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Eur Arch Psychiatry Clin Neurosci (2012) 262:647655 DOI 10.1007/s00406-012-0315-x
ORIGINAL PAPER
Differences between unipolar and bipolar I depression in the quantitative analysis of glutamic acid decarboxylase-immunoreactive neuropil
Tomasz Gos Johann Steiner Hendrik Bielau Henrik Dobrowolny Karoline Gnther
Christian Mawrin Maciej Krzy_
zanowski Roman Hauser Ralf Brisch Hans-Gert Bernstein
Zbigniew Jankowski Katharina Braun Bernhard Bogerts
Received: 12 October 2011 / Accepted: 27 March 2012 / Published online: 13 April 2012 The Author(s) 2012. This article is published with open access at Springerlink.com
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. Immunohisto-chemical 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 parafn-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 113:4555, 2009). On the other hand, the left DLPFC was the only area where a signicant decrease was observed, specic for bipolar I depression. Signicant 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.
Keywords GAD 65/67 Postmortem Depression
Unipolarbipolar dichotomy
Introduction
Abnormalities in the GABAergic system are assumed to play a crucial yet largely unknown role in the pathogenesis of mood disorders [3, 9, 41]. Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the mature brain and plays an important role in synchronised neural network oscillations [17],...