Transdiagnostic symptom of depression and anxiety associated with reduced gray matter volume in prefrontal cortex

Dimensional models of psychopathology may provide insight into mechanisms underlying comorbid depression and anxiety and improve specificity and sensitivity of neuroanatomical findings. The present study is the first to examine neural structure alterations using the empirically derived Tri-level Model. Depression and anxiety symptoms of 269 young adults were assessed using the Tri-level Model dimensions: General Distress (transdiagnostic depression and anxiety symptoms), Anhedonia-Apprehension (relatively specific depression symptoms), and Fears (specific anxiety symptoms). Using structural MRI, gray matter volumes were extracted for emotion generation (amygdala, nucleus accumbens) and regulation (orbitofrontal, ventrolateral, and dorsolateral prefrontal cortex) regions, often implicated in depression and anxiety. Each Tri-level symptom was regressed onto each region of interest, separately, adjusting for relevant covariates. General Distress was significantly associated with smaller gray matter volumes in bilateral orbitofrontal cortex and ventrolateral prefrontal cortex, independent of Anhedonia-Apprehension and Fears symptom dimensions. These results suggests that prefrontal alterations are associated with transdiagnostic dysphoric mood common across depression and anxiety, rather than unique symptoms of these disorders. Additionally, no regions of interest were associated with Anhedonia-Apprehension or Fears, highlighting the importance of studying transdiagnostic features of depression and anxiety. This has implications for understanding mechanisms of and interventions for depression and anxiety.