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

CACNA1C-rs1006737 and ZNF804A-rs1344706 polymorphisms are among the most robustly associated with schizophrenia (SCZ) and bipolar disorder (BD), and recently with brain phenotypes. As these patients show abnormal verbal fluency (VF) and related brain activation, we asked whether the latter was affected by these polymorphisms (alone and in interaction)-to better understand how they might induce risk. We recently reported effects on functional VF-related (for ZNF804A-rs1344706) and structural (for both) connectivity. We genotyped and fMRI-scanned 54 SCZ, 40 BD and 80 controls during VF. With SPM, we assessed the main effect of CACNA1C-rs1006737, and its interaction with ZNF804A-rs1344706, and their interaction with diagnosis, on regional brain activation and functional connectivity (psychophysiological interactions-PPI). Using public data, we reported effects of CACNA1C-rs1006737 and diagnosis on brain expression. The CACNA1C-rs1006737 risk allele was associated with increased activation, particularly in the bilateral prefronto-temporal cortex and thalamus; decreased PPI, especially in the left temporal cortex; and gene expression in white matter and the cerebellum. We also found unprecedented evidence for epistasis (interaction between genetic polymorphisms) in the caudate nucleus, thalamus, and cingulate and temporal cortical activation; and CACNA1C up-regulation in SCZ and BD parietal cortices. Some effects were dependent on BD/SCZ diagnosis. All imaging results were whole-brain, voxel-wise, and familywise-error corrected. Our results support evidence implicating CACNA1C and ZNF804A in BD and SCZ, adding novel imaging evidence in clinical populations, and of epistasis-which needs further replication. Further scrutiny of the inherent neurobiological mechanisms may disclose their potential as putative drug targets.
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PMID:The effect of psychosis associated CACNA1C, and its epistasis with ZNF804A, on brain function. 3007 86

Investigations of brain structure in schizophrenia using magnetic resonance imaging (MRI) have identified variations in regional grey matter (GM) volume throughout the brain but the results are mixed. This study aims to investigate whether the inconsistent voxel-based morphometry (VBM) findings in schizophrenia are due to the use of different software packages. T1 MRI images were obtained from 86 first-episode schizophrenia (FESZ) patients and 86 age- and gender-matched Healthy controls (HCs). VBM analysis was carried out using FMRIB software library (FSL) 5.0 and statistical parametric mapping 8 (SPM8). All images were processed using the default parameter settings as provided by these software packages. FSL-VBM revealed widespread GM volume reductions in FESZ patients compared with HCs, however, for SPM-VBM, only increased and circumscribed GM volume changes were found, both software revealed increased GM volume within cerebellum. Significant correlations between Positive and Negative Syndrome Scale (PANSS) and GM volume were mainly found in frontal regions. Algorithms of GM tissue segmentation, image registration and statistical strategies might contribute to these disparate results.
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PMID:Voxel-based morphometry results in first-episode schizophrenia: a comparison of publicly available software packages. 3137 89


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