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Dysregulation of GABAergic Neurotransmission in Mood Disorders
Author(s) -
BIELAU HENDRIK,
STEINER JOHANN,
MAWRIN CHRISTIAN,
TRÜBNER KURT,
BRISCH RALF,
MEYERLOTZ GABRIELA,
BRODHUN MICHAEL,
DOBROWOLNY HENRIK,
BAUMANN BRUNO,
GOS TOMASZ,
BERNSTEIN HANSGERT,
BOGERTS BERNHARD
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1397.081
Subject(s) - dorsolateral prefrontal cortex , orbitofrontal cortex , hippocampus , gabaergic , prefrontal cortex , neuroscience , glutamate decarboxylase , temporal cortex , psychology , bipolar disorder , mood disorders , anterior cingulate cortex , medicine , endocrinology , psychiatry , biology , cognition , inhibitory postsynaptic potential , anxiety , biochemistry , enzyme
: Alterations of GABAergic neurotransmission are assumed to play a crucial role in the pathophysiology of mood disorders. Gamma‐aminobutyric acid (GABA) acts via binding to A and B receptors, whereas the B receptor is G protein‐coupled. Glutamic acid decarboxylase (GAD) is the key enzyme of GABA synthesis. Immunohistochemical staining of GAD 65/67‐immunoreactive neurons was performed in dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, superior temporal cortex, hippocampus formation, and mediodorsal thalamus with consecutive determination of neuronal density in 20 brains of patients with mood disorders (P) and 19 controls (C). In the patients' group were 11 patients with bipolar disorder (BD) and 9 patients with major depressive disorder (MDD). The data were tested statistically using analysis of variance (ANOVA) and post hoc Tukey tests. ANOVA revealed significant differences among the groups (C, BD, MDD) in dorsolateral prefrontal cortex, orbitofrontal cortex, superior temporal cortex, and hippocampus. Post hoc tests demonstrated higher neuronal densities in unipolar patients compared with bipolar patients and controls in dorsolateral prefrontal cortex, superior temporal cortex, and hippocampus. In the orbitofrontal cortex, a higher neuronal density was found in bipolar and unipolar patients compared with controls. In mood disorder patients, dose equivalents of antidepressants given prior to death correlated positively with the neuronal density in superior temporal cortex and hippocampus. The current data on GAD 65/67 point to a dysregulation of the GABAergic system in mood disorders. Possibly, existing deficits of GABAergic neurotransmission will be compensated or overcompensated by antidepressants. Additionally, albeit speculative, an imbalance between GABA production and transport might be of relevance.