Differences between unipolar and bipolar I depression in the quantitative analysis of glutamic acid decarboxylase-immunoreactive neuropil

• Published in: European archives of psychiatry and clinical neuroscience 2012-12, Vol.262 (8), p.647-655
• Main Authors: Gos, Tomasz, Steiner, Johann, Bielau, Hendrik, Dobrowolny, Henrik, Günther, Karoline, Mawrin, Christian, Krzyżanowski, Maciej, Hauser, Roman, Brisch, Ralf, Bernstein, Hans-Gert, Jankowski, Zbigniew, Braun, Katharina, Bogerts, Bernhard
• Format: Article
• Language: English
• Subjects: Adult; Aged; Bipolar Disorder - drug therapy; Bipolar Disorder - pathology; Brain; Brain - drug effects; Brain - enzymology; Brain - pathology; Case-Control Studies; Cortex (cingulate); Cortex (entorhinal); Cortex (prefrontal); Depression; Depressive Disorder - drug therapy; Depressive Disorder - pathology; Enzymes; Female; gamma -Aminobutyric acid; Glutamate decarboxylase; Glutamate Decarboxylase - metabolism; Glutamic acid; Hippocampus; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Mood; Nervous system; neuropil; Neuropil - enzymology; Neuropil - pathology; Neurosciences; Neurotransmission; Original Paper; Psychiatry; Psychotropic Drugs - pharmacology; Psychotropic Drugs - therapeutic use; Statistics, Nonparametric; Suicide; Thalamic nuclei
• ISSN: 0940-1334; 1433-8491
• DOI: 10.1007/s00406-012-0315-x

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.