Article
Health Care Sciences & Services
Gesche Jurgens, Benjamin Skov Kaas-Hansen, Merete Nordentoft, Thomas Werge, Stig Ejdrup Andersen
Summary: This study found an association between genetically predicted CYP2D6 metabolic capacity and antipsychotic-induced weight gain. The results showed significant weight gain in both CYP2D6 poor metabolizers and ultrarapid metabolizers after taking antipsychotic drugs.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Behavioral Sciences
Mary Seeman
Summary: The review examines the potential role of intestinal organisms in response/non-response to antipsychotics, highlighting that current research in this area is mostly theoretical but showing increasing evidence from animal experiments and clinical trials on the impact of gut bacteria on drug response.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Review
Psychiatry
Kenn Lee, Seri Abraham, Robert Cleaver
Summary: This study evaluated the efficacy of licensed weight loss medications (WLMs) for treating antipsychotic-induced weight gain (AIWG) and obesity in schizophrenia and psychosis. The findings showed that liraglutide had the strongest evidence compared to other licensed WLMs in improving weight, BMI, waist circumference, HbA1c, cholesterol, and LDL readings. This evidence supports the use of liraglutide in treating AIWG and OSP.
GENERAL HOSPITAL PSYCHIATRY
(2022)
Article
Pharmacology & Pharmacy
Farhana Islam, Xiaoyu Men, Kazunari Yoshida, Clement C. Zai, Daniel J. Mueller
Summary: Pharmacogenetics research has shown that genetic factors influence the efficacy and tolerability of antipsychotic treatment, with the most robust findings related to associations between polymorphisms in CYP2D6 and exposure and response to specific antipsychotics. Product labels and guidelines have provided dosing recommendations based on CYP2D6 metabolizer phenotypes.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Zhenyu Zhu, Yuxiu Gu, Cuirong Zeng, Man Yang, Hao Yu, Hui Chen, Bikui Zhang, Hualin Cai
Summary: Long-term use of olanzapine may lead to lipid metabolic disorders. This study investigates the role of the gut microbiota-brain axis in olanzapine-induced lipid disturbances. The results show that olanzapine causes weight gain, increased adipose tissue ratio, and elevated triglyceride and cholesterol levels. Furthermore, olanzapine affects gut microbiota and their metabolites, as well as neuropeptide expression in the hypothalamus.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Psychology, Multidisciplinary
Luiza Grycuk, Francesca Moruzzi, Elena Bardjesteh, Fiona Gaughran, Iain C. Campbell, Ulrike Schmidt
Summary: The study provides insights into the perceptions and experiences of individuals with schizophrenia regarding transcranial direct current stimulation (tDCS). Participants were concerned about the safety of tDCS, but educational materials and a good relationship with the researcher helped alleviate their fears. Although participants found tDCS uncomfortable, they agreed that the unpleasant sensations were short-lived and did not cause long-term anxiety.
FRONTIERS IN PSYCHOLOGY
(2021)
Article
Psychiatry
Nini de Boer, Sinan Guloksuz, Caroline van Baal, Leonie Willebrands, Jeroen Deenik, Christiaan H. Vinkers, Inge Winter-van Rossum, Janneke Zinkstok, Ingeborg Wilting, Jasper B. Zantvoord, Frank Backx, Wilma E. Swildens, Marieke Schouw, Jan Bogers, Folkwin Hulshof, Rudolf de Knijff, Peter Duindam, Mike Veereschild, Maarten Bak, Geert Frederix, Lieuwe de Haan, Jim van Os, Wiepke Cahn, Jurjen J. Luykx
Summary: This study aims to evaluate the use of metformin for the treatment of antipsychotic-induced weight gain by comparing metformin with placebo in those receiving treatment as usual. The primary outcome measure is the difference in body weight between the two arms at 26 weeks compared to baseline.
Article
Psychiatry
Xinyu Fang, Chunying Gao, Weifeng Wu, Xiuxiu Hu, Miaomiao Shao, Chou Zhou, Renliang Cai, Jin Fang, Yi Li, Yue Xu, Xiangrong Zhang
Summary: This study explored the relationship between weight gain in schizophrenia patients with atypical antipsychotic treatment and gut microbiome. The results showed that there were no significant differences in alpha diversity between normal-weight and overweight schizophrenia patients treated with atypical antipsychotics. However, the beta diversity analysis revealed distinct clustering patterns for overweight and normal-weight patients. The composition of the gut microbiome also differed between the two groups. Function prediction identified several pathways that were significantly different between groups. Correlation analysis indicated associations between specific bacteria and BMI. Overall, these findings suggest that perturbations in the gut microbiome composition and functional pathways may contribute to weight gain in schizophrenia patients treated with atypical antipsychotics.
PSYCHIATRY RESEARCH
(2023)
Article
Psychiatry
Yi Su, Hao Yan, Liangkun Guo, Tianlan Lu, Dai Zhang, Weihua Yue
Summary: The study investigated the association between MTHFR C677T gene polymorphism and antipsychotic-induced weight gain and metabolic abnormalities in patients with schizophrenia. Results showed a significant link between MTHFR C677T and body weight mass index change after 6-week risperidone treatment, indicating a high risk of antipsychotic-induced weight gain and metabolism abnormalities in patients carrying the MTHFR C677 allele.
FRONTIERS IN PSYCHIATRY
(2021)
Article
Microbiology
Wei Pan, Jinxiu Zhao, Jiacheng Wu, Daxiang Xu, Xianran Meng, Pengfei Jiang, Hongli Shi, Xing Ge, Xiaoying Yang, Minmin Hu, Peng Zhang, Renxian Tang, Nathan Nagaratnam, Kuiyang Zheng, Xu-Feng Huang, Yinghua Yu
Summary: This study found that Dimethyl itaconate (DI) improves cognitive impairment caused by high-fat diet by improving the gut-brain axis, reducing intestinal inflammation, and improving gut microbiota. DI works by reducing synaptic damage and inflammation in the brain. In addition, DI improves gut barrier function and reduces inflammatory cell infiltration. By modulating the ratio of probiotics and promoting the restoration of gut microbiota, DI improves gut microbiota dysbiosis. These results suggest that DI has potential as a therapeutic drug for improving cognitive impairment.
Review
Cell Biology
Qinwen Wang, Qianyue Yang, Xingyin Liu
Summary: The gut microbiota interacts with the brain through the microbiota-gut-brain axis, regulating physiological processes and impacting neurodevelopmental disorders. Researchers have identified three pathways through which the gut microbiota regulates neurodevelopment: the immune pathway, the neuronal pathway, and the endocrine/systemic pathway. This review provides an overview of research advancements in the microbiota-gut-brain axis in neurodevelopmental disorders and discusses the current state and future perspectives in this field.
Review
Cell Biology
Vanessa Hall, Katja Maria Sahlgren Bendtsen
Summary: The gut microbiome, gut barrier, and blood-brain barrier are crucial components of the gut-brain axis. Advances in organ-on-a-chip and iPSC technology could allow for more accurate modeling of the physiological functions of the gut-brain axis. It is important to develop non-animal models to study the complex gut-brain axis and its role in various brain disorders.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Medicine, Research & Experimental
Himanshi Yadav, Jaldhi, Rati Bhardwaj, Anamika, Amrita Bakshi, Suchi Gupta, Shashank Kumar Maurya
Summary: Emerging evidence suggests that gut microbiota plays a crucial role in regulating brain functions and maintaining brain homeostasis. Disturbed gut microbiota has been associated with various neurological diseases, while gut microbiome-derived exosomes have shown potential as therapeutic targets for neurodegenerative diseases. Pharmacological interventions, including antibiotics, prebiotics, and probiotics, can influence the management of neurological diseases mediated by the gut microbiome. However, further research is needed to enhance our understanding of the gut-brain connection and its implications for neurological diseases.
Review
Medicine, Research & Experimental
Yukun Liu, Ligang Xu, Zhaohui Yang, Dongfang Wang, Tianyu Li, Fan Yang, Zhanfei Li, Xiangjun Bai, Yuchang Wang
Summary: The review discusses the link between alterations in the intestinal microbiota and the development of septic myopathy, and critically evaluates the potential mechanisms and therapeutic prospects of modulating the gut microbiota.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Psychology, Multidisciplinary
Yanisa Wannasuphoprasit, Stig Ejdrup Andersen, Maria J. Arranz, Rosa Catalan, Gesche Jurgens, Sanne Maartje Kloosterboer, Henrik Berg Rasmussen, Anjali Bhat, Haritz Irizar, Dora Koller, Renato Polimanti, Baihan Wang, Eirini Zartaloudi, Isabelle Austin-Zimmerman, Elvira Bramon
Summary: The CYP2D6 genetic variation may influence weight gain in individuals taking antipsychotic medications, but further large-scale studies are needed to confirm the association.
FRONTIERS IN PSYCHOLOGY
(2022)
Article
Neurosciences
Prabhjot Dhami, Lena C. Quilty, Benjamin Schwartzmann, Rudolf Uher, Timothy A. Allen, Stefan Kloiber, Raymond W. Lam, Glenda MacQueen, Benicio N. Frey, Roumen Milev, Daniel J. Mueller, Stephen C. Strother, Pierre Blier, Claudio N. Soares, Sagar V. Parikh, Gustavo Turecki, Jane A. Foster, Susan Rotzinger, Sidney H. Kennedy, Faranak Farzan
Summary: The neurobiological correlates of response inhibition can predict the response of patients with major depressive disorder (MDD) to pharmacological and cognitive behavioral therapy treatment. The integrity of response inhibition may be crucial for the success of treatment for MDD. Electrophysiological correlates of response inhibition may serve as a general prognostic marker for treatment response in MDD.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2023)
Article
Pharmacology & Pharmacy
Helena K. Kim, Gwyneth Zai, Daniel J. Mueller, Muhammad Husain, Raymond W. Lam, Benicio N. Frey, Claudio N. Soares, Sagar Parikh, Roumen Milev, Jane A. Foster, Gustavo Turecki, Faranak Farzan, Benoit H. Mulsant, Sidney H. Kennedy, Shreejoy J. Tripathy, Stefan Kloiber
Summary: This study explores the relationship between the endocannabinoidome and major depressive disorder (MDD), and identifies lower methylation levels of the DAGLA gene as a potential marker for treatment outcomes in MDD. Further research is needed to explore the significance of DAGLA methylation in MDD treatment.
PHARMACOPSYCHIATRY
(2022)
Article
Psychology, Clinical
Mehri Sajjadian, Rudolf Uher, Keith Ho, Stefanie Hassel, Roumen Milev, Benicio N. Frey, Faranak Farzan, Pierre Blier, Jane A. Foster, Sagar Parikh, Daniel J. Mueller, Susan Rotzinger, Claudio N. Soares, Gustavo Turecki, Valerie H. Taylor, Raymond W. Lam, Stephen C. Strother, Sidney H. Kennedy
Summary: Predicting treatment outcomes for major depressive disorder can be improved by combining clinical, neuroimaging, and molecular data. Early measurement during treatment can increase precision, but adding more features does not necessarily enhance prediction accuracy.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Clinical Neurology
Megan Mio, Anahit Grigorian, Yi Zou, Mikaela K. Dimick, Beth Selkirk, Peter Kertes, Brian W. McCrindle, Walter Swardfager, Margaret K. Hahn, Sandra E. Black, Bradley J. MacIntosh, Benjamin I. Goldstein
Summary: This study reveals an association between retinal vascular caliber and cerebral blood flow in adolescents with bipolar disorder. These findings provide important insights into the potential neurofunctional mechanisms linking retinal vascular caliber with psychiatric diagnoses.
JOURNAL OF AFFECTIVE DISORDERS
(2023)
Article
Pharmacology & Pharmacy
Nicolette Stogios, Margaret K. Hahn, Yona Lunsky, Pushpal Desarkar, Sri Mahavir Agarwal
Summary: This case series reports on the clinical use of metformin in patients with intellectual and developmental disabilities (IDDs) on antipsychotics. The study found that patients experienced a mean weight loss of 11.1 kg while on metformin treatment, with over 50% achieving clinically meaningful weight loss of >7%.
JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Ian Seguin, Kyle D. Medak, Hesham Shamshoum, Margaret K. Hahn, David C. Wright
Summary: This study aimed to determine whether housing mice at thermoneutrality and under conditions of preexisting obesity would uncover a greater obesogenic effect of the antipsychotic olanzapine (OLZ). The study found that irrespective of obesity, OLZ treatment attenuated weight gain and increased energy expenditure in male mice. In females with preexisting obesity, OLZ increased food intake and potentiated weight gain. Uncovering the mechanisms conferring resistance to weight gain in males may provide clues for approaches to counter the metabolic side effects of antipsychotics clinically.
Editorial Material
Neurosciences
Nicolette Stogios, Margaret K. K. Hahn, Yona Lunsky, Pushpal Desarkar, Sri Mahavir Agarwal
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2023)
Review
Psychiatry
Sri Mahavir Agarwal, Nicolette Stogios, Guy E. J. Faulkner, Margaret Hahn
Summary: Patients with schizophrenia suffer from obesity, cardiovascular disease, and reduced life expectancy. The weight gain and metabolic adverse effects caused by antipsychotic medications exacerbate and accelerate these problems. Therefore, it is essential to develop safe and effective strategies for managing these issues as early as possible.
SCHIZOPHRENIA BULLETIN
(2023)
Review
Psychiatry
Femin Prasad, Margaret K. Hahn, Araba F. Chintoh, Gary Remington, George Foussias, Martin Rotenberg, Sri Mahavir Agarwal
Summary: Caregivers of people with schizophrenia often experience depression, but their mental health is often overlooked. This review aimed to consolidate recent literature on the prevalence of depression in these caregivers, factors associated with depression, and interventions that target depression. The findings suggest a high prevalence of depression in caregivers, with several factors influencing its occurrence, and promising interventions showing a significant reduction in depression levels.
SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Kyle D. Medak, Alyssa J. Weber, Hesham Shamshoum, Greg L. McKie, Margaret K. Hahn, David C. Wright
Summary: This study aimed to determine if increasing endogenous GLP1 is sufficient to protect against acute olanzapine-induced impairments in glucose and lipid homeostasis. The researchers found that pharmacological approaches to increase endogenous GLP1 can reduce lipid and glucose metabolism disturbances caused by olanzapine. These findings suggest that increasing endogenous GLP1 through pharmacological means may be a useful adjunct approach to mitigate olanzapine-induced perturbations in lipid and glucose metabolism.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Psychiatry
Jiwon Lee, Kenya Costa-Dookhan, Kristoffer Panganiban, Nicole MacKenzie, Quinn Casuccio Treen, Araba Chintoh, Gary Remington, Daniel J. J. Mueller, Sanjeev Sockalingam, Philip Gerretsen, Marcos Sanches, Alla Karnovsky, Kathleen A. Stringer, Vicki L. L. Ellingrod, Ivy F. F. Tso, Stephan F. F. Taylor, Sri Mahavir Agarwal, Margaret K. K. Hahn, Kristen M. M. Ward
Summary: Psychosis spectrum disorders (PSDs) and other severe mental illnesses like bipolar disorder are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the main treatment for PSDs, can lead to additional metabolic issues including weight gain. This study used metabolomic profiles to identify biomarkers and explore the mechanisms of PSDs and AP-induced weight gain. The findings suggest that specific fatty acids may serve as biomarkers for PSDs and early predictors of AP-induced weight gain. These findings have important clinical implications for identifying individuals at risk and developing targeted treatments.
FRONTIERS IN PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Femin Prasad, Riddhita De, Vittal Korann, Araba F. Chintoh, Gary Remington, Bjorn H. Ebdrup, Dan Siskind, Filip Krag Knop, Tina Vilsboll, Anders Fink-Jensen, Margaret K. Hahn, Sri Mahavir Agarwal
Summary: Metformin is the recommended first-line treatment for antipsychotic-associated weight gain (AAWG), but not all patients benefit from it. GLP1-RA has shown potential in managing obesity, and semaglutide, a weekly injectable GLP-1RA, has superior efficacy. This study explored the efficacy of semaglutide in AAWG and found significant weight loss in patients who did not respond to metformin. Further randomized control trials are needed to validate these findings.
THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY
(2023)
Review
Endocrinology & Metabolism
Sandra Pereira, Emily Au, Sri Mahavir Agarwal, David C. Wright, Margaret K. Hahn
Summary: Schizophrenia is a debilitating psychiatric disorder that is treated with antipsychotics. However, these medications have been found to increase the risk of metabolic and cardiovascular disorders, partly due to their effects on lipid metabolism. This review summarizes the current understanding of how antipsychotics modulate lipid turnover at different levels and highlights the need for further research on the intracellular mechanisms involved.
Review
Pharmacology & Pharmacy
Raghunath Singh, Nicolette Stogios, Emily Smith, Jiwon Lee, Kateryna Maksyutynsk, Emily Au, David C. Wright, Giada De Palma, Ariel Graff-Guerrero, Philip Gerretsen, Daniel J. Muller, Gary Remington, Margaret Hahn, Sri Mahavir Agarwal
Summary: This scoping review examines the role of gut microbiota (GMB) in the pathophysiology of schizophrenia (SCZ) and metabolic alterations associated with antipsychotics (APs). The findings suggest that changes in GMB composition are associated with SCZ pathogenesis and AP-induced metabolic perturbations. Additionally, prebiotic and probiotic formulations show potential therapeutic benefits in improving SCZ symptoms and attenuating AP-induced metabolic alterations.
THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY
(2022)
Article
Neurosciences
Oliver Pain, Karen Hodgson, Vassily Trubetskoy, Stephan Ripke, Victoria S. Marshe, Mark J. Adams, Enda M. Byrne, Adrian I. Campos, Tania Carrillo-Roa, Annamaria Cattaneo, Thomas D. Als, Daniel Souery, Mojca Z. Dernovsek, Chiara Fabbri, Caroline Hayward, Neven Henigsberg, Joanna Hauser, James L. Kennedy, Eric J. Lenze, Glyn Lewis, Daniel J. Mueller, Nicholas G. Martin, Benoit H. Mulsant, Ole Mors, Nader Perroud, David J. Porteous, Miguel E. Renteria, Charles F. Reynolds, Marcella Rietschel, Rudolf Uher, Eleanor M. Wigmore, Wolfgang Maier, Naomi R. Wray, Katherine J. Aitchison, Volker Arolt, Bernhard T. Baune, Joanna M. Biernacka, Guido Bondolfi, Katharina Domschke, Masaki Kato, Qingqin S. Li, Yu-Li Liu, Alessandro Serretti, Shih-Jen Tsai, Gustavo Turecki, Richard Weinshilboum, Andrew M. McIntosh, Cathryn M. Lewis
Summary: Antidepressant response is influenced by common genetic variation, has a genetic overlap with schizophrenia and educational attainment, and provides a useful resource for future research.
BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE
(2022)