Anterior Cingulate Cortexγ-Aminobutyric Acid in Depressed Adolescents

Abstract

Context Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of γ-aminobutyric acid (GABA). Objective To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored. Design Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T. Setting Two clinical research divisions at 2 teaching hospitals. Participants Twenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12–19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age. Main Outcome Measures Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable. Results Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t= 3.2; P<.003). When subjects with MDD were categorized based on the presence of anhedonia, only anhedonic patients had decreased GABA/w levels compared with control subjects (t=4.08; P<.001; PTukey<.001). Anterior cingulate cortex GABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r = −0.50; P = .02), as well as for the entire participant sample including the control subjects (r=−0.54; P<.001). Anterior cingulate cortex white matter was also significantly decreased in adolescents with MDD compared with controls (P=.04). Conclusions These findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in the present study, may permit greater specificity in evaluating this important clinical feature.

Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression

“…Our search identified 45 studies: 26 studies for the comparison of patients with current MDE versus healthy controls, [8][9][10][11][12][13][14][15][16][17][18]30,[33][34][35][36][37][38][39][40][41][42][43][44][45][46] 12 studies for the comparison of patients with current MDE before treatment versus after treatment, 12,20,23,25,26,28,36,43,[47][48][49][50] and 11 for the comparison of euthymic patients and controls. 18,[21][22][23]27,29,38,[51][52][53][54] Figure 1 depicts the study selection proce...…”

“…For MRS studies, we calculated SMDs for the following regions of interest (ROIs) independently: the occipital cortex, [8][9][10][11][12]14,15,[20][21][22][23][24][25][26][27][28] the anterior cingulate cortex (ACC), 13,15,16,18,22 the dorsolateral prefrontal cortex (dlPFC), 29,30 the ventromedial prefrontal cortex (vmPFC) 29,30 and the left inferior frontal gyrus. 27 We estimated study heterogeneity using the Q statistic when SMDs were significant.…”

Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

“…Data processing and quantification procedures have been described (Gabbay et al, 2011;Geramita et al, 2011). Briefly, the 8-channel phased-array coil data recorded were combined into single regular time-domain free-induction decay signals, using a C-language computer program that implemented a previously published algorithm (Brown, 2004), with the unsuppressed voxel tissue water signal from each receiver coil element providing the required relative array coil sensitivities.…”

The role of anti-glutamic acid decarboxylase autoantibodies in mood disorders

“…[13] Significantly lower levels of GABA were observed in the anterior cingulate cortex (ACC) of adolescents with MDD compared with healthy subjects. [27] Levels were measured by the means of proton magnetic resonance spectroscopy and expressed as ratios to unsuppressed voxel tissue water (VTW). In this age group, significant differences were found for the ratio GABA/VTW in the ACC of adolescents with and without anhedonia but not in those nonanhedonic compared to healthy controls.…”

“…In this age group, significant differences were found for the ratio GABA/VTW in the ACC of adolescents with and without anhedonia but not in those nonanhedonic compared to healthy controls. [27] GABA PATHWAY-FOCUS ON GAD GABA is synthesized from GLU via decarboxylation by GAD, a pyridoxal phosphate-dependent enzyme. [28] Studies of GAD began in the early 50s with the work of Roberts and Frankel, [29,30] and Awapara [31] who independently discovered that GABA is synthesized in GABAergic neurons in CNS.…”