonance image was acquired for anatomical delineation. Differences in cortical dopamine release between SCZ and HV, indexed as percentage change in binding potential between WCST and SMCT (ΔBPND), were calculated in ACC and DLPFC. We observed significant differences in the ΔBPND in ACC (HV = 4.40 ± 6.00; SCZ = -11.48 ± 15.08; t = 3.52; P = .003) and a trend-level difference in ΔBPND in DLPFC (HV = -0.58 ± 8.45; SCZ = -7.79 ± 11.28; t = 1.84; P = .079), suggesting dopamine depletion in cortical brain regions in patients with SCZ while performing a cognitive task. These results provide the first in vivo evidence for reduced dopamine release or even dopamine depletion while performing cognitive task in ACC and DLPFC in patients with SCZ. The present results provide support for the frontal hypodopaminergia hypothesis of cognitive symptoms in SCZ.
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Affiliation(s)
- Naren Rao
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada,Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
| | - Georg Northoff
- Institute of Mental Health Research: Mind, Brain Imaging and Neuroethics, University of Ottawa, Ottawa, ON, Canada
| | - Abanti Tagore
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Pablo Rusjan
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Miran Kenk
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Alan Wilson
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Sylvain Houle
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Antonio Strafella
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Gary Remington
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Romina Mizrahi
- Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada,To whom correspondence should be addressed; University of Toronto, Focus on Youth Psychosis Prevention (FYPP), Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8 Canada; tel: 416-535-8501 ext. 34508, fax: 416-979-4656, e-mail:
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Bosia M, Bechi M, Bosinelli F, Politi E, Buonocore M, Spangaro M, Bianchi L, Cocchi F, Guglielmino C, Cavallaro R. From cognitive and clinical substrates to functional profiles: Disentangling heterogeneity in schizophrenia. Psychiatry Res 2019; 271:446-453. [PMID: 30537667 DOI: 10.1016/j.psychres.2018.12.026] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 11/19/2018] [Accepted: 12/05/2018] [Indexed: 01/12/2023]
Abstract
The relationship between neurocognition and functioning among patients with schizophrenia is well documented. However, integrating neuropsychological, clinical and psychopathological data to better investigate functional outcome still constitutes a challenge. Artificial neural network-based modeling might help to better capture clinical heterogeneity by analyzing the non-linear relationships among multiple variables. Two hundred and fourteen clinically stabilized patients with schizophrenia were recruited and assessed for neurocognition, psychopathology and functioning. Artificial neural network analyses were conducted to yield significant predictors of functional outcome among clinical and cognitive variables and to build distinct functional Profiles, each characterized by a different medley of cognitive and clinical features. Twenty-two key predictors of daily functioning emerged, encompassing neurocognitive and clinical domains, with major roles for processing speed and attention. Four Profiles were constructed based on specific levels of functioning, each characterized by a distinct distribution of key clinical and neurocognitve measures. This study highlights the importance of a more in-depth investigation of cognitive and clinical heterogeneity. A better understanding of the building blocks of these Profiles would lead to more individualized rehabilitation treatments.
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Affiliation(s)
- Marta Bosia
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
| | - Margherita Bechi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy.
| | | | - Ernestina Politi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy
| | - Mariachiara Buonocore
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy
| | - Marco Spangaro
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy
| | - Laura Bianchi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy
| | - Federica Cocchi
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy
| | - Carmelo Guglielmino
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy
| | - Roberto Cavallaro
- Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
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Sugawara N, Yasui-Furukori N, Sumiyoshi T. Competence to Consent and Its Relationship With Cognitive Function in Patients With Schizophrenia. Front Psychiatry 2019; 10:195. [PMID: 31031653 PMCID: PMC6474312 DOI: 10.3389/fpsyt.2019.00195] [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: 11/30/2017] [Accepted: 03/18/2019] [Indexed: 12/25/2022] Open
Abstract
Decisional capacity to consent is an emerging ethical and legal concept, and is closely related to self-determination of patients facing important medical decisions or research participations. Recently, the MacArthur Competence Assessment Tool (MacCAT), a semi-structured interview consisting of four dimensions (Understanding, Appreciation, Reasoning, and Expression of a Choice), was developed to assess the decisional capacity. Decision-making capacity in a group of patients with schizophrenia, as measured by the MacCAT, has been shown to be impaired in comparison with healthy control people. However, this does not necessarily mean the presence of impaired decisional capacity in all cases. Considering the real-world practice of obtaining informed consent from patients with schizophrenia, it is important to evaluate the relationship between psychopathological features and decisional capacity of the illness. Negative symptoms of schizophrenia have been demonstrated to be related to the ability to understand information relevant to the decision, reason rationally, and appreciate a situation and its consequences. On the other hand, positive symptoms, such as delusions and hallucinations have been an inconsistent correlate of poor capacity. Furthermore, some studies indicate that impairment of cognitive function, a core symptom of schizophrenia, could be more largely associated with decisional capacity than positive and negative symptoms. Therefore, it is reasonable to assume cognitive enhancement would enlarge the capacity to consent and promote autonomy in medical treatment and research participation in patients with schizophrenia. Further studies are warranted to elucidate this and related issues.
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Affiliation(s)
- Norio Sugawara
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Norio Yasui-Furukori
- Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan
| | - Tomiki Sumiyoshi
- Department of Clinical Epidemiology, Translational Medical Center, National Center of Neurology and Psychiatry, Kodaira, Japan
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50
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Berberian AA, Gadelha A, Dias NM, Mecca TP, Comfort WE, Bressan RA, Lacerda AT. Component mechanisms of executive function in schizophrenia and their contribution to functional outcomes. ACTA ACUST UNITED AC 2018; 41:22-30. [PMID: 30365670 PMCID: PMC6781696 DOI: 10.1590/1516-4446-2018-0021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 03/26/2018] [Indexed: 11/22/2022]
Abstract
OBJECTIVE In schizophrenia, scores reflecting deficits in different cognitive processes are strongly correlated, making it difficult to establish a solid relationship between different cognitive mechanisms and other features of this disorder. The objective of this study was to explore whether three frequently postulated executive functions (updating, shifting, and inhibition) could be compared between groups and considered independently in terms of their respective roles in functional outcome. METHODS This study relied on confirmatory factor analysis of schizophrenia patients (n=141) and healthy controls (n=119). The main analyses examined the degree to which three executive functions (updating, set-shifting, and inhibition) could be separated in schizophrenia and compared this model among groups. Structural equation modeling analysis was also performed to examine the extent to which executive function components contribute to functional outcome in schizophrenia. RESULTS Multiple-group confirmatory factor analysis with unconstrained model parameters indicated that the full three-factor model may fit the data in both groups (χ2 = 61.48, degrees of freedom = 34, p < 0.001, comparative fit index = 0.95; standardized root mean square residual = 0.037; root mean square error of approximation = 0.04; Akaike's information criteria = 169.49; normed fit index = 0.90), although there was also a good data fit for the patient group with a two-factor model. In the patient group, structural equation modeling suggested that shifting and (principally) updating were associated with the general measure of functional outcome (regression path coefficients: 0.34, p < 0.005; 0.39, p < 0.005, respectively), although when combined the mechanisms fail to contribute. CONCLUSION This data suggests that the factor structure may be similar but not identical between groups, and both updating and shifting may play an important role in functional outcome in schizophrenia.
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Affiliation(s)
- Arthur A Berberian
- Programa de Esquizofrenia (PROESQ), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | - Ary Gadelha
- Programa de Esquizofrenia (PROESQ), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | - Natália M Dias
- Programa de Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie, São Paulo, SP, Brazil.,Departamento de Psicologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC, Brazil
| | - Tatiana P Mecca
- Programa de Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie, São Paulo, SP, Brazil
| | - William E Comfort
- Programa de Distúrbios do Desenvolvimento, Universidade Presbiteriana Mackenzie, São Paulo, SP, Brazil
| | - Rodrigo A Bressan
- Programa de Esquizofrenia (PROESQ), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.,Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Acioly T Lacerda
- Programa de Esquizofrenia (PROESQ), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
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