Study Report
Reference
| Citation | Sibille, 2011 PubMed |
| Full Info | Sibille, E., Morris, H.M., Kota, R.S. and Lewis, D.A. (2011) GABA-related transcripts in the dorsolateral prefrontal cortex in mood disorders. Int J Neuropsychopharmacol, 1-14.
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Study
| Hypothesis or Background |
Reduced cortical I(3)-aminobutyric acid (GABA) levels and altered markers for subpopulations of GABA interneurons have been reported in major depressive disorder (MDD) by in-vivo brain imaging and post-mortem histological studies. Subgroups of GABA interneurons exert differential inhibitory control on principal pyramidal neurons and can be identified based on the non-overlapping expression of the calcium-binding proteins parvalbumin (PV) or calretinin (CR) or the neuropeptide somatostatin (SST). As altered markers of GABAergic functions may also be present in bipolar disorder (BPD), the specificity of particular GABA-related molecular deficits in mood disorders is not known.
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| Sample Information | triads (n=19) of control subjects and matched subjects with BPD or MDD |
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| Method Detail | We used real-time quantitative polymerase chain reaction (qPCR) to assess expression levels of two GABA synthesizing enzymes (glutamate decarboxylase; GAD65 and GAD67) and of three markers of GABA neuron subpopulations (PV, CR, SST) in the dorsolateral prefrontal cortex (DLPFC; Brodmann area 9) in triads (n=19) of control subjects and matched subjects with BPD or MDD. |
| Method Keywords | Q-PCR |
| Result | 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. The characteristic age-related decline in SST expression was not observed in MDD, as low expression was detected across age in MDD subjects. After controlling for age, MDD subjects demonstrated significantly reduced SST mRNA expression. Decreased SST levels in MDD were confirmed at the protein precursor level. |
| Conclusions | Results were not explained by other clinical, demographic or technical parameters. In summary, MDD was characterized by low DLPFC SST, whereas decreased PV mRNA appears to distinguish BPD from MDD. |
Relationships reported by
Sibille, 2011
| Component A Approved Name (Name in Paper) |
Component A Type |
Component B Approved Name (Name in Paper) |
Component B Type |
Statistical Result |
Relationship Description |
Result Category (Positive/Negative)) |
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MDD
|
syndrome |
SST (neuropeptide somatostatin (SST)) |
gene |
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MDD subjects demonstrated reduced SST mRNA expression in the dorsolateral prefrontal cortex. |
Positive
|
|
MDD
|
syndrome |
Dorsolateral prefrontal cortex (dorsolateral prefrontal cortex) |
brain morphology and function |
|
MDD subjects demonstrated reduced SST mRNA expression in the dorsolateral prefrontal cortex. |
Positive
|
