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.
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 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 exploratory study provides an initial step for future studies to investigate an association between the reductions in SLC1A2 and GAD1 mRNA expression and their relation to the attenuation of the RAF/MEK/ERK signaling pathway in the dlPFC in MDD.
BPD subjects demonstrated significantly reduced PV mRNA, trend level reduction in SST mRNA and no alterations in GAD67, GAD65, or CR mRNA levels; MDD subjects demonstrated reduced SST mRNA expression without alterations in the other transcripts.
We report findings based on analyses of self-reports of six common adolescent psychopathologies (attention deficit/hyperactivity disorder, ADHD; conduct disorder, CD; oppositional defiant disorder, ODD; generalized anxiety disorder, GAD; separation anxiety disorder, SAD; and major depressive disorder, MDD) in a sample of 1,162 male and female adolescent (12-19 years) twin pairs and 426 siblings.
Subject to confirmation in an independent sample, our study suggests that variations in the GAD1 gene may contribute to individual differences in N and impact susceptibility across a range of anxiety disorders and major depression.
We also found suggestive associations in women for GAD1, GRIA3, and BDNF with depression accompanied by fatigue, and for CRHR1 with depression accompanied by early morning awakenings.
We also found suggestive associations in women for GAD1, GRIA3, and BDNF with depression accompanied by fatigue, and for CRHR1 with depression accompanied by early morning awakenings.
As a consequence broader entities such as depression-GAD spectrum, panic-phobias spectrum and OCD spectrum including eating disorders and pathological gambling are taken into consideration; (c) Diagnostic categories use thresholds to delimitate a border with normals.This creates "subthreshold" conditions.
As a consequence broader entities such as depression-GAD spectrum, panic-phobias spectrum and OCD spectrum including eating disorders and pathological gambling are taken into consideration; (c) Diagnostic categories use thresholds to delimitate a border with normals.This creates "subthreshold" conditions.
This is the first genetic study regarding the GAD67 gene in relation to the condition of alcohol dependence in an Italian population of subjects all coming from the same region (Veneto).
We first conducted case-control analyses of the GAD genes with AD and, within the cases, examined associations with age at onset of AD, withdrawal symptoms, and two quantitative measures: initial sensitivity and tolerance (based on scales from the Self-Rating of the Effects of Ethanol) [Schuckit, M.A., Smith, T.L., Tipp, J.E., 1997.
The test-retest reliability for the age of onset of major depression and panic disorder was excellent, and for phobia, GAD and alcoholism, was acceptable.
An association between the reduced levels of SLC1A2 and GAD1 in the dorsolateral prefrontal cortex in major depressive disorder: possible involvement of an attenuated RAF/MEK/ERK signaling pathway.