Neurophysiological markers of GABAergic and glutamatergic function associated with childhood adversity in adolescent depression: An exploratory transcranial magnetic stimulation study.

We aimed to explore the relationships between childhood adversity, as assessed by the Childhood Trauma Questionnaire (CTQ) and transcranial magnetic stimulation (TMS) neurophysiological measures of GABAergic and glutamatergic neurotransmission. We hypothesized that elevated CTQ scores would have associations with dysregulated GABAergic and glutamatergic neurotransmission. Adolescents (N = 47) aged 12-18 years diagnosed with Major Depressive Disorder (MDD) were assessed with the CTQ and TMS neurophysiology measures (n = 40) including: Short-Interval Cortical Inhibition (SICI), Long-Interval Cortical Inhibition (LICI), the Cortical Silent Period (CSP), and Intracortical Facilitation (ICF). Spearman partial correlation coefficients, controlled for age, number of failed medical trials and depressive symptom severity were employed to examine potential associations among the CTQ and markers of GABAergic and glutamatergic neurotransmission. A significant positive correlation was observed between ICF-10 and physical abuse (ρ = 0.36276, p = 0.0297) suggesting an association with historical physical abuse and increased glutamatergic neurotransmission. Significant negative correlations also emerged between LICI-200 and emotional abuse (ρ = -0.36047, p = 0.0308), emotional neglect (ρ = -0.42310, p = 0.0101), physical neglect (ρ = -0.35610, p = 0.0330), and overall adversity scores (ρ = -0.515, p = 0.0013), suggesting that greater childhood adversity was associated with increased GABA-B mediated inhibitory neurotransmission. This study suggests that childhood adversity may be linked to distinct neurophysiological alterations in adolescents. These findings support the potential of TMS-derived measures as candidate biomarkers for adversity-related psychiatric disorders. Further studies should validate these findings in larger samples with a longitudinal design.