Evaluation of brain structure and metabolism in currently depressed adults with a history of childhood trauma

Abstract

Structural differences in the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), hippocampus, and amygdala were reported in adults who experienced childhood trauma; however, it is unknown whether metabolic differences accompany these structural differences. This multimodal imaging study examined structural and metabolic correlates of childhood trauma in adults with major depressive disorder (MDD). Participants with MDD completed the Childhood Trauma Questionnaire (CTQ, n = 83, n = 54 female (65.1%), age: 30.4 ± 14.1) and simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI). Structure (volume, n = 80, and cortical thickness, n = 81) was quantified from MRI using Freesurfer. Metabolism (metabolic rate of glucose uptake) was quantified from dynamic ¹⁸F-fluorodeoxyglucose (FDG)-PET images (n = 70) using Patlak graphical analysis. A linear mixed model was utilized to examine the association between structural/metabolic variables and continuous childhood trauma measures while controlling for confounding factors. Bonferroni correction was applied. Amygdala volumes were significantly inversely correlated with continuous CTQ scores. Specifically, volumes were lower by 7.44 mm³ (95% confidence interval [CI]: -12.19, -2.68) per point increase in CTQ. No significant relationship was found between thickness/metabolism and CTQ score. While longitudinal studies are required to establish causation, this study provides insight into potential consequences of, and therefore potential therapeutic targets for, childhood trauma in the prevention of MDD. This work aims to reduce heterogeneity in MDD studies by quantifying neurobiological correlates of trauma within MDD. It further provides biological targets for future interventions aimed at preventing MDD following trauma. To our knowledge, this is the first simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) study to assess both structure and metabolism associated with childhood trauma in adults with MDD.

Fig. 1. Scatterplots of the residual values calculated from regional metabolism, thickness, and volume versus total Childhood Trauma Questionnaire (CTQ) score.

Residual values from multiple regression analysis of brain volume/thickness/metabolism covarying for age, age², and sex are displayed on the vertical axis. The colors represent the discrete categories of childhood trauma (none, low, moderate, severe) as defined in Table 1. The regression line represents the line of best fit. The lines surrounding the gray shaded area represent the 95% confidence interval. ACC Anterior Cingulate Cortex (A, E, G), AMY Amygdala (B, H), DLPFC Dorsolateral Prefrontal Cortex (C, F, I), HIP Hippocampus (D, J).

Fig. 2. Scatterplots of regional thickness in the cortical regions versus metabolism.

The regression line represents the line of best fit. The lines surrounding the gray shaded area represent the 95% confidence interval. DLPFC dorsolateral prefrontal cortex (A), ACC anterior cingulate cortex (B).