title: Dysregulation of GABAergic neurotransmission in mood disorders: a postmortem study.
abstract: 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.
authors.affiliation: Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Otto-von-Guericke-University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. Hendrik.Bielau@Medizin.Uni-Magdeburg.de
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bielau
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Kurt
authors.initials: K
authors.lastname: Trübner
authors.forename: Ralf
authors.initials: R
authors.lastname: Brisch
authors.forename: Gabriela
authors.initials: G
authors.lastname: Meyer-Lotz
authors.forename: Michael
authors.initials: M
authors.lastname: Brodhun
authors.forename: Henrik
authors.initials: H
authors.lastname: Dobrowolny
authors.forename: Bruno
authors.initials: B
authors.lastname: Baumann
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gos
authors.forename: Hans-Gert
authors.initials: HG
authors.lastname: Bernstein
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bogerts
mesh_terms: D000368:Aged; D001714:Bipolar Disorder / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D005786:Gene Expression Regulation; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase