5.31 ANTERIOR CINGULATE CORTEX GAMMA-AMINOBUTYRIC ACID IN DEPRESSED ADOLESCENTS: A RELATIONSHIP TO ANHEDONIA

• Published in: Journal of the American Academy of Child and Adolescent Psychiatry Vol. 55; no. 10; pp. S193 - S194
• Main Authors: Ostrover, Reynolds, BA, Freed, Rachel D., PhD, Stadterman, Jill, BA, Case, Julia A., BA, Gabbay, Vilma, MD
• Format: Journal Article
• Language: English
• Published: Baltimore Elsevier Inc 01.10.2016; Elsevier BV
• Subjects: Adolescents; Anhedonia; Child & adolescent psychiatry; Children; Control Groups; Correlation; Cortex; Cortex (cingulate); Depression; Depression (Psychology); Drugs; Gamma-aminobutyric acid; Hedonic response; Medical screening; Mental depression; Morbidity; Neuroimaging; Neuropsychology; Neurotransmitters; Pathophysiology; Pediatrics; Physiological psychology; Psychiatry; Psychotropic drugs; Quantitative psychology; Rating Scales; Review boards; Severity; Suicide; Water; γ-Aminobutyric acid
• ISSN: 0890-8567; 1527-5418
• DOI: 10.1016/j.jaac.2016.09.290

Objectives: Adolescent MDD is a devastating condition, associated with significant morbidity and suicide risk. Nonetheless, its pathophysiology remains poorly understood. Addressing the disorder's heterogeneity and the inability to replicate biological findings, there has been a shift to examine specific behavioral constructs rather than categorical diagnoses. In our prior work, we documented that anhedonia, a core symptom of MDD, is highly variable among depressed adolescents. Additionally, in a neuroimaging study, we found a reduction of anterior cingulate cortex (ACC) GABA, the major inhibitory neurotransmitter, in youth with MDD; we further showed that this reduction was driven by the clinical symptomology of anhedonia. Here we sought to replicate these findings in a larger sample. Methods: The study was approved by Institutional Review Boards at NYU and Mount Sinai, from where participants were recruited, and Weill Cornell Medical Center, where scanning procedures were carried out. We enrolled 48 psychotropic medication-free youth with MDD and 36 healthy controls (HC), ages 12-21. Subjects were evaluated using the K-SADS. MDD subjects had episode durations >= 8 weeks and Children's Depression Rating Scale (CDRSR) severity scores >= 38. Anhedonia severity was captured using a sum of responses to anhedonia items on the CDRSR and Beck Depression Inventory. GABA levels in the ACC were measured using 1H-MRS, and expressed as ratios relative to unsuppressed ACC voxel tissue water (w), GABA/w. Results: Mean ACC GABA/w levels in youth with MDD were significantly decreased compared to those in HC (t = 2.56, p = .01). Additionally, we found a negative correlation between anhedonia and ACC GABA/w levels in both the entire sample (rho = -.36, p < .01) and in the MDD group alone (rho = -.34, p = .03). Conclusions: As hypothesized, ACC GABA levels were lower in adolescents with MDD compared to HC. Lower GABA in this region was also associated with greater anhedonia severity. These findings confirm the results of our previous work and add to the literature on the relationship between ACC GABA and anhedonia. This study will help to inform the development of future preventative interventions and treatments.