Abstract
Alterations in GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Glutamic acid decarboxylase (GAD) is the key enzyme in GABA synthesis. This study aimed to differentiate between unipolar and bipolar I depression using quantitative evaluation of GAD-immunoreactive (GAD-ir) neuropil in several brain regions known to be involved in the pathophysiology of mood disorders. Immunohistochemical staining of GAD 65/67 was performed in the orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex (DLPFC), the entorhinal cortex, the hippocampal formation and the medial dorsal and lateral dorsal (LD) thalamic nuclei, with a quantitative densitometric analysis of GAD-ir neuropil. The study was performed on paraffin-embedded brains from 9 unipolar and 12 bipolar I depressed patients (8 and 6 suicidal patients, respectively) and 18 matched controls. In unipolar patients, compared with controls, only the increased relative density of GAD-ir neuropil in the right LD was different from the previous results in depressed suicides from the same cohort (Gos et al. in J Affect Disord 113:45–55, 2009). On the other hand, the left DLPFC was the only area where a significant decrease was observed, specific for bipolar I depression. Significant differences between both diagnostic groups were found in these regions. By revealing abnormalities in the relative density of GAD-ir neuropil in brain structures, our study suggests a diathesis of the GABAergic system in mood disorders, which may differentiate the pathophysiology of unipolar from that of bipolar I depression.
Highlights
Abnormalities in the GABAergic system are assumed to play a crucial yet largely unknown role in the pathogenesis of mood disorders [3, 9, 41]
By revealing abnormalities in the relative density of Glutamic acid decarboxylase (GAD)-ir neuropil in brain structures, our study suggests a diathesis of the GABAergic system in mood disorders, which may differentiate the pathophysiology of unipolar from that of bipolar I depression
This impact was accentuated in our previous quantitative study on GAD-ir neuropil in the same cohort [21], where we found an increase in its density specific for depressed suicidal patients from the major depressive disorder (MDD) and bipolar disorder (BD) diagnostic groups
Summary
Abnormalities in the GABAergic system are assumed to play a crucial yet largely unknown role in the pathogenesis of mood disorders [3, 9, 41]. GAD is the rate-limiting enzyme involved in the conversion of glutamate to GABA with two isoforms, GAD 65 and GAD 67. Both of these functionally different isoforms are present in most GABA-containing neurones in the brain, but the transiently activated GAD 65 appears to be restricted to membranes and nerve endings, whereas the constitutively active GAD 67 is more widely distributed in cells [28, 42]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: European Archives of Psychiatry and Clinical Neuroscience
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
