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Rossier AT, Hallahan B. The therapeutic effect of omega-3 polyunsaturated fatty acids on symptom severity of psychosis: A systematic review and meta-analysis. Eur Psychiatry 2024; 67:e88. [PMID: 39697115 PMCID: PMC11733620 DOI: 10.1192/j.eurpsy.2024.1804] [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: 07/19/2024] [Revised: 11/10/2024] [Accepted: 11/16/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND While omega-3 polyunsaturated fatty acids (PUFAs) have shown promise as an adjunctive treatment for schizophrenia and other psychotic disorders, the overall consensus about their efficacy across studies is still lacking and findings to date are inconclusive. No clinical trials or systematic reviews have yet examined if omega-3 PUFAs are associated with differential levels of efficacy at various stages of psychosis. METHOD A systematic bibliographic search of randomized double-blind placebo-controlled trials (RCTs) examining the effect of omega-3 PUFAs as a monotherapy or adjunctive therapy versus a control group in adults and children at ultra-high risk (UHR) for psychosis, experiencing a first-episode psychosis (FEP), or diagnosed with an established psychotic disorder was conducted. Participants' clinical symptoms were evaluated using total and subscale scores on validated psychometric scales. RESULTS No beneficial effect of omega-3 PUFAs treatment was found in comparison with that of placebo (G = -0.26, 95% CI -0.55 to 0.03, p = 0.08). Treatment of omega-3 PUFAs did not prove any significant improvement in psychopathology in UHR (G = -0.09, 95% CI -0.45 to 0.27, p = 0.63), FEP (G = -1.20, 95% CI -5.63 to 3.22, p = 0.59), or schizophrenia patients (G = -0.17, 95% CI -0.38 to -0.03, p = 0.10). CONCLUSION These findings confirm previous evidence that disputes the original reported findings of the beneficial effect of omega-3 PUFAs in schizophrenia. Furthermore, accumulative evidence of the use of omega-3 as a preventive treatment option in UHR is not supported, suggesting that the need for future studies in this line of research should not be promoted.
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Affiliation(s)
- Alison T. Rossier
- Department of Pharmacology and Therapeutics, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland
| | - Brian Hallahan
- Department of Psychiatry, College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland
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Fond G, Mallet J, Urbach M, Benros ME, Berk M, Billeci M, Boyer L, Correll CU, Fornaro M, Kulkarni J, Leboyer M, Llorca PM, Misdrahi D, Rey R, Schürhoff F, Solmi M, Sommer IEC, Stahl SM, Pignon B, Berna F. Adjunctive agents to antipsychotics in schizophrenia: a systematic umbrella review and recommendations for amino acids, hormonal therapies and anti-inflammatory drugs. BMJ MENTAL HEALTH 2023; 26:e300771. [PMID: 37852631 PMCID: PMC10583081 DOI: 10.1136/bmjment-2023-300771] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/02/2023] [Indexed: 10/20/2023]
Abstract
QUESTION This umbrella review and guidelines aimed to provide evidence to support the rational choice of selected adjunctive therapies for schizophrenia. STUDY SELECTION AND ANALYSIS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and World Federation of Societies of Biological Psychiatry (WFSBP)-grading recommendations, 63 randomised control trials (RCTs) (of which 4219 unique participants have completed the RCTs) and 29 meta-analyses were analysed. FINDINGS Provisional recommendations (WFSBP-grade 1) could be made for two molecules in augmentation to antipsychotics: (1) N-acetyl-cysteine (NAC, 1200-3600 mg/day, for >12 consecutive weeks) in improving negative symptoms, general psychopathology (positive and negative syndrome scale for schizophrenia (PANSS) general psychopathology factor (G)-G subscale), with the RCTs with the longer duration showing the most robust findings; (2) polyunsaturated fatty acids (3000 mg/day of eicosapentaenoic acid, for >12 weeks) in improving general psychopathology. Weaker recommendations (ie, WFSBP-grade 2) could be drawn for sarcosine (2 g/day) and minocycline (200-300 mg/day) for improving negative symptoms in chronic schizophrenia (not early schizophrenia), and NAC for improving positive symptoms and cognition. Weak recommendations are not ready for clinical practice. There is provisional evidence that oestrogens and raloxifene are effective in some patients, but further research is needed to determine their benefit/risk ratio. CONCLUSIONS The results of this umbrella review should be interpreted with caution as the number of RCTs included in the meta-analyses was generally small and the effect sizes were weak or medium. For NAC, two RCTs with low risk of bias have provided conflicting results and the WFSBP-grade recommendation included also the results of meta-analyses. These drugs could be provisionally prescribed for patients for whom no other treatments have been effective, but they should be discontinued if they prove ineffective.
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Affiliation(s)
- Guillaume Fond
- Department of psychiatry, Assistance Publique des Hôpitaux de Marseille, Marseille, France
- Fondation FondaMental, Creteil, France
- CEReSS-Health Service Research and Quality of Life Center, AMU, Marseille, France
| | - Jasmina Mallet
- Fondation FondaMental, Creteil, France
- Department of Psychiatry, Louis Mourier Hospital, Colombes, France
| | - Mathieu Urbach
- Fondation FondaMental, Creteil, France
- Department of Adult Psychiatry and Addictology, Centre Hospitalier de Versailles, Le Chesnay, France
| | - Michael Eriksen Benros
- Copenhagen Research Center for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Michael Berk
- Deakin University, School of Medicine, and Barwon Health; IMPACT, the Institute for Mental and Physical Health and Clinical Translation; Orygen The National Centre of Excellence in Youth Mental Health, The Florey Institute of Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne and the Department of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
| | - Martina Billeci
- Department of Neuroscience, Reproductive Sciences, and Dentistry, Section of Psychiatry, Federico II University of Naples, Naples, Italy
| | - Laurent Boyer
- CEReSS-Health Service Research and Quality of Life Center, AMU, Marseille, France
- Département d'information médicale, Assistance Publique des Hôpitaux de Marseille, Marseille, France
| | - Christoph U Correll
- Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York, USA
- Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany
- German Center for Mental Health (DZPG), partner site Berlin, Berlin, Germany
| | - Michele Fornaro
- Department of Neuroscience, Reproductive Sciences, and Dentistry, Section of Psychiatry, Federico II University of Naples, Naples, Italy
| | - Jayashri Kulkarni
- Department of Psychiatry, Monash Alfred Psychiatry Research Centre, Alfred Hospital and Monash University Central Clinical School, Monash University,607StKildaRd, Level4, Melbourne, Victoria, Australia 3004, Melbourne, Victoria, Australia
| | - Marion Leboyer
- Fondation FondaMental, Creteil, France
- Department of psychiatry, Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires « H. Mondor », DMU IMPACT, INSERM U955, IMRB, translational Neuropsychiatry, F-94010 Creteil, France, Créteil, France
| | - Pierre-Michel Llorca
- Fondation FondaMental, Creteil, France
- Département de psychiatrie, Université Clermont Auvergne, CMP-B CHU, CNRS,Clermont Auvergne INP, Institut Pascal, Clermont-Ferrand, France
| | - David Misdrahi
- Fondation FondaMental, Creteil, France
- Departement de Psychiatrie Générale et Universitaire, Centre Hospitalier Charles Perrens; Univ. Bordeaux, CNRS, UMR 5287, F-33000, INCIA, Bordeaux, France
| | - Romain Rey
- Fondation FondaMental, Creteil, France
- Schizophrenia Expert Centre, Le Vinatier Hospital; INSERM, U1028; CNRS, UMR5292; University Lyon 1; Lyon Neuroscience Research Center, PSYR2 Team, Lyon, France
| | - Franck Schürhoff
- Fondation FondaMental, Creteil, France
- Department of psychiatry, Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires « H. Mondor », DMU IMPACT, INSERM U955, IMRB, translational Neuropsychiatry, F-94010 Creteil, France, Créteil, France
| | - Marco Solmi
- Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada
- Department of Mental Health, The Champlain First Episode Psychosis Program, The Ottawa Hospital, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute (OHRI) Clinical Epidemiology Program University of Ottawa, Ottawa Hospital Research Institute (OHRI), Ottawa, Ontario, Canada
- Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany
| | - Iris E C Sommer
- Department of Psychiatry, University Medical Center Groningen (UMCG), Groningen, The Netherlands
| | - Stephen M Stahl
- Department of Psychiatry, University of California, San Diego, California, USA
| | - Baptiste Pignon
- Fondation FondaMental, Creteil, France
- Department of psychiatry, Univ Paris-Est-Créteil (UPEC), AP-HP, Hôpitaux Universitaires « H. Mondor », DMU IMPACT, INSERM U955, IMRB, translational Neuropsychiatry, F-94010 Creteil, France, Créteil, France
| | - Fabrice Berna
- Fondation FondaMental, Creteil, France
- Psychiatry, Strasbourg University Hospital, University of Strasbourg, Strasbourg, France
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3
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Orbe EB, Benros ME. Immunological Biomarkers as Predictors of Treatment Response in Psychotic Disorders. J Pers Med 2023; 13:1382. [PMID: 37763150 PMCID: PMC10532612 DOI: 10.3390/jpm13091382] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/05/2023] [Accepted: 09/10/2023] [Indexed: 09/29/2023] Open
Abstract
Psychotic disorders, notably schizophrenia, impose a detrimental burden on both an individual and a societal level. The mechanisms leading to psychotic disorders are multifaceted, with genetics and environmental factors playing major roles. Increasing evidence additionally implicates neuro-inflammatory processes within at least a subgroup of patients with psychosis. While numerous studies have investigated anti-inflammatory add-on treatments to current antipsychotics, the exploration of immunological biomarkers as a predictor of treatment response remains limited. This review outlines the current evidence from trials exploring the potential of baseline inflammatory biomarkers as predictors of the treatment effect of anti-inflammatory drugs as add-ons to antipsychotics and of antipsychotics alone. Several of the studies have found correlations between baseline immunological biomarkers and treatment response; however, only a few studies incorporated baseline biomarkers as a primary endpoint, and the findings thus need to be interpreted with caution. Our review emphasizes the need for additional research on the potential of repurposing anti-inflammatory drugs while utilizing baseline inflammatory biomarkers as a predictor of treatment response and to identify subgroups of individuals with psychotic disorders where add-on treatment with immunomodulating agents would be warranted. Future studies investigating the correlation between baseline inflammatory markers and treatment responses can pave the way for personalized medicine approaches in psychiatry centred around biomarkers such as specific baseline inflammatory biomarkers in psychotic disorders.
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Affiliation(s)
- Elif Bayram Orbe
- Copenhagen Research Centre for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, 2900 Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1172 Copenhagen, Denmark
| | - Michael Eriksen Benros
- Copenhagen Research Centre for Biological and Precision Psychiatry, Mental Health Centre Copenhagen, Copenhagen University Hospital, 2900 Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1172 Copenhagen, Denmark
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4
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Adrien V, Bosc N, Fumat H, Tessier C, Ferreri F, Mouchabac S, Tareste D, Nuss P. Higher stress response and altered quality of life in schizophrenia patients with low membrane levels of docosahexaenoic acid. Front Psychiatry 2023; 14:1089724. [PMID: 36816405 PMCID: PMC9937080 DOI: 10.3389/fpsyt.2023.1089724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 01/12/2023] [Indexed: 02/05/2023] Open
Abstract
Schizophrenia is a severe, chronic, and heterogeneous mental disorder that affects approximately 1% of the world population. Ongoing research aims at clustering schizophrenia heterogeneity into various "biotypes" to identify subgroups of individuals displaying homogeneous symptoms, etiopathogenesis, prognosis, and treatment response. The present study is in line with this approach and focuses on a biotype partly characterized by a specific membrane lipid composition. We have examined clinical and biological data of patients with stabilized schizophrenia, including the fatty acid content of their erythrocyte membranes, in particular the omega-3 docosahexaenoic acid (DHA). Two groups of patients of similar size were identified: the DHA- group (N = 19) with a lower proportion of membrane DHA as compared to the norm in the general population, and the DHAn group (N = 18) with a normal proportion of DHA. Compared to DHAn, DHA- patients had a higher number of hospitalizations and a lower quality of life in terms of perceived health and physical health. They also exhibited significant higher interleukin-6 and cortisol blood levels. These results emphasize the importance of measuring membrane lipid and immunoinflammatory biomarkers in stabilized patients to identify a specific subgroup and optimize non-pharmacological interventions. It could also guide future research aimed at proposing specific pharmacological treatments.
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Affiliation(s)
- Vladimir Adrien
- AP-HP, Sorbonne Université, Department of Psychiatry, Hôpital Saint-Antoine, Paris, France.,Infrastructure for Clinical Research in Neurosciences (iCRIN), Paris Brain Institute, Sorbonne Université, INSERM, CNRS, Paris, France.,Université Paris Cité, INSERM UMR-S 1266, Institut de Psychiatrie et Neurosciences de Paris, Paris, France
| | - Nicolas Bosc
- AP-HP, Sorbonne Université, Department of Psychiatry, Hôpital Saint-Antoine, Paris, France
| | - Hugo Fumat
- Université Paris Cité, INSERM UMR-S 1266, Institut de Psychiatrie et Neurosciences de Paris, Paris, France
| | - Cédric Tessier
- AP-HP, Sorbonne Université, Department of Psychiatry, Hôpital Saint-Antoine, Paris, France
| | - Florian Ferreri
- AP-HP, Sorbonne Université, Department of Psychiatry, Hôpital Saint-Antoine, Paris, France.,Infrastructure for Clinical Research in Neurosciences (iCRIN), Paris Brain Institute, Sorbonne Université, INSERM, CNRS, Paris, France
| | - Stéphane Mouchabac
- AP-HP, Sorbonne Université, Department of Psychiatry, Hôpital Saint-Antoine, Paris, France.,Infrastructure for Clinical Research in Neurosciences (iCRIN), Paris Brain Institute, Sorbonne Université, INSERM, CNRS, Paris, France
| | - David Tareste
- Université Paris Cité, INSERM UMR-S 1266, Institut de Psychiatrie et Neurosciences de Paris, Paris, France
| | - Philippe Nuss
- AP-HP, Sorbonne Université, Department of Psychiatry, Hôpital Saint-Antoine, Paris, France.,Centre de Recherche Saint-Antoine, INSERM UMR S938, Sorbonne Université, Paris, France
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5
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Abstract
Depression and psychosis have a developmental component to their origin. Epidemiologic evidence, which we synthesize in this nonsystematic review, suggests that early-life infection, inflammation, and metabolic alterations could play a role in the etiology of these psychiatric disorders. The risk of depression and psychosis is associated with prenatal maternal and childhood infections, which could be mediated by impaired neurodevelopment. Evidence suggests linear dose-response associations between elevated concentrations of circulating inflammatory markers in childhood, particularly the inflammatory cytokine interleukin 6, and the risk for depression and psychosis subsequently in early adulthood. Childhood inflammatory markers are also associated with persistence of depressive symptoms subsequently in adolescence and early adulthood. Developmental trajectories reflecting persistently high insulin levels during childhood and adolescence are associated with a higher risk of psychosis in adulthood, whereas increased adiposity during and after puberty is associated with the risk of depression. Together, these findings suggest that higher levels of infection, inflammation, and metabolic alterations commonly seen in people with depression and psychosis could be a cause for, rather than simply a consequence of, these disorders. Therefore, early-life immuno-metabolic alterations, as well as factors influencing these alterations such as adversity or maltreatment, could represent targets for prevention of these psychiatric disorders. Inflammation could also be an important treatment target for depression and psychosis. The field requires further research to examine sensitive periods when exposure to such immuno-metabolic alterations is most harmful. Interventional studies are also needed to test the potential usefulness of targeting early-life immuno-metabolic alterations for preventing adult depression and psychosis.
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6
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Potanin SS, Morozova MA. [Oxidative stress in schizophrenia as a promising target for psychopharmacotherapy]. Zh Nevrol Psikhiatr Im S S Korsakova 2021; 121:131-138. [PMID: 34693701 DOI: 10.17116/jnevro2021121091131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Until now, only dopamine receptor blockers are used for psychopharmacotherapy of schizophrenia, despite the active search for alternative pharmacological agents and a lot of research. However, most of these studies concerned molecules that somehow affect various neurotransmitter receptors. In addition, various anti-inflammatory drugs have been studied quite actively. At the same time, attempts to correct oxidative stress are given significantly less attention, although the emergence of the latter is facilitated by completely different pathophysiological processes and environmental factors associated with the development of schizophrenia. NMDA receptor blockage, vitamin D deficiency, social isolation, chronic stress in adolescence, inflammation, perinatal infection etc. - all this can ultimately lead to the occurrence of oxidative stress. However, there is a significant difference in the severity of this process depending on the stage of the course of schizophrenia, which probably partially explains the heterogeneity of results of the studies on the oxidative stress biomarkers in this disorder. In order to overcome these methodological problems, it seems promising to conduct double-blind studies of the effectiveness of antioxidants in schizophrenia with the selection of groups of patients taking into account the stage of the disorder and the level of certain biomarkers of oxidative stress (F2-isoprostanes, 8-oxodG, 8-oxoGuo). The optimal pharmacological agents for such studies are N-acetylcysteine due to the positive results of previous studies, and melatonin as an antioxidant with a unique activity profile.
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Affiliation(s)
- S S Potanin
- Mental Health Research Center, Moscow, Russia
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7
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Onaolapo OJ, Onaolapo AY. Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment. World J Clin Cases 2021; 9:8295-8311. [PMID: 34754840 PMCID: PMC8554424 DOI: 10.12998/wjcc.v9.i28.8295] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/04/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
Schizophrenia is a mental health disorder that occurs worldwide, cutting across cultures, socioeconomic groups, and geographical barriers. Understanding the details of the neurochemical basis of schizophrenia, factors that contribute to it and possible measures for intervention are areas of ongoing research. However, what has become more evident is the fact that in targeting the neurochemical imbalances that may underlie schizophrenia, the type of response seen with currently available phamacotherapeutic agents does not provide all the answers that are needed. Therefore, the possible contribution of non-pharmacological approaches to schizophrenia management is worthy of consideration. In recent times, research is beginning to show nutrition may play a possibly significant role in schizophrenia, affecting its development, progression and management; however, while attempts had been made to examine this possible relationship from different angles, articles addressing it from a holistic point of view are not common. In this review, we examine existing scientific literature dealing with the possible relationship between nutrition and schizophrenia, with a view to elucidating the impact of diet, nutritional deficiencies and excesses on the aetiology, progression, management and outcome of schizophrenia. Secondly, the effect of nutritional supplements in prevention, as sole therapy, or adjuncts in schizophrenia management are examined.
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Affiliation(s)
- Olakunle James Onaolapo
- Behavioural Neuroscience/Neuropharmacology Unit, Department of Pharmacology, Ladoke Akintola University of Technology, Osun State 234, Nigeria
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Goh KK, Chen CYA, Chen CH, Lu ML. Effects of omega-3 polyunsaturated fatty acids supplements on psychopathology and metabolic parameters in schizophrenia: A meta-analysis of randomized controlled trials. J Psychopharmacol 2021; 35:221-235. [PMID: 33586517 DOI: 10.1177/0269881120981392] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Several monotherapy and augmentation strategies have been introduced to improve the treatment of schizophrenia. The benefits of omega-3 polyunsaturated fatty acids in patients with mental disorders is becoming increasingly acknowledged. However, its role in the treatment of schizophrenia raises complex considerations about which there has been little consensus. The aim of this study was to synthesize the findings of randomized controlled trials that were conducted to determine the efficacy and safety of omega-3 polyunsaturated fatty acids in patients with schizophrenia. METHODS The MEDLINE, Embase, Cochrane, Scopus, and Web of Science databases were searched for relevant literature. The primary outcome was changes in psychopathology and the secondary outcomes were changes in metabolic parameters and safety profiles. RESULTS Twenty double-blind randomized controlled trials in 1494 patients were included. Omega-3 polyunsaturated fatty acids augmentation was associated with significantly improved psychopathology in patients with schizophrenia, particularly general psychopathology and positive symptoms but not negative symptoms. Patients who were severely ill and received omega-3 polyunsaturated fatty acids containing eicosapentaenoic acid >1 g/d showed significant improvement. A favorable effect of omega-3 polyunsaturated fatty acids supplements on serum triglycerides was also demonstrated. Omega-3 polyunsaturated fatty acids are well-tolerated and safe in patients with schizophrenia. CONCLUSIONS These findings tentatively support the use of omega-3 polyunsaturated fatty acids as a potential augmentation strategy in schizophrenia. Further research in larger samples is warranted to clarify the optimal dosage and the correct proportions of omega-3 polyunsaturated fatty acids to administer, together with elucidation of the underlying mechanisms.
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Affiliation(s)
- Kah K Goh
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Cynthia Yi-An Chen
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Chun-Hsin Chen
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Mong-Liang Lu
- Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan.,Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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9
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Adolescent Neurodevelopment and Vulnerability to Psychosis. Biol Psychiatry 2021; 89:184-193. [PMID: 32896384 PMCID: PMC9397132 DOI: 10.1016/j.biopsych.2020.06.028] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 06/23/2020] [Accepted: 06/25/2020] [Indexed: 12/28/2022]
Abstract
Adolescence is characterized by significant changes in several domains, including brain structure and function, puberty, and social and environmental factors. Some of these changes serve to increase the likelihood of psychosis onset during this period, while others may buffer this risk. This review characterizes our current knowledge regarding the unique aspects of adolescence that may serve as risk factors for schizophrenia spectrum disorders. In addition, we provide potential future directions for research into adolescent-specific developmental mechanisms that impart vulnerability to psychosis and the possibility of interventions that capitalize on adolescents' unique characteristics. Specifically, we explore the ways in which gray and white matter develop throughout adolescence in typically developing youth as well as in those with psychosis spectrum disorders. We also discuss current views on the function that social support and demands, as well as role expectations, play in risk for psychosis. We further highlight the importance of considering biological factors such as puberty and hormonal changes as areas of unique vulnerability for adolescents. Finally, we discuss cannabis use as a factor that may have a unique impact during adolescent neurodevelopment, and subsequently potentially impact psychosis onset. Throughout, we include discussion of resilience factors that may provide unique opportunities for intervention during this dynamic life stage.
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10
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Ansarey SH. Inflammation and JNK's Role in Niacin-GPR109A Diminished Flushed Effect in Microglial and Neuronal Cells With Relevance to Schizophrenia. Front Psychiatry 2021; 12:771144. [PMID: 34916973 PMCID: PMC8668869 DOI: 10.3389/fpsyt.2021.771144] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/02/2021] [Indexed: 12/28/2022] Open
Abstract
Schizophrenia is a neuropsychiatric illness with no single definitive aetiology, making its treatment difficult. Antipsychotics are not fully effective because they treat psychosis rather than the cognitive or negative symptoms. Antipsychotics fail to alleviate symptoms when patients enter the chronic stage of illness. Topical application of niacin showed diminished skin flush in the majority of patients with schizophrenia compared to the general population who showed flushing. The niacin skin flush test is useful for identifying patients with schizophrenia at their ultra-high-risk stage, and understanding this pathology may introduce an effective treatment. This review aims to understand the pathology behind the diminished skin flush response, while linking it back to neurons and microglia. First, it suggests that there are altered proteins in the GPR109A-COX-prostaglandin pathway, inflammatory imbalance, and kinase signalling pathway, c-Jun N-terminal kinase (JNK), which are associated with diminished flush. Second, genes from the GPR109A-COX-prostaglandin pathway were matched against the 128-loci genome wide association study (GWAS) for schizophrenia using GeneCards, suggesting that G-coupled receptor-109A (GPR109A) may have a genetic mutation, resulting in diminished flush. This review also suggests that there may be increased pro-inflammatory mediators in the GPR109A-COX-prostaglandin pathway, which contributes to the diminished flush pathology. Increased levels of pro-inflammatory markers may induce microglial-activated neuronal death. Lastly, this review explores the role of JNK on pro-inflammatory mediators, proteins in the GPR109A-COX-prostaglandin pathway, microglial activation, and neuronal death. Inhibiting JNK may reverse the changes observed in the diminished flush response, which might make it a good therapeutic target.
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Affiliation(s)
- Sabrina H Ansarey
- Department of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom
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11
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Jeppesen R, Christensen RHB, Pedersen EMJ, Nordentoft M, Hjorthøj C, Köhler-Forsberg O, Benros ME. Efficacy and safety of anti-inflammatory agents in treatment of psychotic disorders - A comprehensive systematic review and meta-analysis. Brain Behav Immun 2020; 90:364-380. [PMID: 32890697 DOI: 10.1016/j.bbi.2020.08.028] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/07/2020] [Accepted: 08/28/2020] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE Antipsychotic effects of immunomodulating drugs have been suggested; however, a thorough, comprehensive meta-analysis on the effect and safety of anti-inflammatory add-on treatment on psychotic disorders is lacking. METHOD Multiple databases were searched up until February 2020. Only double-blinded, randomized, placebo-controlled clinical trials (RCTs) were included. Primary outcomes were change in total psychopathology and adverse events. Secondary outcomes included, amongst others, positive and negative symptoms, general psychopathology and cognitive domains. We performed random-effects meta-analyses estimating mean differences (MD) and standardized mean differences (SMD) for effect sizes. RESULTS Seventy RCTs (N = 4104) were included, investigating either primarily anti-inflammatory drugs, i.e. drugs developed for immunomodulation, such as NSAIDs, minocycline and monoclonal antibodies (k = 15), or drugs with potential anti-inflammatory properties (k = 55), e.g. neurosteroids, N-acetyl cysteine, estrogens, fatty acids, statins, and glitazones. Antipsychotics plus anti-inflammatory treatment, compared to antipsychotics plus placebo, was associated with a PANSS scale MD improvement of -4.57 (95%CI = -5.93 to -3.20) points, corresponding to a SMD effect size of -0.29 (95%CI = -0.40 to -0.19). Trials on schizophrenia (MD = -6.80; 95%CI, -9.08 to -4.52) showed greater improvement (p < 0.01) than trials also including other psychotic disorders. However, primarily anti-inflammatory drugs (MD = 4.00; 95%CI = -7.19 to -0.80) were not superior (p = 0.69) to potential anti-inflammatory drugs (MD = 4.71; 95%CI = -6.26 to -3.17). Furthermore, meta-regression found that smaller studies showed significantly larger effect sizes than the larger studies (p = 0.0085), and only 2 studies had low risk of bias on all domains. Small but significant effects were found on negative symptoms (MD = -1.29), positive symptoms (MD = -0.53), general psychopathology (MD = -1.50) and working memory (SMD = 0.21). No differences were found regarding adverse events, but only 26 studies reported hereon. CONCLUSIONS Anti-inflammatory add-on treatment to antipsychotics showed improvement of psychotic disorders; however, no superiority was found in primarily anti-inflammatory drugs, raising the question of the mechanism behind the effect, and treatment effect might be overestimated due to the large number of small studies.
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Affiliation(s)
- Rose Jeppesen
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
| | - Rune H B Christensen
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
| | - Emilie M J Pedersen
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark
| | - Merete Nordentoft
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; iPSYCH The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
| | - Carsten Hjorthøj
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; iPSYCH The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; University of Copenhagen, Department of Public Health, Section of Epidemiology, Denmark
| | - Ole Köhler-Forsberg
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Michael E Benros
- Copenhagen Research Center for Mental Health - CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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12
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Alessi MG, Bennett JM. Mental health is the health of the whole body: How psychoneuroimmunology & health psychology can inform & improve treatment. J Eval Clin Pract 2020; 26:1539-1547. [PMID: 32171052 DOI: 10.1111/jep.13386] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Revised: 01/12/2020] [Accepted: 02/20/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Converging and accumulating evidence for the cross-communication among the nervous, immune, and endocrine systems, a field of study known as psychoneuroimmunology, implicates immunological dysfunction as a shared and common mechanism of both mental and physical illness. For example, psychiatric disorders like schizophrenia, bipolar disorder, major depression, and anxiety disorders have higher prevalence rates across a spectrum of autoimmune conditions compared to the general population. Additionally, subclinical immunological abnormalities are observed in a variety of psychiatric conditions, with chronic inflammation most extensively studied in the pathophysiology of depression. These observations blur the historical distinctions between mental and physical illness, yet clinical practice remains fragmented and primarily focused on differentially treating individual symptoms. PROPOSED THESIS Therapeutically targeting inflammation offers translational opportunities for integrating mental and physical healthcare, a key niche of the interdisciplinary field of health psychology. CONCLUSION Utilizing a psychoneuroimmunological lens, health psychologists and clinicians can reconceptualize healthcare through integrative treatment approaches and advocacy for comprehensive policy-level reform at both the individual-level of care as well as community-wide prevention approaches.
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Affiliation(s)
- Maria G Alessi
- Health Psychology PhD Program, UNC Charlotte, Charlotte, North Carolina, USA
| | - Jeanette M Bennett
- Health Psychology PhD Program, UNC Charlotte, Charlotte, North Carolina, USA.,Department of Psychological Science, UNC Charlotte, Charlotte, North Carolina, USA
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13
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Mongan D, Ramesar M, Föcking M, Cannon M, Cotter D. Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment. Early Interv Psychiatry 2020; 14:385-397. [PMID: 31368253 DOI: 10.1111/eip.12859] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 05/13/2019] [Accepted: 07/14/2019] [Indexed: 12/28/2022]
Abstract
AIM Over the past several decades, there has been a growing research interest in the role of inflammation in the pathogenesis of schizophrenia. This review aims to summarize evidence in support of this relationship, to discuss biological mechanisms that might explain it, and to explore the translational impact by examining evidence from trials of anti-inflammatory and immunomodulatory agents in the treatment of schizophrenia. METHODS This narrative review of the literature summarizes evidence from observational studies, clinical trials and meta-analyses to evaluate the role of inflammation in the pathogenesis of schizophrenia and to discuss associated implications for treatment. RESULTS Epidemiological evidence and animal models support a hypothesis of maternal immune activation during pregnancy, which increases the risk of schizophrenia in the offspring. Several biomarker studies have found associations between classical pro-inflammatory cytokines and schizophrenia. The precise biological mechanisms by which inflammatory processes might contribute to the pathogenesis of schizophrenia remain unclear, but likely include the actions of microglia and the complement system. Importantly, several trials provide evidence that certain anti-inflammatory and immunomodulatory agents show beneficial effects in the treatment of schizophrenia. Nevertheless, there is a need for further precision-focused basic science and translational research. CONCLUSIONS Increasing our understanding of the role of inflammation in schizophrenia will enable novel opportunities for therapeutic and preventative interventions that are informed by the underlying pathogenesis of this complex disorder.
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Affiliation(s)
- David Mongan
- Royal College of Surgeons in Ireland, Dublin, Ireland
| | | | | | - Mary Cannon
- Royal College of Surgeons in Ireland, Dublin, Ireland
| | - David Cotter
- Royal College of Surgeons in Ireland, Dublin, Ireland
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Hsu MC, Huang YS, Ouyang WC. Beneficial effects of omega-3 fatty acid supplementation in schizophrenia: possible mechanisms. Lipids Health Dis 2020; 19:159. [PMID: 32620164 PMCID: PMC7333328 DOI: 10.1186/s12944-020-01337-0] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/24/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. METHODS In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed. RESULTS Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention. CONCLUSION Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.
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Affiliation(s)
- Mei-Chi Hsu
- Department of Nursing, I-Shou University, No.8, Yida Road, Jiaosu Village Yanchao District, Kaohsiung, 82445 Taiwan
| | - Yung-Sheng Huang
- College of Medicine, I-Shou University, No.8, Yida Road, Jiaosu Village Yanchao District, Kaohsiung, 82445 Taiwan
| | - Wen-Chen Ouyang
- Department of Geriatric Psychiatry, Jianan Psychiatric Center, Ministry of Health and Welfare, No.539, Yuzhong Rd., Rende Dist., Tainan City, 71742 Taiwan
- Department of Nursing, Shu-Zen Junior College of Medicine and Management, No.452, Huanqiu Rd. Luzhu Dist, Kaohsiung, 82144 Taiwan
- Department of Psychiatry, College of Medicine, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708 Taiwan
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15
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Clinical implications of oxidative stress in schizophrenia: Acute relapse and chronic stable phase. Prog Neuropsychopharmacol Biol Psychiatry 2020; 99:109868. [PMID: 31954755 DOI: 10.1016/j.pnpbp.2020.109868] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 12/03/2019] [Accepted: 01/15/2020] [Indexed: 12/22/2022]
Abstract
Several studies have suggested a higher oxidative stress in schizophrenia. However, the implications of oxidative stress on clinical symptoms remain unclear. This study aimed to investigate the platelet oxidative stress in different stages of schizophrenia (i.e., chronic stable and acute relapse) in order to clarify the clinical implications of oxidative stress and the treatment effects. We recruited 43 chronic stable patients with schizophrenia and 48 non-psychiatric controls. Platelets were collected for measuring the levels of nitric oxide (NO), lipid peroxidation (LPO), and glutathione (GSH) and the activity of GSH peroxidase (GPx) and superoxide dismutase (SOD). The levels and activity were compared between patients and controls and were examined for their relationship with clinical severity. Further, we evaluated the changes of levels and activity before and after treatment in an independent sample with acute relapse (N = 19). Patients with chronic stable schizophrenia had lower SOD activity compared to non-psychiatric controls. In chronic stable patients, NO level was positively correlated with positive and disorganized symptoms, while the GPx activity were negatively correlated with excitement. In patients with acute relapse, the levels and activity were not different before and after four weeks of antipsychotic treatment, but LPO level was negatively correlated with pretreatment disorganized symptoms. The change of LPO can also predict the change of disorganized symptoms and negative symptoms. Our findings suggest that platelet SOD was lower in chronic stable schizophrenia. Platelet LPO may be associated with less disorganized symptoms in acute relapse patients and better treatment response.
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16
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17
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Favorable effects of omega-3 polyunsaturated fatty acids in attentional control and conversion rate to psychosis in 22q11.2 deletion syndrome. Neuropharmacology 2020; 168:107995. [PMID: 32057798 DOI: 10.1016/j.neuropharm.2020.107995] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Revised: 02/05/2020] [Accepted: 02/06/2020] [Indexed: 12/13/2022]
Abstract
Omega-3-polyunsaturated-fatty-acids were suggested against cognitive dysfunctions and conversion to psychosis. However, a recent multicenter trial found no effect in reducing conversion rates in individuals at risk of developing schizophrenia. Patients' genetic heterogeneity and the timing of treatment might influence omega-3 efficacy. Here, we addressed the impact of omega-3 early treatment in both mice and human subjects with a 22q11.2 genetic hemi-deletion (22q11DS), characterized by cognitive dysfunctions and high penetrance of schizophrenia. We first tested the behavioural and cognitive consequences of adolescent exposure to normal or omega-3-enriched diets in wild-type and 22q11DS (LgDel/+) mice. We then contrasted mouse data with those gathered from sixty-two patients with 22q11DS exposed to a normal diet or supplemented with omega-3 during pre-adolescence/adolescence. Adolescent omega-3 exposure had no effects in wild-type mice. However, this treatment ameliorated distractibility deficits revealed in LgDel/+ mice by the Five Choice Serial Reaction Time Task (5CSRTT). The omega-3 improvement in LgDel/+ mice was selective, as no other generalized cognitive and non-cognitive effects were evident. Similarly, omega-3-exposed 22q11DS patients showed long-lasting improvements on distractibility as revealed by the continuous performance test (CPT). Moreover, omega-3-exposed 22q11DS patients showed less risk of developing an Ultra High Risk status and lower conversion rate to psychosis. Our convergent mouse-human findings represent a first analysis on the effects of omega-3 early treatment in 22q11DS. The beneficial effects in attentional control and transition to psychosis could support the early use of omega-3 supplementation in the 22q11DS population.
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18
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Beasley CL, Honer WG, Ramos-Miguel A, Vila-Rodriguez F, Barr AM. Prefrontal fatty acid composition in schizophrenia and bipolar disorder: Association with reelin expression. Schizophr Res 2020; 215:493-498. [PMID: 28583708 DOI: 10.1016/j.schres.2017.05.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2017] [Revised: 05/23/2017] [Accepted: 05/26/2017] [Indexed: 12/31/2022]
Abstract
OBJECTIVE The extracellular matrix protein reelin regulates early brain development and synaptic plasticity in adulthood. Reelin is decreased in the postmortem brain in schizophrenia patients. Reelin's two receptors, ApoER2 and VLDLR, are also substrates for ApoE - a key lipoprotein that regulates phospholipid homeostasis in the brain. The goal of the present study was therefore to examine phospholipids and their constituent fatty acids, and determine whether there is an association between reelin, its receptors and phospholipids in the brain. METHODS Dorsolateral prefrontal cortex (BA9) grey matter was obtained from the Stanley Foundation Neuropathology Consortium. Samples included tissue from 35 controls, 35 schizophrenia and 34 bipolar disorder patients. Phospholipids were measured using gas liquid chromatography. RESULTS We quantified 15 individual fatty acid or plasmalogen species for phosphatidylethanolamine and phosphatidylcholine fractions, each comprising >0.5% of the total fatty acid pool. There were no group differences in phospholipids or individual fatty acid species after correcting for multiple comparisons. However, for the entire cohort, both the polyunsaturated subclass of fatty acids, and ApoE, correlated significantly with reelin expression, with a number of individual ω-6 fatty acid species also demonstrating a significant positive correlation. There was a non-significant trend for similar effects with VLDLR expression as for reelin. CONCLUSION Phospholipids and fatty acids in the dorsolateral cortex do not differ in patients with schizophrenia, bipolar disorder and controls. Reelin expression in this brain region is associated with polyunsaturated fatty acids and ApoE, suggesting further study of potential physiological interactions between these substrates is warranted.
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Affiliation(s)
- Clare L Beasley
- Department of Psychiatry, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada
| | - William G Honer
- Department of Psychiatry, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada
| | - Alfredo Ramos-Miguel
- Department of Psychiatry, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada
| | - Fidel Vila-Rodriguez
- Department of Psychiatry, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada
| | - Alasdair M Barr
- Department of Pharmacology, 2176 Health Sciences Mall, University of British Columbia, Vancouver, B.C. V6T 1Z3, Canada.
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19
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Trageser KJ, Sebastian-Valverde M, Naughton SX, Pasinetti GM. The Innate Immune System and Inflammatory Priming: Potential Mechanistic Factors in Mood Disorders and Gulf War Illness. Front Psychiatry 2020; 11:704. [PMID: 32848904 PMCID: PMC7396635 DOI: 10.3389/fpsyt.2020.00704] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Accepted: 07/03/2020] [Indexed: 12/17/2022] Open
Abstract
Gulf War Illness is a chronic multisystem disorder affecting approximately a third of the Veterans of the Gulf War, manifesting with physical and mental health symptoms such as cognitive impairment, neurological abnormalities, and dysregulation of mood. Among the leading theories into the etiology of this multisystem disorder is environmental exposure to the various neurotoxins encountered in the Gulf Theatre, including organophosphates, nerve agents, pyridostigmine bromide, smoke from oil well fires, and depleted uranium. The relationship of toxin exposure and the pathogenesis of Gulf War Illness converges on the innate immune system: a nonspecific form of immunity ubiquitous in nature that acts to respond to both exogenous and endogenous insults. Activation of the innate immune system results in inflammation mediated by the release of cytokines. Cytokine mediated neuroinflammation has been demonstrated in a number of psychiatric conditions and may help explain the larger than expected population of Gulf War Veterans afflicted with a mood disorder. Several of the environmental toxins encountered by soldiers during the first Gulf War have been shown to cause upregulation of inflammatory mediators after chronic exposure, even at low levels. This act of inflammatory priming, by which repeated exposure to chronic subthreshold insults elicits robust responses, even after an extended period of latency, is integral in the connection of Gulf War Illness and comorbid mood disorders. Further developing the understanding of the relationship between environmental toxin exposure, innate immune activation, and pathogenesis of disease in the Gulf War Veterans population, may yield novel therapeutic targets, and a greater understanding of disease pathology and subsequently prevention.
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Affiliation(s)
- Kyle J Trageser
- Department of Neurology, Mount Sinai School of Medicine, New York, NY, United States
| | | | - Sean X Naughton
- Department of Neurology, Mount Sinai School of Medicine, New York, NY, United States
| | - Giulio Maria Pasinetti
- Department of Neurology, Mount Sinai School of Medicine, New York, NY, United States.,Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical Center, Bronx, NY, United States
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20
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Pakiet A, Jakubiak A, Czumaj A, Sledzinski T, Mika A. The effect of western diet on mice brain lipid composition. Nutr Metab (Lond) 2019; 16:81. [PMID: 31788013 PMCID: PMC6880556 DOI: 10.1186/s12986-019-0401-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Accepted: 10/10/2019] [Indexed: 12/19/2022] Open
Abstract
Background The appropriate fatty acids composition of brain lipids is critical for functioning of this organ. The alterations of brain fatty acids composition may lead to neurological and neurodegenerative diseases. Methods The aim of this work was to evaluate the effect of western diet containing high fat content on fatty acid composition of brain lipids. In this study we used mice fed high fat diet (HFD) for 19 weeks. Brain lipids were separated by SPE extraction and fatty acid composition in chow, mice serum, brain and other tissues was analyzed by GC-MS method. Results The body weight and adipose tissue weigh of mice after HFD increased significantly. The concentrations of most of fatty acids in serum of mice after HFD increased, due to their higher delivery from food. Unexpectedly the serum eicosapentaenoic acid (EPA) concentration was lower in mice after HFD than in controls. Also the brain, and other tissue EPA content was lower. Among studied groups of brain lipids EPA was significantly decreased in phospholipids and sphingolipids. Conclusions Considering important role of brain EPA including maintaining of appropriate composition of cell membrane lipids and anti-inflammatory properties we conclude that decrease of brain EPA after western diet may result in impaired brain function.
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Affiliation(s)
- Alicja Pakiet
- 1Department of Environmental Analytics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
| | - Agnieszka Jakubiak
- 2Tri-City Academic Laboratory Animal Centre - Research & Services Centre, Medical University of Gdansk, Gdansk, Poland
| | - Aleksandra Czumaj
- 3Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland
| | - Tomasz Sledzinski
- 3Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland
| | - Adriana Mika
- 1Department of Environmental Analytics, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.,3Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Debinki 1, 80-211 Gdansk, Poland
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Bozzatello P, Rocca P, Mantelli E, Bellino S. Polyunsaturated Fatty Acids: What is Their Role in Treatment of Psychiatric Disorders? Int J Mol Sci 2019; 20:E5257. [PMID: 31652770 PMCID: PMC6862261 DOI: 10.3390/ijms20215257] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Revised: 10/21/2019] [Accepted: 10/22/2019] [Indexed: 12/12/2022] Open
Abstract
In the central nervous system omega-3 fatty acids modulate cell signaling and affect dopaminergic and serotonergic pathways. On this basis, a new application for omega-3 fatty acids has been proposed, concerning the treatment of several psychiatric disorders. The present article is an update of a previous systematic review and is aimed to provide a complete report of data published in the period between 1980 and 2019 on efficacy and tolerability of omega-3 fatty acids in psychiatric disorders. In July 2019, an electronic search on PUBMED, Medline and PsychINFO of all RCTs, systematic reviews and meta-analyses on omega-3 fatty acids and psychiatric disorders without any filter or MESH restriction was performed. After eligibility processes, the final number of records included in this review was 126. One hundred and two of these studies were RCTs, while 24 were reviews and meta-analyses. The role of omega-3 fatty acids was studied in schizophrenia, major depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, eating disorders, substance use disorder and borderline personality disorder. The main evidence of the efficacy of omega-3 fatty acids has been obtained in treating depressive symptoms in patients with major depression and, to a lesser degree, bipolar depression. Some efficacy was also found in early phases of schizophrenia in addition to antipsychotic treatment, but not in the chronic phases of psychosis. Small beneficial effects of omega-3 fatty acids were observed in ADHD and positive results were reported in a few trials on core symptoms of borderline personality disorder. For other psychiatric disorders results are inconsistent.
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Affiliation(s)
- Paola Bozzatello
- Department of Neuroscience, University of Turin, 10125 Turin, Italy.
| | - Paola Rocca
- Department of Neuroscience, University of Turin, 10125 Turin, Italy.
| | - Emanuela Mantelli
- Department of Neuroscience, University of Turin, 10125 Turin, Italy.
| | - Silvio Bellino
- Department of Neuroscience, University of Turin, 10125 Turin, Italy.
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Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, Veronese N, Schuch F, Smith L, Solmi M, Carvalho AF, Vancampfort D, Berk M, Stubbs B, Sarris J. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry 2019; 18:308-324. [PMID: 31496103 PMCID: PMC6732706 DOI: 10.1002/wps.20672] [Citation(s) in RCA: 112] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.
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Affiliation(s)
- Joseph Firth
- NICM Health Research InstituteWestern Sydney UniversityWestmeadAustralia,Division of Psychology and Mental Health, Faculty of Biology, Medicine and HealthUniversity of ManchesterManchesterUK,Centre for Youth Mental HealthUniversity of MelbourneMelbourneAustralia
| | - Scott B. Teasdale
- School of Psychiatry, Faculty of MedicineUniversity of New South WalesSydneyAustralia,Keeping the Body in Mind ProgramSouth Eastern Sydney Local Health DistrictSydneyAustralia
| | - Kelly Allott
- Centre for Youth Mental HealthUniversity of MelbourneMelbourneAustralia,Orygen, The National Centre of Excellence in Youth Mental HealthParkvilleAustralia
| | - Dan Siskind
- Metro South Addiction and Mental Health ServiceBrisbaneAustralia,School of MedicineUniversity of QueenslandBrisbaneAustralia
| | - Wolfgang Marx
- IMPACT Strategic Research Centre, School of MedicineDeakin University, Barwon HealthAustralia
| | | | - Nicola Veronese
- Neuroscience InstituteNational Research CouncilPaduaItaly,Research Hospital, National Institute of GastroenterologyIRCCS De Bellis, Castellana GrotteBariItaly
| | - Felipe Schuch
- Department of Sports Methods and TechniquesFederal University of Santa MariaSanta MariaBrazil
| | - Lee Smith
- Cambridge Centre for Sport and Exercise SciencesAnglia Ruskin UniversityCambridgeUK
| | - Marco Solmi
- Department of NeurosciencesUniversity of PaduaPaduaItaly,Padua Neuroscience CenterUniversity of PaduaPaduaItaly
| | - André F. Carvalho
- Centre for Addiction and Mental HealthTorontoONCanada,Department of PsychiatryUniversity of TorontoTorontoONCanada
| | - Davy Vancampfort
- KU Leuven Department of Rehabilitation SciencesLeuvenBelgium,University Psychiatric Centre KU LeuvenKortenbergBelgium
| | - Michael Berk
- Orygen, The National Centre of Excellence in Youth Mental HealthParkvilleAustralia,IMPACT Strategic Research Centre, School of MedicineDeakin University, Barwon HealthAustralia
| | - Brendon Stubbs
- South London and Maudsley NHS Foundation TrustLondonUK,Institute of Psychiatry, Psychology and NeuroscienceKing's College LondonLondonUK
| | - Jerome Sarris
- NICM Health Research InstituteWestern Sydney UniversityWestmeadAustralia,Professional Unit, The Melbourne Clinic, Department of PsychiatryUniversity of MelbourneMelbourneAustralia
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Nguyen N, Dow M, Woodside B, German JB, Quehenberger O, Shih PAB. Food-Intake Normalization of Dysregulated Fatty Acids in Women with Anorexia Nervosa. Nutrients 2019; 11:E2208. [PMID: 31540208 PMCID: PMC6769727 DOI: 10.3390/nu11092208] [Citation(s) in RCA: 3] [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: 08/03/2019] [Revised: 09/05/2019] [Accepted: 09/08/2019] [Indexed: 12/15/2022] Open
Abstract
Anorexia nervosa (AN) is a psychiatric disorder affected by psychological, environmental, and biological factors. Individuals with AN avoid high-fat, high-calorie diets and have shown abnormal metabolism of fatty acids (FAs), which are essential for brain and cognitive/neuropsychiatric health. To clarify the relationship between FAs and AN, fasting and postprandial plasma FAs in AN patients and age-matched control women were analyzed via mass-spectrometry. Clinical phenotypes were assessed using Becker Anxiety Inventory and Becker Depression Inventory. AN patients and controls exhibited different FA signatures at both fasting and postprandial timepoints. Lauric acid, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and alpha-linoleic acid (ALA) were higher in AN than in controls (lauric acid: 15,081.6 ± 14,970.2 vs. 8257.4 ± 4740.2 pmol/mL; ALA at fasting: 2217.7 ± 1587.6 vs. 1087.9 ± 821.2 pmol/mL; ALA at postprandial: 1830.9 ± 1115.6 vs. 1159.4 ± 664.7 pmol/mL. EPA: 33,788.3 ± 17,487.5 vs. 22,860.6 ± 12,642.4 pmol/mL; DPA: 32,664.8 ± 16,215.0 vs. 20,969.0 ± 12,350.0 pmol/mL. FDR-adjusted p-values < 0.05). Food intake and AN status modified the correlations of FAs with body mass index (BMI), depression, and anxiety. Desaturases SCD-18 and D6D showed lower activities in AN compared to controls. Altered FA signature, specifically correlations between elevated n-3 FAs and worsened symptoms, illustrate metabolic underpinnings in AN. Future studies should investigate the mechanisms by which FA dysregulation, specifically elevated n-3 FAs, affects AN risk and outcome.
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Affiliation(s)
- Nhien Nguyen
- Department of Psychiatry, School of Medicine University of California, San Diego, La Jolla, CA 92037, USA.
| | - Michelle Dow
- Division of Medical Genetics, Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
| | - Blake Woodside
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 2S8, Canada.
| | - J Bruce German
- Department of Food Science & Technology, University of California, Davis, Davis, CA 95616, USA.
| | - Oswald Quehenberger
- Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA.
| | - Pei-An Betty Shih
- Department of Psychiatry, School of Medicine University of California, San Diego, La Jolla, CA 92037, USA.
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Nasir M, Bloch MH. Trim the fat: the role of omega-3 fatty acids in psychopharmacology. Ther Adv Psychopharmacol 2019; 9:2045125319869791. [PMID: 31489174 PMCID: PMC6713969 DOI: 10.1177/2045125319869791] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 07/22/2019] [Indexed: 12/21/2022] Open
Abstract
The American Psychiatric Association (APA) currently recommends the use of omega-3 fatty acid supplementation for depressive disorders, impulse-control disorders, and psychotic disorders in treatment guidelines. This review examines the evidence for efficacy of omega-3 fatty acids in depressive disorders, bipolar disorder, anxiety disorders, post-traumatic stress disorder (PTSD), and psychosis. Meta-analysis of randomized-controlled trials of omega-3 fatty acids for depression are inconclusive, with strong evidence of publication bias, sizable heterogeneity between included studies, and substantial methodological shortcomings in included trials. The large amount of heterogeneity in findings of RCTs of omega-3 fatty acids for unipolar depression is likely attributable to highly heterogeneous sample populations that are given different omega-3 supplements [which differ widely in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, ratio, and dosage] as either adjunctive or monotherapy of other existing treatments, and then measure several different outcomes of depression symptomatology with likely incomplete blinding. Evidence of efficacy of omega-3 supplementation in treating psychosis, PTSD, anxiety, and bipolar mania is minimal. The current guidelines recommending the use of omega-3 fatty acids in adulthood psychiatric conditions should be revisited, especially given several recent negative studies examining the effects of omega-3 fatty acids for cardiovascular disease. Recommending likely ineffective treatment to patients, no matter how benign the side-effect profile, has opportunity cost (e.g. other more effective medications or therapies not being utilized) and likely affects patient compliance with other evidence-based treatments.
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Affiliation(s)
- Madeeha Nasir
- Child Study Center, Yale University School of Medicine, New Haven, CT, USA
| | - Michael H. Bloch
- Child Study Center, Yale University School of Medicine, 230 S. Frontage Road, New Haven, CT, 06520, USA
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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25
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Mazza M, Marano G, Traversi G, Mazza S, Janiri L. Neurobiological Meaning of Omega-3 Fatty Acids and Their Potential Role in the Treatment of Schizophrenia. OMEGA FATTY ACIDS IN BRAIN AND NEUROLOGICAL HEALTH 2019:275-294. [DOI: 10.1016/b978-0-12-815238-6.00018-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/23/2025]
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Aucoin M, LaChance L, Cooley K, Kidd S. Diet and Psychosis: A Scoping Review. Neuropsychobiology 2018; 79:20-42. [PMID: 30359969 DOI: 10.1159/000493399] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 08/29/2018] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for intervention in many physical illnesses and more recently in mental illnesses such as unipolar depression; however, no dietary guidelines exist for patients with SSD. OBJECTIVE This review sought to systematically scope the existing literature in order to identify nutritional interventions for the prevention or treatment of mental health symptoms in SSD as well as gaps and opportunities for further research. METHODS This review followed established methodological approaches for scoping reviews including an extensive a priori search strategy and duplicate screening. Because of the large volume of results, an online program (Abstrackr) was used for screening and tagging. Data were extracted based on the dietary constituents and analyzed. RESULTS Of 55,330 results identified by the search, 822 studies met the criteria for inclusion. Observational evidence shows a connection between the presence of psychotic disorders and poorer quality dietary patterns, higher intake of refined carbohydrates and total fat, and lower intake or levels of fibre, ω-3 and ω-6 fatty acids, vegetables, fruit, and certain vitamins and minerals (vitamin B12 and B6, folate, vitamin C, zinc, and selenium). Evidence illustrates a role of food allergy and sensitivity as well as microbiome composition and specific phytonutrients (such as L-theanine, sulforaphane, and resveratrol). Experimental studies have demonstrated benefit using healthy diet patterns and specific vitamins and minerals (vitamin B12 and B6, folate, and zinc) and amino acids (serine, lysine, glycine, and tryptophan). DISCUSSION Overall, these findings were consistent with many other bodies of knowledge about healthy dietary patterns. Many limitations exist related to the design of the individual studies and the ability to extrapolate the results of studies using dietary supplements to dietary interventions (food). Dietary recommendations are presented as well as recommendations for further research including more prospective observational studies and intervention studies that modify diet constituents or entire dietary patterns with statistical power to detect mental health outcomes.
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Affiliation(s)
- Monique Aucoin
- Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada,
| | - Laura LaChance
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada
- University of Toronto, Toronto, Ontario, Canada
| | - Kieran Cooley
- Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada
- Australian Research Centre in Complementary and Integrative Medicine, University of Technology, Sydney, New South Wales, Australia
| | - Sean Kidd
- Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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Firth J, Rosenbaum S, Ward PB, Curtis J, Teasdale SB, Yung AR, Sarris J. Adjunctive nutrients in first-episode psychosis: A systematic review of efficacy, tolerability and neurobiological mechanisms. Early Interv Psychiatry 2018; 12:774-783. [PMID: 29561067 PMCID: PMC6175456 DOI: 10.1111/eip.12544] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 11/08/2017] [Accepted: 02/04/2018] [Indexed: 12/25/2022]
Abstract
AIM The effects of nutrient-based treatments, including adjunctive vitamin or antioxidant supplementation, have been explored extensively in long-term schizophrenia. However, no systematic evaluation of trials in "first-episode psychosis" (FEP) has been conducted, despite the potential benefits of using these treatments during the early stages of illness. Therefore, we aimed to review all studies examining efficacy, tolerability and the biological mechanisms of action, of nutrient supplementation in FEP. METHODS A systematic review of electronic databases was conducted from inception to July 2017. All information on feasibility, clinical outcomes and mechanistic findings from nutrient supplementation clinical trials was extracted and systematically synthesized. RESULTS Eleven studies with a total of 451 patients with FEP (from 8 independent randomized controlled trials) were eligible for inclusion. Six studies examined omega-3 fatty acids, with inconsistent effects on psychiatric symptoms. However, mechanistic studies found significant improvements in hippocampal neuronal health and brain glutathione. Antioxidants "n-acetyl cysteine" (n = 1) and vitamin C (n = 2) also improved oxidative status in FEP, which was associated with reduced psychiatric symptoms. No benefits were found for vitamin E (n = 1). Finally, one study trialling the amino acid taurine, showed significant improvements in positive symptoms and psychosocial functioning. CONCLUSION There is preliminary evidence that taurine improves outcomes in FEP, whereas effects of omega-3 and antioxidant vitamins/amino-acids are inconsistent; perhaps mainly benefitting patients with high levels of oxidative stress. Future studies should evaluate multifaceted dietary and supplementation interventions in FEP; targeting-specific nutritional deficits and the range of aberrant biological processes implicated in the disorder.
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Affiliation(s)
- Joseph Firth
- NICM Health Research Institute, School of Science and Health, University of Western Sydney, Sydney, New South Wales, Australia.,Division of Psychology and Mental Health, University of Manchester, Manchester, UK
| | - Simon Rosenbaum
- School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.,Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia
| | - Philip B Ward
- School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.,Schizophrenia Research Unit, Ingham Institute of Applied Medical Research, Liverpool, New South Wales, Australia
| | - Jackie Curtis
- School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.,District Mental Health, South Eastern Sydney Local Health District, New South Wales, Australia
| | - Scott B Teasdale
- School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.,District Mental Health, South Eastern Sydney Local Health District, New South Wales, Australia
| | - Alison R Yung
- Division of Psychology and Mental Health, University of Manchester, Manchester, UK.,Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK
| | - Jerome Sarris
- NICM Health Research Institute, School of Science and Health, University of Western Sydney, Sydney, New South Wales, Australia.,Department of Psychiatry, University of Melbourne, The Melbourne Clinic, Melbourne, Victoria, Australia
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Banaschewski T, Belsham B, Bloch MH, Ferrin M, Johnson M, Kustow J, Robinson S, Zuddas A. Supplementation with polyunsaturated fatty acids (PUFAs) in the management of attention deficit hyperactivity disorder (ADHD). Nutr Health 2018; 24:279-284. [PMID: 29921155 PMCID: PMC6291899 DOI: 10.1177/0260106018772170] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
While pharmacotherapy and psychosocial interventions are recommended as the primary frontline treatment for attention deficit hyperactivity disorder (ADHD), alternative approaches to managing ADHD are becoming increasingly popular among patients and their families. Supplementation with polyunsaturated fatty acids (PUFAs) is an example of this. PUFA supplementation is not recommended by guidelines for managing ADHD; however, patients may still decide to use it. To provide direction to healthcare professionals (HCPs) managing ADHD, eight international experts in the field of adult and child ADHD came together for the Continuum Education Board: Omega Supplements in ADHD meeting. This commentary summarises the panel's consensus that current evidence suggests PUFA supplementation has a small beneficial effect on behaviour in children with ADHD, and that further high-quality research is needed to clearly evaluate and define its role in the management of ADHD of children, adolescents and adults. The panel concluded that in cases where patients use PUFA supplementation, HCPs should be comfortable explaining the potential gains that they may have and their possible side effects. The panel also concluded HCPs should not reinforce the idea that PUFA supplementation should replace treatment approaches with a more robust evidence base for managing ADHD.
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Affiliation(s)
- Tobias Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
| | | | - Michael H Bloch
- Child Study Center and Department of Psychiatry, Yale University, New Haven, USA
| | - Maite Ferrin
- Re:Cognition Health, London, UK
- University of Southampton, UK
| | - Mats Johnson
- Gillberg Neuropsychiatry Centre, Sahlgrenska Academy, Göteborg University, Sweden
| | - James Kustow
- Consultant Adult Psychiatrist and Adult ADHD specialist, London, UK
- UKAAN Executive board member and Chair of UKAAN’s Training Committee, London, UK
| | - Sarah Robinson
- PCM Scientific, London, UK
- Sarah Robinson, PCM Scientific, 140 London Wall, London, EC2Y 5DN, UK.
| | - Alessandro Zuddas
- Child and Adolescent Neuropsychiatry Unit, Department of Biomedical Science, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Italy
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Jordan W, Dobrowolny H, Bahn S, Bernstein HG, Brigadski T, Frodl T, Isermann B, Lessmann V, Pilz J, Rodenbeck A, Schiltz K, Schwedhelm E, Tumani H, Wiltfang J, Guest PC, Steiner J. Oxidative stress in drug-naïve first episode patients with schizophrenia and major depression: effects of disease acuity and potential confounders. Eur Arch Psychiatry Clin Neurosci 2018; 268:129-143. [PMID: 27913877 DOI: 10.1007/s00406-016-0749-7] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2016] [Accepted: 11/18/2016] [Indexed: 02/07/2023]
Abstract
Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43). Possible confounding factors were considered, and patients were followed-up after 6 weeks of treatment. No differences were observed regarding 8-OH-2-dG, MDA and GST. At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. However, 8-iso-PGF2α was associated with smoking, endocrine stress axis activation, C-reactive protein levels and low plasma concentrations of brain-derived neurotrophic factor. This study suggests a role of lipid peroxidation particularly in drug-naïve acutely ill schizophrenia patients and highlights the importance of taking into account other confounding factors in biomarker studies.
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Affiliation(s)
- Wolfgang Jordan
- Department of Psychiatry and Psychotherapy, Magdeburg Hospital GmbH, Magdeburg, Germany
- Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany
| | - Henrik Dobrowolny
- Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany
| | - Sabine Bahn
- Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK
| | - Hans-Gert Bernstein
- Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany
| | - Tanja Brigadski
- Institute of Physiology, University of Magdeburg, Magdeburg, Germany
- Center for Behavioral Brain Sciences, Magdeburg, Germany
| | - Thomas Frodl
- Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany
- Center for Behavioral Brain Sciences, Magdeburg, Germany
| | - Berend Isermann
- Institute of Clinical Chemistry and Pathobiochemistry, University of Magdeburg, Magdeburg, Germany
| | - Volkmar Lessmann
- Institute of Physiology, University of Magdeburg, Magdeburg, Germany
- Center for Behavioral Brain Sciences, Magdeburg, Germany
| | - Jürgen Pilz
- Laboratory of Stress Monitoring, Hardegsen, Germany
| | - Andrea Rodenbeck
- Sleep Laboratory, Department of Pneumology, Evangelisches Krankenhaus Goettingen-Weende gGmbH, Goettingen, Germany
- Department of Sleep Medicine and Clinical Chronobiology, Institute of Physiology, St. Hedwig Hospital, Charite, University of Berlin, Berlin, Germany
| | - Kolja Schiltz
- Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany
- Center for Behavioral Brain Sciences, Magdeburg, Germany
| | - Edzard Schwedhelm
- Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Hayrettin Tumani
- Department of Neurology, University of Ulm, Ulm, Germany
- Fachklinik für Neurologie Dietenbronn, Schwendi, Germany
| | - Jens Wiltfang
- Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany
- German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany
| | - Paul C Guest
- Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Johann Steiner
- Department of Psychiatry and Psychotherapy, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
- Center for Behavioral Brain Sciences, Magdeburg, Germany.
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Hoenders HR, Bartels-Velthuis AA, Vollbehr NK, Bruggeman R, Knegtering H, de Jong JT. Natural Medicines for Psychotic Disorders: A Systematic Review. J Nerv Ment Dis 2018; 206:81-101. [PMID: 29373456 PMCID: PMC5794244 DOI: 10.1097/nmd.0000000000000782] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Patients with psychotic disorders regularly use natural medicines, although it is unclear whether these are effective and safe. The aim of this study was to provide an overview of evidence for improved outcomes by natural medicines. A systematic literature search was performed through Medline, PsycINFO, CINAHL, and Cochrane until May 2015. In 110 randomized controlled trials, evidence was found for glycine, sarcosine, N-acetylcysteine, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol, and vitamin B6 to improve psychotic symptoms when added to antipsychotics. Ginkgo biloba and vitamin B6 seemed to reduce tardive dyskinesia and akathisia. Results on other compounds were negative or inconclusive. All natural agents, except reserpine, were well tolerated. Most study samples were small, study periods were generally short, and most results need replication. However, there is some evidence for beneficial effects of certain natural medicines.
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Affiliation(s)
- H.J. Rogier Hoenders
- *Lentis, Center for Integrative Psychiatry; †University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center; ‡Lentis Mental Health Institution; §University of Groningen, University Medical Center Groningen, Neuroimaging Center; ∥University of Amsterdam, Amsterdam, the Netherlands; and ¶Boston School of Medicine, Boston, Massachusetts
| | - Agna A. Bartels-Velthuis
- *Lentis, Center for Integrative Psychiatry; †University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center; ‡Lentis Mental Health Institution; §University of Groningen, University Medical Center Groningen, Neuroimaging Center; ∥University of Amsterdam, Amsterdam, the Netherlands; and ¶Boston School of Medicine, Boston, Massachusetts
| | - Nina K. Vollbehr
- *Lentis, Center for Integrative Psychiatry; †University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center; ‡Lentis Mental Health Institution; §University of Groningen, University Medical Center Groningen, Neuroimaging Center; ∥University of Amsterdam, Amsterdam, the Netherlands; and ¶Boston School of Medicine, Boston, Massachusetts
| | - Richard Bruggeman
- *Lentis, Center for Integrative Psychiatry; †University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center; ‡Lentis Mental Health Institution; §University of Groningen, University Medical Center Groningen, Neuroimaging Center; ∥University of Amsterdam, Amsterdam, the Netherlands; and ¶Boston School of Medicine, Boston, Massachusetts
| | - Henderikus Knegtering
- *Lentis, Center for Integrative Psychiatry; †University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center; ‡Lentis Mental Health Institution; §University of Groningen, University Medical Center Groningen, Neuroimaging Center; ∥University of Amsterdam, Amsterdam, the Netherlands; and ¶Boston School of Medicine, Boston, Massachusetts
| | - Joop T.V.M. de Jong
- *Lentis, Center for Integrative Psychiatry; †University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research Center; ‡Lentis Mental Health Institution; §University of Groningen, University Medical Center Groningen, Neuroimaging Center; ∥University of Amsterdam, Amsterdam, the Netherlands; and ¶Boston School of Medicine, Boston, Massachusetts
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Healy-Stoffel M, Levant B. N-3 (Omega-3) Fatty Acids: Effects on Brain Dopamine Systems and Potential Role in the Etiology and Treatment of Neuropsychiatric Disorders. CNS & NEUROLOGICAL DISORDERS DRUG TARGETS 2018; 17:216-232. [PMID: 29651972 PMCID: PMC6563911 DOI: 10.2174/1871527317666180412153612] [Citation(s) in RCA: 82] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 11/01/2017] [Accepted: 02/08/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & OBJECTIVE A number of neuropsychiatric disorders, including Parkinson's disease, schizophrenia, attention deficit hyperactivity disorder, and, to some extent, depression, involve dysregulation of the brain dopamine systems. The etiology of these diseases is multifactorial, involving genetic and environmental factors. Evidence suggests that inadequate levels of n-3 (omega- 3) polyunsaturated fatty acids (PUFA) in the brain may represent a risk factor for these disorders. These fatty acids, which are derived from the diet, are a major component of neuronal membranes and are of particular importance in brain development and function. Low levels of n-3 PUFAs in the brain affect the brain dopamine systems and, when combined with appropriate genetic and other factors, increase the risk of developing these disorders and/or the severity of the disease. This article reviews the neurobiology of n-3 PUFAs and their effects on dopaminergic function. CONCLUSION Clinical studies supporting their role in the etiologies of diseases involving the brain dopamine systems and the potential of n-3 PUFAs in the treatment of these disorders are discussed.
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Affiliation(s)
| | - Beth Levant
- Department of Pharmacology, Toxicology, and Therapeutics and the Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS, USA
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Agostoni C, Nobile M, Ciappolino V, Delvecchio G, Tesei A, Turolo S, Crippa A, Mazzocchi A, Altamura CA, Brambilla P. The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD. Int J Mol Sci 2017; 18:E2608. [PMID: 29207548 PMCID: PMC5751211 DOI: 10.3390/ijms18122608] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 11/24/2017] [Accepted: 11/27/2017] [Indexed: 12/24/2022] Open
Abstract
In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs) in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.
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Affiliation(s)
- Carlo Agostoni
- Pediatric Intermediate Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
- SIGENP (Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition), via Libero Temolo 4 (Torre U8), 20126 Milan, Italy.
| | - Maria Nobile
- Child Psychopathology Unit, Scientific Institute, IRCCS Eugenio Medea, via Don Luigi Monza 20, Bosisio Parini, 23842 Lecco, Italy.
| | - Valentina Ciappolino
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
| | - Giuseppe Delvecchio
- Department of Pathophysiology and Transplantation, Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
| | - Alessandra Tesei
- Child Psychopathology Unit, Scientific Institute, IRCCS Eugenio Medea, via Don Luigi Monza 20, Bosisio Parini, 23842 Lecco, Italy.
| | - Stefano Turolo
- Pediatric Nephrology & Dialysis, Milano Fondazione IRCCS Cà Grande Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
| | - Alessandro Crippa
- Child Psychopathology Unit, Scientific Institute, IRCCS Eugenio Medea, via Don Luigi Monza 20, Bosisio Parini, 23842 Lecco, Italy.
| | - Alessandra Mazzocchi
- Pediatric Intermediate Care Unit, Department of Clinical Sciences and Community Health, Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
| | - Carlo A Altamura
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
| | - Paolo Brambilla
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ospedale Cà Granda-Ospedale Maggiore Policlinico, University of Milan, 20122 Milan, Italy.
- Department of Psychiatry and Behavioural Neurosciences, University of Texas at Houston, Houston, 77021 TX, USA.
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Ghosh S, Dyer RA, Beasley CL. Evidence for altered cell membrane lipid composition in postmortem prefrontal white matter in bipolar disorder and schizophrenia. J Psychiatr Res 2017; 95:135-142. [PMID: 28843843 DOI: 10.1016/j.jpsychires.2017.08.009] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Revised: 07/24/2017] [Accepted: 08/09/2017] [Indexed: 11/30/2022]
Abstract
Brain imaging suggests that white matter abnormalities, including compromised white matter integrity in the frontal lobe, are shared across bipolar disorder (BD) and schizophrenia (SCZ). However, the precise molecular and cellular correlates remain to be elucidated. Given evidence for widespread alterations in cell membrane lipid composition in both disorders, we sought to investigate whether lipid composition is disturbed in frontal white matter in SCZ and BD. The phospholipids phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were quantified in white matter adjacent to the dorsolateral prefrontal cortex in subjects with BD (n = 34), SCZ (n = 35), and non-psychiatric controls (n = 35) using high-pressure liquid chromatography. Individual fatty acid species and plasmalogens were then quantified separately in PE and PC fractions by gas liquid chromatography. PC was significantly lower in the BD group, compared to controls. The fatty acids PE22:0, PE24:1 and PE20:2n6 were higher, and PC20:4n6, PE22:5n6 and PC22:5n6 lower in the BD group, relative to the control group. PE22:1 was higher and PC20:3n6, PE22:5n6 and PC22:5n6 lower in the SCZ group, compared to the control group. These data provide evidence for altered lipid composition in white matter in both BD and SCZ. Changes in white matter lipid composition could ultimately contribute to dysfunction of frontal white matter circuits in SCZ and BD.
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Affiliation(s)
- Sanjoy Ghosh
- Department of Biology, Irving K. Barber School of Arts & Sciences, University of British Columbia-Okanagan, Kelowna, British Columbia, Canada
| | - Roger A Dyer
- Nutrition and Metabolism Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Clare L Beasley
- Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
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34
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Mitra S, Natarajan R, Ziedonis D, Fan X. Antioxidant and anti-inflammatory nutrient status, supplementation, and mechanisms in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2017; 78:1-11. [PMID: 28499901 DOI: 10.1016/j.pnpbp.2017.05.005] [Citation(s) in RCA: 56] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 05/06/2017] [Accepted: 05/08/2017] [Indexed: 10/19/2022]
Abstract
Over 50 million people around the world suffer from schizophrenia, a severe mental illness characterized by misinterpretation of reality. Although the exact causes of schizophrenia are still unknown, studies have indicated that inflammation and oxidative stress may play an important role in the etiology of the disease. Pro-inflammatory cytokines are crucial for normal central nervous development and proper functioning of neural networks and neurotransmitters. Patients with schizophrenia tend to have abnormal immune activation resulting in elevated pro-inflammatory cytokine levels, ultimately leading to functional brain impairments. Patients with schizophrenia have also been found to suffer from oxidative stress, a result of an imbalance between the production of free radicals and the ability to detoxify their harmful effects. Furthermore, inflammation and oxidative stress are implicated to be related to the severity of psychotic symptoms. Several nutrients are known to have anti-inflammatory and antioxidant functions through various mechanisms in our body. The present review evaluates studies and literature that address the status and supplementation of omega-3 polyunsaturated fatty acids, vitamin D, B vitamins (B6, folate, B12), vitamin E, and carotenoids in different stages of schizophrenia. The possible anti-inflammatory and antioxidant mechanisms of action of each nutrient are discussed.
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Affiliation(s)
- Sumedha Mitra
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA
| | - Radhika Natarajan
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA
| | - Douglas Ziedonis
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA
| | - Xiaoduo Fan
- Department of Psychiatry, UMass Memorial Medical Center/University of Massachusetts Medical School, One Biotech, 365 Plantation Street, Worcester, MA 01605, USA.
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Firth J, Stubbs B, Sarris J, Rosenbaum S, Teasdale S, Berk M, Yung AR. The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis. Psychol Med 2017; 47:1515-1527. [PMID: 28202095 DOI: 10.1017/s0033291717000022] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. METHOD We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. RESULTS An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01-1.01, p = 0.047, I 2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00-1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. CONCLUSIONS There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.
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Affiliation(s)
- J Firth
- Division of Psychology and Mental Health,University of Manchester,Manchester,UK
| | - B Stubbs
- Physiotherapy Department,South London and Maudsley NHS Foundation Trust, London,UK
| | - J Sarris
- Department of Psychiatry,University of Melbourne, The Melbourne Clinic,Melbourne,Australia
| | - S Rosenbaum
- Department of Exercise Physiology,School of Medical Sciences,Faculty of Medicine,University of New South Wales,Sydney,Australia
| | - S Teasdale
- Keeping the Body in Mind Program,South Eastern Sydney Local Health District,Sydney,Australia
| | - M Berk
- Deakin University, IMPACT Strategic Research Centre, School of Medicine,Victoria,Australia
| | - A R Yung
- Division of Psychology and Mental Health,University of Manchester,Manchester,UK
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Melbourne JK, Feiner B, Rosen C, Sharma RP. Targeting the Immune System with Pharmacotherapy in Schizophrenia. CURRENT TREATMENT OPTIONS IN PSYCHIATRY 2017; 4:139-151. [PMID: 28674674 PMCID: PMC5493152 DOI: 10.1007/s40501-017-0114-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Jennifer K. Melbourne
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL, USA, 60612
| | - Benjamin Feiner
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL, USA, 60612
| | - Cherise Rosen
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL, USA, 60612
| | - Rajiv P. Sharma
- The Psychiatric Institute, University of Illinois at Chicago, 1601 W. Taylor St., Chicago, IL, USA, 60612
- Jesse Brown Veterans Affairs Medical Center, 820 South Damen Avenue (M/C 151), Chicago, IL, USA, 60612
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Pawełczyk T, Grancow-Grabka M, Trafalska E, Szemraj J, Pawełczyk A. Oxidative stress reduction related to the efficacy of n-3 polyunsaturated fatty acids in first episode schizophrenia: Secondary outcome analysis of the OFFER randomized trial. Prostaglandins Leukot Essent Fatty Acids 2017; 121:7-13. [PMID: 28651701 DOI: 10.1016/j.plefa.2017.05.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 01/10/2017] [Accepted: 05/25/2017] [Indexed: 02/08/2023]
Abstract
Intervention studies of n-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia have not examined changes in oxidative stress. A randomized placebo-controlled trial of a 26-week intervention composed of 2.2g/day of n-3 PUFA was found to reduce symptom severity in first-episode schizophrenia patients. The present study is an extension of our previous report, whose secondary aim was to assess the association between the clinical effect of n-3 PUFA and changes in oxidative stress indices. Seventy-one patients aged 16-35 were enrolled in the study and randomly assigned to the study arms. Total plasma antioxidant capacity and 8-epi-isoprostane F2α content were assessed at baseline and at weeks 8 and 26 of the study as secondary outcome measures. Significant changes in oxidative stress indices favouring the intervention group were observed: decreases in 8-isoprostane F2α (p<0.001) and increases in total plasma antioxidant capacity (p<0.001). Significant correlations between changes in clinical scores relevant to symptom severity and changes in oxidative indices were observed. The results of the present study hence suggest that the efficacy of a six-month intervention with n-3 PUFA observed in first-episode schizophrenia may be related to improvement in oxidative stress indices.
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Affiliation(s)
- T Pawełczyk
- Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216 Lodz, Poland.
| | - M Grancow-Grabka
- Child and Adolescent Psychiatry Unit, Central Teaching Hospital, Medical University of Lodz, ul. Pomorska 251, 92-213 Lodz, Poland.
| | - E Trafalska
- Department of Nutrition Hygiene and Epidemiology, Medical University of Lodz, ul. Jaracza 63, 90-251 Lodz, Poland.
| | - J Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, ul. Mazowiecka 6/8, 92-215 Lodz, Poland.
| | - A Pawełczyk
- Department of Affective and Psychotic Disorders, Medical University of Lodz, ul. Czechoslowacka 8/10, 92-216 Lodz, Poland.
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38
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Lipids in psychiatric disorders and preventive medicine. Neurosci Biobehav Rev 2017; 76:336-362. [DOI: 10.1016/j.neubiorev.2016.06.002] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 05/06/2016] [Accepted: 06/06/2016] [Indexed: 01/12/2023]
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Bentsen H. Dietary polyunsaturated fatty acids, brain function and mental health. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2017. [PMCID: PMC5445635 DOI: 10.1080/16512235.2017.1281916] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 10/30/2022]
Abstract
The importance of dietary polyunsaturated fatty acids for our health and our economy is immense. The present paper is a quick guide to this topic, which is highly complex and full of conflicts. One aspect is highlighted, namely the relationship between these substances and our mental health. Relevant chemical and physical properties of polyunsaturated fatty acids are briefly presented. The questions of needs and supplies are discussed. The effects of these fatty acids on the human body, in particular the brain, are described. How do they influence mental health? The most recent meta-analyses and systematic reviews have been used as sources, and outstanding references have been selected. We want to convey updated knowledge, based on good science, for better decision making in preventive and therapeutic health care, as well as in agriculture, fishery and food industries.
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Affiliation(s)
- Håvard Bentsen
- Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway
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40
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Barnes TRE, Leeson VC, Paton C, Costelloe C, Simon J, Kiss N, Osborn D, Killaspy H, Craig TKJ, Lewis S, Keown P, Ismail S, Crawford M, Baldwin D, Lewis G, Geddes J, Kumar M, Pathak R, Taylor S. Antidepressant Controlled Trial For Negative Symptoms In Schizophrenia (ACTIONS): a double-blind, placebo-controlled, randomised clinical trial. Health Technol Assess 2017; 20:1-46. [PMID: 27094189 DOI: 10.3310/hta20290] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Negative symptoms of schizophrenia represent deficiencies in emotional responsiveness, motivation, socialisation, speech and movement. When persistent, they are held to account for much of the poor functional outcomes associated with schizophrenia. There are currently no approved pharmacological treatments. While the available evidence suggests that a combination of antipsychotic and antidepressant medication may be effective in treating negative symptoms, it is too limited to allow any firm conclusions. OBJECTIVE To establish the clinical effectiveness and cost-effectiveness of augmentation of antipsychotic medication with the antidepressant citalopram for the management of negative symptoms in schizophrenia. DESIGN A multicentre, double-blind, individually randomised, placebo-controlled trial with 12-month follow-up. SETTING Adult psychiatric services, treating people with schizophrenia. PARTICIPANTS Inpatients or outpatients with schizophrenia, on continuing, stable antipsychotic medication, with persistent negative symptoms at a criterion level of severity. INTERVENTIONS Eligible participants were randomised 1 : 1 to treatment with either placebo (one capsule) or 20 mg of citalopram per day for 48 weeks, with the clinical option at 4 weeks to increase the daily dosage to 40 mg of citalopram or two placebo capsules for the remainder of the study. MAIN OUTCOME MEASURES The primary outcomes were quality of life measured at 12 and 48 weeks assessed using the Heinrich's Quality of Life Scale, and negative symptoms at 12 weeks measured on the negative symptom subscale of the Positive and Negative Syndrome Scale. RESULTS No therapeutic benefit in terms of improvement in quality of life or negative symptoms was detected for citalopram over 12 weeks or at 48 weeks, but secondary analysis suggested modest improvement in the negative symptom domain, avolition/amotivation, at 12 weeks (mean difference -1.3, 95% confidence interval -2.5 to -0.09). There were no statistically significant differences between the two treatment arms over 48-week follow-up in either the health economics outcomes or costs, and no differences in the frequency or severity of adverse effects, including corrected QT interval prolongation. LIMITATIONS The trial under-recruited, partly because cardiac safety concerns about citalopram were raised, with the 62 participants recruited falling well short of the target recruitment of 358. Although this was the largest sample randomised to citalopram in a randomised controlled trial of antidepressant augmentation for negative symptoms of schizophrenia and had the longest follow-up, the power of statistical analysis to detect significant differences between the active and placebo groups was limited. CONCLUSION Although adjunctive citalopram did not improve negative symptoms overall, there was evidence of some positive effect on avolition/amotivation, recognised as a critical barrier to psychosocial rehabilitation and achieving better social and community functional outcomes. Comprehensive assessment of side-effect burden did not identify any serious safety or tolerability issues. The addition of citalopram as a long-term prescribing strategy for the treatment of negative symptoms may merit further investigation in larger studies. FUTURE WORK Further studies of the viability of adjunctive antidepressant treatment for negative symptoms in schizophrenia should include appropriate safety monitoring and use rating scales that allow for evaluation of avolition/amotivation as a discrete negative symptom domain. Overcoming the barriers to recruiting an adequate sample size will remain a challenge. TRIAL REGISTRATION European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2009-009235-30 and Current Controlled Trials ISRCTN42305247. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 29. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Thomas R E Barnes
- Centre for Mental Health, Imperial College London, London, UK.,West London Mental Health NHS Trust, London, UK
| | - Verity C Leeson
- Centre for Mental Health, Imperial College London, London, UK
| | - Carol Paton
- Centre for Mental Health, Imperial College London, London, UK.,Oxleas NHS Foundation Trust, Dartford, UK
| | - Céire Costelloe
- National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, London, UK
| | - Judit Simon
- Department of Health Economics, Centre for Public Health, Medical University of Vienna, Vienna, Austria
| | - Noemi Kiss
- Department of Health Economics, Centre for Public Health, Medical University of Vienna, Vienna, Austria
| | - David Osborn
- Division of Psychiatry, University College London, UK.,Camden and Islington NHS Foundation Trust, London, UK
| | - Helen Killaspy
- Division of Psychiatry, University College London, UK.,Camden and Islington NHS Foundation Trust, London, UK
| | - Tom K J Craig
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Shôn Lewis
- Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK
| | - Patrick Keown
- Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Shajahan Ismail
- Sheffield Health and Social Care NHS Foundation Trust, Sheffield, UK
| | - Mike Crawford
- Centre for Mental Health, Imperial College London, London, UK
| | - David Baldwin
- Mental Health Group, University of Southampton Faculty of Medicine, Southampton, UK
| | - Glyn Lewis
- Division of Psychiatry, University College London, UK.,Camden and Islington NHS Foundation Trust, London, UK
| | - John Geddes
- Department of Psychiatry, University of Oxford, Oxford, UK
| | - Manoj Kumar
- South Staffordshire and Shropshire Healthcare NHS Foundation Trust, Stafford, UK
| | - Rudresh Pathak
- Lincolnshire Partnership NHS Foundation Trust, Lincoln, UK
| | - Simon Taylor
- Derbyshire Healthcare NHS Foundation Trust, Derby, UK
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Abstract
Abstract
Ω-3 unsaturated fatty acids are compounds belonging to the group of essential fatty acids (EFAs). The history of the discovery of EFAs dates back to the 1930s of the twentieth century, however, growing interest in ω-3 EFAs in the context of mental health has been observed since the year 2000. In view of their multidirectional action, these compounds are a promising form of adjunctive therapy of many illnesses, including psychiatric disorders. The present article aims to review the literature on the clinical applicability of ω-3 EFAs in treating schizophrenia. We present the results of preclinical studies in this area and the mechanisms of ω-3 EFAs action discussed by the authors. The randomized controlled trials (RCTs) evaluating the possibility of using ω-3 EFAs in schizophrenia are characterized in detail. The results of the tests are not clear, which may result from the methodological diversity of interventions made. Ω-3 EFAs seem to be a promising form of adjunctive therapy of schizophrenia. Further research is needed, which will allow for defining groups of patients in which intervention will bring the expected results.
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Koga M, Serritella AV, Sawa A, Sedlak TW. Implications for reactive oxygen species in schizophrenia pathogenesis. Schizophr Res 2016; 176:52-71. [PMID: 26589391 DOI: 10.1016/j.schres.2015.06.022] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2014] [Revised: 06/20/2015] [Accepted: 06/23/2015] [Indexed: 12/18/2022]
Abstract
Oxidative stress is a well-recognized participant in the pathophysiology of multiple brain disorders, particularly neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. While not a dementia, a wide body of evidence has also been accumulating for aberrant reactive oxygen species and inflammation in schizophrenia. Here we highlight roles for oxidative stress as a common mechanism by which varied genetic and epidemiologic risk factors impact upon neurodevelopmental processes that underlie the schizophrenia syndrome. While there is longstanding evidence that schizophrenia may not have a single causative lesion, a common pathway involving oxidative stress opens the possibility for intervention at susceptible phases.
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Affiliation(s)
- Minori Koga
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 3-166, Baltimore, MD 21287, USA
| | - Anthony V Serritella
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 3-166, Baltimore, MD 21287, USA
| | - Akira Sawa
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 3-166, Baltimore, MD 21287, USA
| | - Thomas W Sedlak
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Meyer 3-166, Baltimore, MD 21287, USA.
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Vijayakumar N, Bartholomeusz C, Whitford T, Hermens DF, Nelson B, Rice S, Whittle S, Pantelis C, McGorry P, Schäfer MR, Amminger GP. White matter integrity in individuals at ultra-high risk for psychosis: a systematic review and discussion of the role of polyunsaturated fatty acids. BMC Psychiatry 2016; 16:287. [PMID: 27515430 PMCID: PMC4982267 DOI: 10.1186/s12888-016-0932-4] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2015] [Accepted: 06/15/2016] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Schizophrenia is thought to be a neurodevelopmental disorder with pathophysiological processes beginning in the brain prior to the emergence of clinical symptoms. Recent evidence from neuroimaging studies using techniques such as diffusion tensor imaging has identified white matter abnormalities that are suggestive of disrupted brain myelination and neuronal connectivity. Identifying whether such effects exist in individuals at high risk for developing psychosis may help with prevention and early intervention strategies. In addition, there is preliminary evidence for a role of lipid biology in the onset of psychosis, along with well-established evidence of its role in myelination of white matter tracts. As such, this article synthesises the literature on polyunsaturated fatty acids (PUFAs) in myelination and schizophrenia, hypothesizing that white matter abnormalities may potentially mediate the relationship between PUFAs and schizophrenia. METHODS Diffusion tensor imaging studies were identified through a systematic search of existing literature. Studies examined white matter integrity in ultra-high risk (UHR) samples, as assessed using structured diagnostic interviews. Data was extracted and summarised as a narrative review. RESULTS Twelve studies met inclusion criteria, and findings identified reduced fractional anisotropy and higher diffusivity. Although the exact location of abnormalities remains uncertain, fronto-temporal and fronto-limbic connections, including the superior longitudinal and uncinate fasiculus, cingulum, and corpus callosum appear to be implicated. Because of preliminary evidence suggesting lipid biology may be relevant for the onset of psychosis, a discussion is provided of the role of polyunsaturated fatty acids (PUFAs) in myelination and risk for psychosis. CONCLUSIONS While the function of PUFAs in myelination is well-established, there is growing evidence of reduced PUFA concentration in UHR samples, highlighting the need for research to examine the relationship between PUFA and white matter integrity in high-risk samples and age-matched healthy controls. Such investigations will help to better understand the pathophysiology of the disorder, and potentially assist in the development of novel treatment and early intervention strategies.
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Affiliation(s)
- Nandita Vijayakumar
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
- Department of Psychology, University of Oregon, Eugene, USA
| | - Cali Bartholomeusz
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
| | - Thomas Whitford
- Brain & Mind Research Institute, Central Clinical School, University of Sydney, Sydney, Australia
| | | | - Barnaby Nelson
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
| | - Simon Rice
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
| | - Sarah Whittle
- Melbourne Neuropsychiatry Centre, The University of Melbourne, Melbourne, Australia
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, The University of Melbourne, Melbourne, Australia
| | - Patrick McGorry
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
| | - Miriam R. Schäfer
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
| | - G. Paul Amminger
- Orygen, The National Centre of Excellence in Youth Mental Health, The University of Melbourne, 35 Poplar Road, Parkville, Victoria 3052 Australia
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Berger G. Comments on Bozzatello et al. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data. J. Clin. Med. 2016, 5, 67. J Clin Med 2016; 5:jcm5080069. [PMID: 27527228 PMCID: PMC4999789 DOI: 10.3390/jcm5080069] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 07/28/2016] [Indexed: 12/31/2022] Open
Affiliation(s)
- Gregor Berger
- Department of Child and Adolescent Psychiatry and Psychotherapy, Outpatient Clinics and Specialized Care, Emergency Services, University Hospital of Psychiatry Zurich, Neumünsterallee 3, P.O. Box 1482, 8032 Zurich, Switzerland.
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Bozzatello P, Brignolo E, De Grandi E, Bellino S. Supplementation with Omega-3 Fatty Acids in Psychiatric Disorders: A Review of Literature Data. J Clin Med 2016; 5:E67. [PMID: 27472373 PMCID: PMC4999787 DOI: 10.3390/jcm5080067] [Citation(s) in RCA: 106] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 05/18/2016] [Accepted: 06/13/2016] [Indexed: 11/16/2022] Open
Abstract
A new application for omega-3 fatty acids has recently emerged, concerning the treatment of several mental disorders. This indication is supported by data of neurobiological research, as highly unsaturated fatty acids (HUFAs) are highly concentrated in neural phospholipids and are important components of the neuronal cell membrane. They modulate the mechanisms of brain cell signaling, including the dopaminergic and serotonergic pathways. The aim of this review is to provide a complete and updated account of the empirical evidence of the efficacy and safety that are currently available for omega-3 fatty acids in the treatment of psychiatric disorders. The main evidence for the effectiveness of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been obtained in mood disorders, in particular in the treatment of depressive symptoms in unipolar and bipolar depression. There is some evidence to support the use of omega-3 fatty acids in the treatment of conditions characterized by a high level of impulsivity and aggression and borderline personality disorders. In patients with attention deficit hyperactivity disorder, small-to-modest effects of omega-3 HUFAs have been found. The most promising results have been reported by studies using high doses of EPA or the association of omega-3 and omega-6 fatty acids. In schizophrenia, current data are not conclusive and do not allow us either to refuse or support the indication of omega-3 fatty acids. For the remaining psychiatric disturbances, including autism spectrum disorders, anxiety disorders, obsessive-compulsive disorder, eating disorders and substance use disorder, the data are too scarce to draw any conclusion. Concerning tolerability, several studies concluded that omega-3 can be considered safe and well tolerated at doses up to 5 g/day.
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Affiliation(s)
- Paola Bozzatello
- Centre for Personality Disorders, Department of Neuroscience, University of Turin, 10126 Turin, Italy.
| | - Elena Brignolo
- Centre for Personality Disorders, Department of Neuroscience, University of Turin, 10126 Turin, Italy.
| | - Elisa De Grandi
- Centre for Personality Disorders, Department of Neuroscience, University of Turin, 10126 Turin, Italy.
| | - Silvio Bellino
- Centre for Personality Disorders, Department of Neuroscience, University of Turin, 10126 Turin, Italy.
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Knöchel C, Voss M, Grüter F, Alves GS, Matura S, Sepanski B, Stäblein M, Wenzler S, Prvulovic D, Carvalho AF, Oertel-Knöchel V. Omega 3 Fatty Acids: Novel Neurotherapeutic Targets for Cognitive Dysfunction in Mood Disorders and Schizophrenia? Curr Neuropharmacol 2016; 13:663-80. [PMID: 26467414 PMCID: PMC4761636 DOI: 10.2174/1570159x13666150630173047] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Revised: 02/25/2015] [Accepted: 02/27/2015] [Indexed: 01/23/2023] Open
Abstract
An increasing body of evidences from preclinical as well as epidemiological and clinical
studies suggest a potential beneficial role of dietary intake of omega-3 fatty acids for cognitive functioning.
In this narrative review, we will summarize and discuss recent findings from epidemiological, interventional
and experimental studies linking dietary consumption of omega-3 fatty acids to cognitive
function in healthy adults. Furthermore, affective disorders and schizophrenia (SZ) are characterized
by cognitive dysfunction encompassing several domains. Cognitive dysfunction is closely related to impaired functioning
and quality of life across these conditions. Therefore, the current review focues on the potential influence of omega-3 fatty
acids on cognition in SZ and affective disorders. In sum, current data predominantly from mechanistic models and animal
studies suggest that adjunctive omega-3 fatty acid supplementation could lead to improved cognitive functioning in SZ
and affective disorders. However, besides its translational promise, evidence for clinical benefits in humans has been
mixed. Notwithstanding evidences indicate that adjunctive omega-3 fatty acids may have benefit for affective symptoms
in both unipolar and bipolar depression, to date no randomized controlled trial had evaluated omega-3 as cognitive
enhancer for mood disorders, while a single published controlled trial suggested no therapeutic benefit for cognitive
improvement in SZ. Considering the pleiotropic mechanisms of action of omega-3 fatty acids, the design of well-designed
controlled trials of omega-3 supplementation as a novel, domain-specific, target for cognitive impairment in SZ and
affective disorders is warranted.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Viola Oertel-Knöchel
- Laboratory for Neuroimaging, Dept. of Psychiatry, Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy; Heinrich-Hoffmann-Str. 10, Goethe-University, 60528 Frankfurt
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El-Sayed El-Sisi A, Sokkar SS, El-Sayed El-Sayad M, Sayed Ramadan E, Osman EY. Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia. Biomed Pharmacother 2016; 82:425-31. [PMID: 27470381 DOI: 10.1016/j.biopha.2016.05.024] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 05/16/2016] [Accepted: 05/16/2016] [Indexed: 01/25/2023] Open
Abstract
The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib+risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib+risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib+risperidone, omega-3+risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib+risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.
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Affiliation(s)
- Alaa El-Sayed El-Sisi
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt
| | - Samia Salem Sokkar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt
| | | | - Ehab Sayed Ramadan
- Department of Neuropsychiatry, Faculty of Medicine, University of Tanta, Egypt
| | - Enass Yossef Osman
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt.
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Karlsgodt KH. Diffusion Imaging of White Matter In Schizophrenia: Progress and Future Directions. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2016; 1:209-217. [PMID: 27453952 PMCID: PMC4955654 DOI: 10.1016/j.bpsc.2015.12.001] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Diffusion tensor imaging (DTI) is a powerful tool for the in-vivo assessment of white matter microstructure. The application of DTI methodologies to the study of schizophrenia has supported and advanced the hypothesis of schizophrenia as a disorder of disrupted connectivity. In the context of impaired structural connectivity, the extended time frame of white matter development may offer unique opportunities for treatment that can capitalize on the neural flexibility that is still present in the period leading up to and after disease onset. Therefore, it is important to gain a clear understanding of white matter deficits and how they may emerge and change across the illness. However, while there is broad consistency in the findings of white matter deficits in patients with schizophrenia, there is also a great deal of variability in specific findings across studies. In this review, the aim is to move beyond summarizing case-control analyses, to consider the many factors that may impact DTI measures, to explain variability of findings, and to explore future directions for the field. The topics explored include ways to parse DTI patterns associated with different disease subtypes, ways in which novel and established treatments might interact with or enhance white matter, ways of dissociating developmental change from the disease process itself, and understanding the role of emerging analytic methodologies.
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Affiliation(s)
- Katherine H Karlsgodt
- Psychiatry Research Division, Zucker Hillside Hospital and Feinstein Institute for Medical Research; Department of Psychiatry, Hofstra NorthShore LIJ School of Medicine
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Hamazaki K, Maekawa M, Toyota T, Iwayama Y, Dean B, Hamazaki T, Yoshikawa T. Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: A case-control study. Schizophr Res 2016; 171:225-32. [PMID: 26792082 DOI: 10.1016/j.schres.2016.01.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 12/17/2015] [Accepted: 01/05/2016] [Indexed: 11/26/2022]
Abstract
BACKGROUND Abnormal levels of n-3 polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), have been found in the postmortem frontal cortex, particularly the orbitofrontal cortex, of patients with schizophrenia. Altered mRNA expression of fatty acid binding protein (FABP) 5 and FABP7 has likewise been reported. METHODS This study investigated whether PUFAs in the frontal cortex [Brodmann area (BA) 8] and mRNA expression of FABP3, 5, and 7 were different between patients with schizophrenia (n=95) and unaffected controls (n=93). RESULTS In contrast to previous studies, no significant differences were found in DHA between the groups. Although arachidonic acid (AA) levels were significantly decreased in the schizophrenia group, no association was found between AA and schizophrenia on logistic regression analysis. Only FABP3 expression was significantly lower in the schizophrenia group than in the control group. Significant inverse associations were seen between only two saturated fatty acids, behenic acid and lignoceric acid, and FABP3 expression. CONCLUSIONS We found no evidence that major PUFA levels in BA8 are involved in the etiology of schizophrenia. Although FABP3 expression was not correlated with any of the major PUFAs, it might play a novel role in the pathology of BA8 in a subset of patients with schizophrenia.
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Affiliation(s)
- Kei Hamazaki
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan; Department of Public Health, Faculty of Medicine, University of Toyama, Toyama City, Toyama 9300194, Japan.
| | - Motoko Maekawa
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan
| | - Tomoko Toyota
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan
| | - Yoshimi Iwayama
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan
| | - Brian Dean
- The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia
| | - Tomohito Hamazaki
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan
| | - Takeo Yoshikawa
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan
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A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia. J Psychiatr Res 2016; 73:34-44. [PMID: 26679763 DOI: 10.1016/j.jpsychires.2015.11.013] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 11/17/2015] [Accepted: 11/20/2015] [Indexed: 11/23/2022]
Abstract
Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16-35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients.
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