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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.


CONCLUSIONS
The study, revealing predominantly an increased relative density of GAD-ir neuropil, suggests the diathesis of GABAergic system specific for depressed suicidal patients.
Gos
Tomasz
T
Institute of Forensic Medicine, Medical University of Gdańsk, Poland. gost@amg.gda.pl
Günther
Karoline
K
Bielau
Hendrik
H
Dobrowolny
Henrik
H
Mawrin
Christian
C
Trübner
Kurt
K
Brisch
Ralf
R
Steiner
Johann
J
Bernstein
Hans-Gert
HG
Jankowski
Zbigniew
Z
Bogerts
Bernhard
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000033:anatomy & histology* / Q000201:enzymology* / Q000473:pathology; D003865:Major Depressive Disorder / Q000201:enzymology / Q000453:epidemiology / Q000523:psychology; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology; D019581:Neuropil / Q000378:metabolism*; D013405:Suicide / Q000523:psychology* / Q000706:statistics & numerical data*
D005968:Glutamate Decarboxylase