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COMT antipsychotic response

Marco Calabrò, Stefano Porcelli, Concetta Crisafulli, Sheng-Min Wang, Soo-Jung Lee, Changsu Han, Ashwin A Patkar, Prakash S Masand, Diego Albani, Ilaria Raimondi, Gianluigi Forloni, Sofia Bin, Carlotta Cristalli, Vilma Mantovani, Chi-Un Pae, Alessandro Serretti
Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk...
January 2018: Journal of Molecular Neuroscience: MN
Mercedes Zumárraga, Aurora Arrúe, Nieves Basterreche, Isabel Macías, Ana Catalán, Arantza Madrazo, Sonia Bustamante, María I Zamalloa, Leire Erkoreka, Estibaliz Gordo, Ainara Arnaiz, Olga Olivas, Ariane Arroita, Elena Marín, Miguel A González-Torres
AIM: We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. PATIENTS & METHODS: We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. RESULTS: Bipolar patients: haplotypes are associated with age at onset and clinical evolution...
June 2016: Pharmacogenomics
Eric Huang, Clement C Zai, Amanda Lisoway, Malgorzata Maciukiewicz, Daniel Felsky, Arun K Tiwari, Jeffrey R Bishop, Masashi Ikeda, Patricio Molero, Felipe Ortuno, Stefano Porcelli, Jerzy Samochowiec, Pawel Mierzejewski, Shugui Gao, Benedicto Crespo-Facorro, José M Pelayo-Terán, Harpreet Kaur, Ritushree Kukreti, Herbert Y Meltzer, Jeffrey A Lieberman, Steven G Potkin, Daniel J Müller, James L Kennedy
BACKGROUND: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response...
May 2016: International Journal of Neuropsychopharmacology
Cristiano Noto, Vanessa Kiyomi Ota, Marcos Leite Santoro, Eduardo Sauerbronn Gouvea, Patricia Natalia Silva, Leticia Maria Spindola, Quirino Cordeiro, Rodrigo Affonseca Bressan, Ary Gadelha, Elisa Brietzke, Sintia Iole Belangero, Michael Maes
In schizophrenia, genetic and environmental factors affect neurodevelopment and neuroprogressive trajectory. Altered expression of neuro-immune genes and increased levels of cytokines are observed, especially in patients with comorbid depression. However, it remains unclear whether circulating levels of cytokines and expression of these genes are associated, and how antipsychotic treatments impact this association. Relationships between messenger RNA (mRNA) expression of 11 schizophrenia-related genes and circulating levels of cytokines (interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α) were analyzed in 174 antipsychotic naïve first episode psychosis (FEP) and in 77 healthy controls...
October 2016: Molecular Neurobiology
Q Xu, X Wu, M Li, H Huang, C Minica, Z Yi, G Wang, L Shen, Q Xing, Y Shi, L He, S Qin
Schizophrenia is a widespread mental disease with a prevalence of about 1% in the world population. Continuous long-term treatment is required to maintain social functioning and prevent symptom relapse of schizophrenia patients. However, there are considerable individual differences in response to the antipsychotic drugs. There is a pressing need to identify more drug-response-related markers. But most pharmacogenomics of schizophrenia have typically focused on a few candidate genes in small sample size. In this study, 995 subjects were selected for discovering the drug-response-related markers...
August 2016: Pharmacogenomics Journal
Hui Chen, Jiao Tu, Ping Ni, Wei Zhang, Linyong Xu
OBJECTIVE: To examine the relationship between COMT polymorphisms and the response to antipsychotic drugs, and then provide a basis for personalized medicine of antipsychotic drugs.
 METHODS: We performed a systematic search from PubMed, Embase, Cochrane Library, CBM, CNKI, VIP and Wanfang database for eligible studies. Stata 12.0 was used for Meta-analysis after evaluating the quality of studies and collecting the data.
 RESULTS: Nine studies included 868 participants met inclusion criteria...
June 2015: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
Z Naumovska, A K Nestorovska, A Filipce, Z Sterjev, K Brezovska, A Dimovski, L J Suturkova
Antipsychotic drugs are widely used in the treatment of schizophrenia and psychotic disorder. The lack of antipsychotic response and treatment-induced side-effects, such as neuroleptic syndrome, polydipsia, metabolic syndrome, weight gain, extrapyramidal symptoms, tardive dyskinesia or prolactin increase, are the two main reasons for non-compliance and increased morbidity in schizophrenic patients. During the past decades intensive research has been done in order to determine the influence of genetic variations on antipsychotics dosage, treatment efficacy and safety...
2015: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
Marta Bosia, Cristina Lorenzi, Adele Pirovano, Carmelo Guglielmino, Federica Cocchi, Marco Spangaro, Placido Bramanti, Enrico Smeraldi, Roberto Cavallaro
AIM: Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems...
January 2015: Pharmacogenomics
Jeffrey R Bishop, James L Reilly, Margret S H Harris, Shitalben R Patel, Rick Kittles, Judith A Badner, Konasale M Prasad, Vishwajit L Nimgaonkar, Matcheri S Keshavan, John A Sweeney
RATIONALE: Type-3 metabotropic glutamate receptor gene (GRM3) single nucleotide polymorphisms (SNPs) have been associated with cognitive performance and prefrontal cortex brain activity in chronically treated schizophrenia patients. Whether these SNPs are associated with cognitive and symptom response to antipsychotic therapy has not been extensively evaluated. OBJECTIVES: The aim of the study was to examine pharmacogenetic relationships between GRM3 and selected variants in relevant dopamine genes with changes in spatial working memory and clinical symptoms after treatment...
January 2015: Psychopharmacology
Marta Bosia, Andrea Zanoletti, Marco Spangaro, Mariachiara Buonocore, Margherita Bechi, Federica Cocchi, Adele Pirovano, Cristina Lorenzi, Placido Bramanti, Enrico Smeraldi, Roberto Cavallaro
Cognitive remediation is the best available tool to treat cognitive deficits in schizophrenia and has evidence of biological validity; however results are still heterogeneous and significant predictors are lacking. Previous studies showed that cognitive remediation is able to induce changes in PFC function and dopaminergic transmission and thus the study of possible sources of variability at these levels (i.e. antipsychotic treatments and genetic variability) might help to gain a deeper understanding of neurobiological correlates and translate into optimization and personalization of interventions...
June 30, 2014: Psychiatry Research
Julia Diemer, Katharina Domschke, Andreas Mühlberger, Bernward Winter, Maxim Zavorotnyy, Swantje Notzon, Karen Silling, Volker Arolt, Peter Zwanzger
Anxiety disorders are among the most frequent psychiatric disorders. With regard to pharmacological treatment, antidepressants, the calcium modulator pregabalin and benzodiazepines are recommended according to current treatment guidelines. With regard to acute states of anxiety, so far practically only benzodiazepines provide an immediate anxiolytic effect. However, the risk of tolerance and dependency limits the use of this class of medication. Therefore, there is still a need for alternative pharmacologic strategies...
November 2013: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Adrián Llerena, Roland Berecz, Eva Peñas-Lledó, Agnes Süveges, Humberto Fariñas
Despite risperidone's proven safety and efficacy, existing pharmacogenetic knowledge could be applied to improve its clinical use. The present work aims to summarize the information about genetic polymorphisms affecting risperidone adverse reactions and efficacy during routine clinical practice. The most relevant genes involved in the metabolism of the drug (i.e., CYP2D6, CYP3A and ABCB1) appear to have the greatest potential to predict differences in plasma concentrations of the drug and its interactions, but also relate to side effects, such as neuroleptic syndrome, weight gain or polydipsia...
January 2013: Pharmacogenomics
Qing-Zhu Zhao, Bao-Cheng Liu, Jing Zhang, Lei Wang, Xing-Wang Li, Yang Wang, Jue Ji, Feng-Ping Yang, Chun-Ling Wan, Yi-Feng Xu, Guo-Yin Feng, Lin He, Guang He
A total of 130 Chinese schizophrenic patients (45 male, 85 female) were enrolled in the study. Clinical efficacy was determined using Brief Psychiatric Rating Scale (BPRS) scores. We genotyped 10 single-nucleotide polymorphisms (SNPs) of the catechol-O-methyl transferase gene (COMT) in our patients and re-examined them for association with changes in BPRS scores after 8 weeks of risperidone monotherapy. COMT is one of the genes that confer susceptibility to schizophrenia, both because of its role in neurotransmitter metabolism and because of its location in the high-risk schizophrenia-related region 22q11...
December 2012: Psychiatric Genetics
Piotr Tybura, Agnieszka Samochowiec, Aleksander Beszlej, Anna Grzywacz, Monika Mak, Dorota Frydecka, Przemysław Bieńkowski, Paweł Mierzejewski, Andrzej Potemkowski, Jerzy Samochowiec
BACKGROUND: Therapeutic effects of all clinically used antipsychotics are related to the reduction of dopaminergic transmission in the limbic system. The aim of present study was two-fold. First, efficacy of atypical drugs (ziprasidone and olanzapine) against schizophrenia symptoms was compared to that offered by a typical antipsychotic medication, perazine. Second, associations between some dopaminergic genes polymorphisms and therapeutic response to antipsychotics were assessed in the same group of schizophrenia patients...
2012: Pharmacological Reports: PR
Tamar Green, Lital Steingart, Amos Frisch, Omer Zarchi, Abraham Weizman, Doron Gothelf
The goal of this trial was to assess the feasibility and safety of using S-adenosyl-L-methionine (SAMe) to treat depressive disorder, attention deficit/hyperactivity disorder (ADHD) and cognitive deficits in individuals with the 22q11.2 deletion syndrome (22q11.2DS). SAMe supposedly enhances the activity of the COMT enzyme. Because individuals with 22q11.2DS have only one copy of the gene responsible for the enzyme, COMT haploinsufficiency may be associated with their psychiatric morbidity and cognitive deficits...
November 2012: Journal of Neural Transmission
Shugui Gao, Zhenyu Hu, Jia Cheng, Wenhua Zhou, Yongming Xu, Shuguang Xie, Shiyan Liu, Zaizhong Li, Junming Guo, Jianyi Dong, Minfang Huang
OBJECTIVES: The main aim was to study the effects of COMT polymorphisms on response of risperidone treatment for schizophrenia and investigate the correlation between memory function of schizophrenia patients and COMT polymorphisms. DESIGN AND METHODS: Subjects were 83 schizophrenic patients who were antipsychotic drug free at the initiation of this study. Peripheral blood samples were obtained to identify COMT polymorphisms by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method...
July 2012: Clinical Biochemistry
Nienke C C Vulink, Herman G M Westenberg, Filip van Nieuwerburgh, Dieter Deforce, Sjoerd B A H A Fluitman, Jantien S C Meinardi, Damiaan Denys
OBJECTIVE: To determine whether polymorphisms of the dopamine D(2) receptor (DRD2) and catechol-O-methyl-transferase (COMT) receptor genes affect the efficacy of quetiapine addition to citalopram in patients with OCD. METHODS: Sixty-four drug-free or drug-naïve patients meeting DSM-IV criteria for OCD were randomized to 10 weeks double-blind treatment with citalopram (60 mg/day) with quetiapine (300 -450 mg/day) or with placebo. The change from baseline to endpoint on the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the response to treatment were the primary outcome measures...
October 2012: International Journal of Psychiatry in Clinical Practice
Jelle Vehof, Huibert Burger, Bob Wilffert, Asmar Al Hadithy, Behrooz Z Alizadeh, Harold Snieder
Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic treatment response. 329 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 9 SNPs in 6 candidate genes (DRD2: TaqI_A, -141C; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser; COMT: Val158Met; MTHFR: 677-C/T) using standard protocols...
September 2012: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
M Gupta, H Kaur, A Jajodia, S Jain, K Satyamoorthy, M Mukerji, J Thirthalli, R Kukreti
Dopaminergic system in the prefrontal cortex (PFC) is known to regulate the cognitive functions. Catechol-O-methyl transferase (COMT), one of the major modulators of prefrontal dopamine function, has emerged as an important determinant of schizophrenia associated cognitive dysfunction and response to antipsychotics. A common Val->Met polymorphism (rs4680) in the COMT gene, associated with increased prefrontal dopamine catabolism, impairs prefrontal cognition and might increase risk for schizophrenia. Further, the degree of cognitive improvement observed with antipsychotics in schizophrenia patients is influenced by the COMT activity, and Val/Met has been proposed as a potential pharmacogenetic marker...
December 2011: Current Molecular Medicine
Vincenzo De Luca, Renan P Souza, Emanuela Viggiano, Laertes Sickert, Celine Teo, Clement Zai, Arun K Tiwari, Daniel J Müller, Jeffery A Lieberman, Jan Volavka, Herbert Y Meltzer, James L Kennedy
UNLABELLED: Atypical antipsychotics (AP) have high affinity for many neurotransmitter receptors. Among these receptors, APs are antagonist at α-adrenergic and β-adrenergic receptors, and this pharmacological property has been postulated to be involved in the mechanism of action of these drugs with respect to both clinical response and adverse effects. OBJECTIVE: We tested the hypotheses that AP-induced weight gain is associated with genetic variation in adrenergic receptors and pathway enzymes...
August 2011: Human Psychopharmacology
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