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
Health Care Sciences & Services
Diana Z. Paderina, Anastasiia S. Boiko, Ivan V. Pozhidaev, Anna V. Bocharova, Irina A. Mednova, Olga Yu. Fedorenko, Elena G. Kornetova, Anton J. M. Loonen, Arkadiy V. Semke, Nikolay A. Bokhan, Svetlana A. Ivanova
Summary: The study investigated the association of nine polymorphisms in serotonergic system genes with MetS in patients with schizophrenia. Results suggested that allelic variants of HTR2C genes may affect metabolic parameters, and MetS is too complex to be studied without dissecting it into individual components.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Maarten Bak, Marjan Drukker, Shauna Cortenraad, Emma Vandenberk, Sinan Guloksuz
Summary: This meta-analysis found that antipsychotics are associated with body weight gain, regardless of psychiatric diagnosis.
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
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
Cell Biology
Shangang Zhao, Qian Lin, Wei Xiong, Li Li, Leon Straub, Dinghong Zhang, Rizaldy Zapata, Qingzhang Zhu, Xue-Nan Sun, Zhuzhen Zhang, Jan-Bernd Funcke, Chao Li, Shiuhwei Chen, Yi Zhu, Nisi Jiang, Guannan Li, Ziying Xu, Steven C. Wyler, May-Yun Wang, Juli Bai, Xianlin Han, Christine M. Kusminski, Ningyan Zhang, Zhiqiang An, Joel K. Elmquist, Olivia Osborn, Chen Liu, Philipp E. Scherer
Summary: Antipsychotic drugs can cause weight gain and diabetes, and hyperleptinemia plays a key role. Suppression of leptin rise can reduce the adverse effects of these drugs.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Psychology, Developmental
Hua Chen, Ning Lyu, Wenyaw Chan, Austin De La Cruz, Chadi Calarge
Summary: This study examines the utilization and predictors of adjuvant metformin among pediatric recipients of second-generation antipsychotics. The findings suggest that the utilization of adjuvant metformin is uncommon among pediatric SGA recipients, and early introduction of the medication among nonobese children is rare.
JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
(2023)
Review
Endocrinology & Metabolism
Helene Speyer, Casper Westergaard, Nikolai Albert, Mette Karlsen, Anne Emilie Sturup, Merete Nordentoft, Jesper Krogh
Summary: The study found that reducing dosage, discontinuing medication, or switching to a partial agonist can lead to a small but significant weight loss of around 1.5 kg. The overall weight change from pre to post intervention was a reduction of 1.13 kg.
FRONTIERS IN ENDOCRINOLOGY
(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
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
Chemistry, Medicinal
Jianping Chen, Erik J. Garcia, Christina R. Merritt, Joshua C. Zamora, Andrew A. Bolinger, Konrad Pazdrak, Susan J. Stafford, Randy C. Mifflin, Eric A. Wold, Christopher T. Wild, Haiying Chen, Noelle C. Anastasio, Kathryn A. Cunningham, Jia Zhou
Summary: In this study, novel oleamide analogues were designed and synthesized as selective 5-HT2CR agonists or dual 5-HT2CR/5-HT2AR positive allosteric modulators using a fragment-based discovery approach. Compound 13 (JPC0323) showed on-target properties, acceptable plasma exposure and brain penetration, and negligible displacement to orthosteric sites of over 50 GPCRs and transporters. Moreover, compound 13 suppressed novelty-induced locomotor activity in a 5-HT2CR-dependent manner, indicating 5-HT2CR agonist activity at the whole organism level at the employed doses of 13. This research discovered new selective 5-HT2CR agonists and first-in-class 5-HT2CR/5-HT2AR dual positive allosteric modulators, expanding the pharmacological toolbox for exploring the biology of these important receptors.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Anna Partyka, Katarzyna Gorecka, Joanna Gdula-Argasinska, Natalia Wilczynska-Zawal, Magdalena Jastrzebska-Wiesek, Anna Wesolowska
Summary: Patients taking antipsychotic drugs have a higher likelihood of developing metabolic syndrome, characterized by abdominal obesity, elevated glucose levels, and dyslipidemia. Current treatments for the metabolic side effects of antipsychotic drugs are not satisfactory. Ligands of the serotonin 6 receptor may offer a promising supplement to antipsychotic therapy. This study examined the effects of different antipsychotic drugs alone and in combination with a selective 5-HT6 agonist or antagonist on weight gain, food intake, lipid profile, glucose level, and adipose and gastrointestinal hormones in rats.
Article
Biochemistry & Molecular Biology
Qi Mao, Bingjie Zhang, Sheng Tian, Wangzhi Qin, Jiaojiao Chen, Xi-Ping Huang, Ye Xin, Huicui Yang, Xue-Chu Zhen, Wenqing Shui, Na Ye
Summary: The concept of subtype selectivity and functional bias has had a significant impact on GPCR drug discovery. Through synthesis and evaluation, a series of new N-H aporphines were found to be potent and selective 5-HT2C receptor agonists. These agonists with an exclusive bias towards Gq signaling have the potential to be valuable pharmacological tools for understanding therapeutically relevant 5-HT2C signaling pathways and developing alternative antipsychotic medications.
BIOORGANIC CHEMISTRY
(2022)
Article
Psychiatry
Bea Campforts, Marjan Drukker, Joost Crins, Therese van Amelsvoort, Maarten Bak
Summary: Previous meta-analyses have shown that most antipsychotics are associated with weight gain, but the extent of clinically relevant weight gain or weight loss varies. This study assessed the proportion of patients experiencing clinically relevant weight gain or weight loss when using antipsychotics, and found that almost all antipsychotics were associated with weight gain. Switching antipsychotic medication was also found to be associated with both weight gain and weight loss, with the level of weight gain being higher than weight loss.
Article
Nutrition & Dietetics
Jerusa da Mota Santana, Marcos Pereira, Gisele Queiroz Carvalho, Maria do Carmo Gouveia Peluzio, Iuri Drumond Louro, Djanilson Barbosa dos Santos, Ana Marlucia Oliveira
Summary: The polymorphisms of fatty acid desaturase genes FADS1 and FADS2 are associated with weight gain, while SNP rs174575 on FADS2 gene has a significant positive direct effect on gestational weight gain. In terms of plasma concentrations of PUFAs, SNP rs174561 and rs174575 have adverse effects on omega-3 fatty acid levels, and SNP rs174575 has positive effects on ARA and ARA/LA ratio, omega-6 products.
Editorial Material
Clinical Neurology
Gavin P. Reynolds, Olga O. McGowan
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Genetics & Heredity
Sri-Arun Iamjan, Samur Thanoi, Paritat Watiktinkorn, Helene Fachim, Caroline F. Dalton, Sutisa Nudmamud-Thanoi, Gavin P. Reynolds
Summary: The study investigated the effects of methamphetamine on DNA methylation of BDNF in humans and rats, finding increased methylation in patients and rats with METH exposure. These changes may affect BDNF expression and contribute to the neurotoxic effects of METH.
Article
Genetics & Heredity
Camila M. Loureiro, Helene A. Fachim, Fabiana Corsi-Zuelli, Rosana Shuhama, Paulo R. Menezes, Caroline F. Dalton, Cristina M. Del-Ben, Gavin P. Reynolds, Paulo Louzada-Junior
Summary: The study found that childhood trauma may influence DNA methylation in individuals with a predisposition to psychosis, but not in those with frank schizophrenia or controls.
Letter
Clinical Neurology
Gavin P. Reynolds
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Editorial Material
Clinical Neurology
Gavin P. Reynolds
Summary: Guidelines for schizophrenia treatment emphasize the importance of dosage and mechanism of action, particularly highlighting the benefits of partial agonist drugs in reducing side effects while maintaining efficacy.
JOURNAL OF PSYCHOPHARMACOLOGY
(2021)
Article
Clinical Neurology
Helene A. Fachim, Fabiana Corsi-Zuelli, Camila M. Loureiro, Sri-arun Iamjan, Rosana Shuhama, Samia Joca, Paulo Rossi Menezes, Adrian Heald, Paulo Louzada-Junior, Caroline F. Dalton, Cristina Marta Del-Ben, Gavin P. Reynolds
Summary: The study suggests that childhood maltreatment may result in increased BDNF methylation, providing a mechanism underlying the association between early-life stress and psychosis.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Editorial Material
Genetics & Heredity
Gavin P. Reynolds
Meeting Abstract
Clinical Neurology
H. Fachim, C. Loureiro, F. Corsi-Zuelli, P. Rossi-Menezes, P. Louzada-, C. Dalton, A. Heald, C. M. Del-Ben, G. Reynolds
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Clinical Neurology
Gavin P. Reynolds
Summary: Research in Peter Riederer's lab in Vienna in the late 1970s stemmed from a strong tradition in post-mortem neurochemical studies, acknowledging the value of post-mortem brain tissue in understanding pharmacological mechanisms of neuropsychiatric treatments. Investigating dopamine, D2 receptors, and GABAergic neurons led to the discovery of deficits associated with schizophrenia. Subsequent research on DNA methylation of the parvalbumin gene aims to further understand these findings in psychotic illness and its animal models.
JOURNAL OF NEURAL TRANSMISSION
(2022)
Article
Clinical Neurology
Camila M. Loureiro, Helene A. Fachim, Michael K. Harte, Caroline F. Dalton, Gavin P. Reynolds
Summary: This study investigated the DNA methylation and protein expression changes in NMDAR subunits in the prefrontal cortex and hippocampus of rats after subchronic PCP administration. The results showed hypermethylation of Grin1 and Grin2b promoters and reduction in NR1 protein levels. These alterations may contribute to the pathogenesis of schizophrenia.
JOURNAL OF PSYCHOPHARMACOLOGY
(2022)
Article
Immunology
Keke Hao, Huiling Wang, Yuejin Zhang, Xinhui Xie, Huan Huang, Cheng Chen, Shilin Xu, Rui Xu, Chang Shu, Zhongchun Liu, Yuan Zhou, Gavin P. Reynolds, Gaohua Wang
Summary: Early life stress may lead to schizophrenia-like phenotypes and persistent hippocampal abnormalities. Nicotinamide may be a safe and effective treatment in adolescence to restore normal hippocampal function and prevent or ameliorate schizophrenia-like behavior.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Psychiatry
David Taylor, Ramalingam Chithiramohan, Jasdev Grewal, Avirup Gupta, Lars Hansen, Gavin P. Reynolds, Sofia Pappa
Summary: There are three marketed dopamine D2 partial agonists worldwide: aripiprazole, brexpiprazole, and cariprazine. These drugs have similar pharmacological properties and clinical effects, including being effective antipsychotics with antimanic and antidepressant activity. They are well tolerated with minimal side effects and have a low risk of increased prolactin, weight gain, and tardive dyskinesia.
INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE
(2023)
Article
Psychiatry
John Cookson, Jonathan Pimm, Gavin Reynolds
Summary: This study examines the effects of combining partial agonists and full antagonists in the treatment of psychosis and analyzes the impact of the dopamine hypothesis on treatment outcomes. The combinations considered include aripiprazole with amisulpride, with risperidone in people with hyperprolactinaemia, and with olanzapine to mitigate weight gain. The study discusses the potential worsening of symptoms by adding or switching to a partial agonist and explores the adverse interaction with a full antagonist, such as haloperidol, during a subsequent relapse to control severe agitation.
Letter
Endocrinology & Metabolism
Gavin P. Reynolds
Article
Psychology, Clinical
Yamin Zhang, Qiang Wang, Gavin P. Reynolds, Weihua Yue, Wei Deng, Hao Yan, Liwen Tan, Chuanyue Wang, Guigang Yang, Tianlan Lu, Lifang Wang, Fuquan Zhang, Jianli Yang, Keqing Li, Luxian Lv, Qingrong Tan, Yinfei Li, Hua Yu, Hongyan Zhang, Xin Ma, Fude Yang, Lingjiang Li, Qi Chen, Wei Wei, Liansheng Zhao, Huiyao Wang, Xiaojing Li, Wanjun Guo, Xun Hu, Yang Tian, Hongyan Ren, Xiaohong Ma, Jeremy Coid, Dai Zhang, Tao Li
JOURNAL OF CLINICAL PSYCHIATRY
(2020)