COMT antipsychotic response

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...

IMPORTANCE OF THE FIELD: Antipsychotic drug is the mainstay of treatment for schizophrenia, and there are large inter-individual differences in clinical response and side effects. Pharmacogenetics provides a valuable tool to fulfill the promise of personalized medicine by tailoring treatment based on one's genetic markers. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacogenetic literature from early 1990s to 2010, focusing on two aspects of drug action: pharmacokinetics and pharmacodynamics...