rs1018381

This study examined the association of two DTNBP1 gene single nucleotide polymorphisms (rs2619522 and rs1018381) with hippocampal and prefrontal grey matter volumes in 72 subjects using voxel-based morphometry. The G allele of rs2619522 was associated with significantly higher grey matter volumes bilaterally in the hippocampus, anterior middle frontal gyrus, and intraparietal cortex (p < 0.001 uncorrected). The T allele of rs1018381 was associated with increased grey matter volumes bilaterally in frontal cortices, left lingual gyrus, right thalamus/pulvinar, and left cerebellum.

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

This fMRI study in 57 healthy male volunteers examined the influence of DTNBP1 SNP rs1018381 on working memory and brain activation during an N-back task. Risk-allele carriers (T/C genotype) showed significantly increased activation in bilateral middle frontal gyrus (BA 9, part of DLPFC) compared to noncarriers (C/C), despite no differences in behavioral performance, suggesting the genetic variant affects brain activation more sensitively than behavioral measures.

An fMRI study of 84 healthy subjects investigating the effect of DTNBP1 rs1018381 on neural activity during episodic memory tasks. Risk allele carriers (A/G genotype, n=29) showed significantly enhanced neural activity in the prefrontal cortex and parietal regions during both encoding and retrieval of faces compared to non-risk carriers (G/G, n=55), despite no behavioral performance differences. The enhanced activation may reflect compensatory cognitive mechanisms for genetically-influenced memory alterations.

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

This comprehensive review synthesizes genomic and pharmacogenomic research in schizophrenia, discussing over 200 candidate genes associated with psychotic disorders, genetic mechanisms including copy number variants and microRNA alterations, and pharmacogenomic factors affecting antipsychotic efficacy and safety. Key genes covered include dopamine receptors (DRD1-5), dysbindin (DTNBP1), DISC1, neurotrophic factors, and metabolic enzymes such as CYP2D6, CYP3A4, and COMT, with emphasis on genotype-phenotype correlations in antipsychotic response and side effects.

This association study tested whether DTNBP1 (dysbindin) polymorphisms are associated with schizophrenia diagnosis and clinical features in an Italian cohort of 80 schizophrenic patients and 106 healthy controls. A trend toward association was found for rs2619538 (P=0.058), and haplotype analysis identified three significant haplotypes: rs2619538-P1583 (P=0.048), P1320-P1757 (P=0.034), and rs2619538-P1583-P1578 (P=0.040). The rs2619538-P1583 haplotype was associated with more severe and persistent negative psychopathology, particularly motor retardation and hallucinations.