Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder.
Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder.
Schizophrenia (SZ) and bipolar disorder (BPD) patients show a downregulation of GAD67, reelin (RELN), brain-derived neurotrophic factor (BDNF), and other genes expressed in telencephalic GABAergic and glutamatergic neurons.
Schizophrenia (SZ) and bipolar disorder (BPD) patients show a downregulation of GAD67, reelin (RELN), brain-derived neurotrophic factor (BDNF), and other genes expressed in telencephalic GABAergic and glutamatergic neurons.
The copy number intensities examined using both microarrays and quantitative real-time polymerase chain reaction for the GAD67 gene were significantly decreased in sector CA3/2 of patients with schizophrenia and patients with bipolar disorder.
The copy number intensities examined using both microarrays and quantitative real-time polymerase chain reaction for the GAD67 gene were significantly decreased in sector CA3/2 of patients with schizophrenia and patients with bipolar disorder.
In schizophrenia and bipolar disorder, a network of genes involved in the regulation of GAD₆₇, a marker for the functional differentiation of GABA cells, show pronounced changes in expression and include kainate receptor subunits, TGFβ and Wnt signaling pathways, epigenetic factors and transcription factors.
The nature of these changes is quite different in schizophrenia and bipolar disorder, suggesting that a common cell phenotype (in this case, decreased GAD₆₇ expression) may involve two fundamentally different molecular endophenotypes and reflect unique susceptibility genes involved in the respective disorders.
This molecular remodeling may contribute to the induction of reelin (RELN) and GAD(67) (GAD1) promoter demethylation, and may reverse the downregulation of various GABAergic mRNAs and proteins detected in the telencephalon of patients with schizophrenia or bipolar disorders.
This is the first demonstration that there is more DNA fragmentation in cells showing no detectable GAD67 mRNA in patients with bipolar disorder than in schizophrenics or controls.
GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum.
A research strategy directed toward identifying specific neurochemical markers operative in the etiopathology of psychotic disorders lead to the identification of a downregulation (30-50%) of Reln and glutamic acid decarboxylase 67(GAD67) expression in prefrontal cortex and other brain areas of schizoprenia and bipolar disorder patients with psychosis.