Article

Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-Immunoreactive neuropil

Institute of Forensic Medicine, Medical University of Gdańsk, Poland.
Journal of Affective Disorders (Impact Factor: 3.38). 07/2008; 113(1-2):45-55. DOI: 10.1016/j.jad.2008.04.021
Source: PubMed

ABSTRACT

Alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Glutamic acid decarboxylase (GAD) is the key enzyme of GABA synthesis.
Immunohistochemical staining of GAD 65/67 was performed in the orbitofrontal, anterior cingulate and dorsolateral prefrontal cortex (DLC), the entorhinal cortex (EC), the hippocampal formation, and the medial dorsal and lateral dorsal thalamic nuclei, with consecutive determination of GAD-immunoreactive (-ir) neuropil relative density. The study was performed on paraffin-embedded brains from 21 depressed patients (14 of whom had committed suicide) and 18 matched controls. The data were tested using Kruskal-Wallis, Mann-Whitney (U) and Spearman statistical procedures.
As shown by post-hoc U-tests, an increase in the relative density of GAD-ir neuropil was present in the hippocampal formation, specific for suicidal patients. The EC was the only area where non-suicidal patients also revealed an increase compared with controls. On the contrary, the DLC was the only area where a significant decrease existed, specific for non-suicidal patients. Numerous negative correlations were found between the investigated parameter and psychotropic medication.
A major limitation of this study is the relatively small case number. A further limitation is given by the lack of data on drug exposure across the whole life span. The possible impact of unipolar-bipolar dichotomy of mood disorders on the obtained results should also be considered.
The study, revealing predominantly an increased relative density of GAD-ir neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients.

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    • "AD67 , GAD65 , parvalbumin , and calbindin levels in certain brain regions , including the hippocampus and cerebral cortex ( Levav - Rabkin et al . , 2010 ) . Increased density of GAD65 / 67 - immunoreactive neuropil suggests a GABAergic hyperactivity in the hippocampus and might compose a risk factor for suicidal behavior in affective disorders ( Gos et al . , 2009 ) . Increased densities of GAD65 / 67 - positive neurons in the dorsolateral prefrontal and superior temporal cortices and in the hippocampus have been observed among patients with major depressive disorder compared with control subjects and patients with bipolar disorder as well as in the orbitofrontal cortex among patients with major "
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    • "A quantitative morphological analysis was performed in each of the selected sections as reported previously [21]. The relative density of GAD-ir neuropil (the quotient of the area of fibres and/or synaptic endings and total measuring field area, see below) of depressed patients and controls was measured in neocortical areas: prefrontal [DLPFC, orbitofrontal (OFC) and pregenual anterior cingulate] and temporal [parahippocampal gyrus containing the entorhinal cortex (EC)], in the hippocampal formation [dentate gyrus (DG) and the CA1 field of the hippocampus (CA1)] and in thalamic nuclei (medial dorsal [MD] and LD). "
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    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.
    Full-text · Article · Apr 2012 · European Archives of Psychiatry and Clinical Neuroscience
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    • "Therefore, it is likely that reduced GAD-67 immunoreactivity in the dorsolateral PFC is due to a reduction in the density and size of calbindin-positive somata of GABAergic interneurons. Other postmortem studies investigating GAD in depression found reductions in GAD-65/67 immunopositive structures in the dorsolateral PFC (Gos et al., 2008) and in GAD protein level in the cerebellum (Fatemi et al., 2005). "
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