Gray Matter Volume Predicts Improvement in Depression Symptoms Following Psychotherapy in Late Life Depression

Many individuals with Late Life Depression fail to respond to psychotherapy treatment. Understanding what factors affect treatment response is a critical step toward improving geriatric mental health care. The authors examined associations between baseline regional gray matter volume and depression symptom improvement following a structured psychotherapy intervention.

Longitudinal observational study with pre- and post-intervention assessment.

Outpatient clinical research setting.

Older adults with major depression (N = 104, ages 65-91).

Problem Solving Therapy.

Structural Magnetic Resonance Imaging was acquired at baseline. Depression severity was evaluated at baseline and post-intervention. Logistic regression evaluated whether a composite score of gray matter regions encompassing affective and cognitive networks at baseline was associated with treatment response, controlling for age, sex, education, baseline depression severity, and intracranial volume. Exploratory logistic regression analyses evaluated associations between individual gray matter regions and treatment response.

Greater composite gray matter volume at baseline was associated with a greater likelihood of significant depression symptom improvement (z = 2.05, OR = 2.27, p = 0.040). Exploratory analyses identified greater bilateral posterior cingulate cortex, left insula, left precuneus, left rostral anterior cingulate cortex, and right nucleus accumbens as significantly associated with better treatment response.

Greater gray matter volume prior to therapy is associated with a greater likelihood of depression symptom improvement following psychotherapy. While several regions overlap with those shown to predict antidepressant treatment response (posterior cingulate cortex, precuneus, insula, and anterior cingulate cortex), others diverge (nucleus accumbens). Future work should evaluate nucleus accumbens volume as a potential biomarker of psychotherapy treatment response.