Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic variation in antipsychotic drug targets could underlie variability among patients in the time required for antipsychotic effects to be elicited. In a clinical, pharmacogenetic study we focused on the dopamine receptor interacting protein (DRIP) gene family. DRIPs are pivotally involved in regulating dopamine receptor signal transduction. Consecutively hospitalized, acutely psychotic patients with DSM-IV schizophrenia (n=121) were included in the study if they received treatment with typical antipsychotic medication (TYP, n=72) or TYP plus risperidone (TYP-R, n=49) for at least 2 wk. Clinical state and adverse effects were rated at baseline and after 2 wk. Patients improved significantly on both TYP and TYP-R with no significant difference between them. Early responders were defined as patients whose PANSS change scores were greater than the median. Twenty-two single nucleotide polymorphisms (SNPs) were analysed in five DRIP-encoding genes. Two SNPs in NEF3, which encodes the DRIP, neurofilament-medium (NF-M), were associated with early response (rs1457266, p=0.01; rs1379357, p=0.006). A 5 SNP haplotype spanning NEF3 was over-represented in early responders (p=0.015), in the combined patient group and in the TYP group alone. These findings suggest that variation in NEF3, most likely functional variants that are in linkage disequilibrium with the SNPs that we studied, influences rate of response to TYP. Since NEF3 is primarily associated with dopamine D1 receptor function, the evidence for a complementary role of dopamine D1 receptors in antipsychotic effects is considered. The findings reported here open an interesting research avenue in the pharmacogenetics of antipsychotic effects but require replication in larger samples treated in a controlled context.
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PMID:Association of the dopamine receptor interacting protein gene, NEF3, with early response to antipsychotic medication. 1673 40

Schizophrenia is a severe debilitating brain disorder with a poorly understood aetiology. Among the diverse aetiological clues lies evidence for immune abnormalities in some individuals. The aim of this study was to investigate the frequency and specificity of autoantibodies directed against the brain in people with schizophrenia. Sera were screened for reactivity against human brain tissue (hippocampus and prefrontal cortex). Neuronal cell body and filamentous patterns of brain tissue staining were observed significantly more frequently in sera from schizophrenia patients (n=30) compared to controls (n=24). Sera that showed a neuronal cell body pattern of staining on hippocampus reacted strongly to an extracellular epitope of the M1 muscarinic acetylcholine receptor (m1AChR) in ELISA. Both cell body staining and elevated m1AChR reactivity correlated with higher symptom scores for poverty of speech. Sera showing a filamentous staining pattern predominantly targeted microfilaments, intermediate filaments or neurofilaments, particularly neurofilament medium (NFM), which is a dopamine receptor interacting protein. By ELISA, there was strongly elevated reactivity against NFM in a subset (15%) of schizophrenia patients (n=101) compared to healthy controls (n=55) or patients with multiple sclerosis (n=32). These results support the hypothesis that neurotransmitter receptors or molecules involved in regulation of neurotransmission are targets of autoantibodies in some people with schizophrenia.
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PMID:Elevated levels of autoantibodies targeting the M1 muscarinic acetylcholine receptor and neurofilament medium in sera from subgroups of patients with schizophrenia. 2463 2