Elevated Plasma DISC1 Levels Are Associated With Motivational Deficits in Medication-Free Patients With Major Depressive Disorder: An Exploratory Study.

Disrupted-in-Schizophrenia 1 (DISC1) has been implicated in major psychiatric disorders, but the relationship between circulating DISC1 protein and dimensional motivation and pleasure-related features in major depressive disorder (MDD) is unknown. This exploratory cross-sectional study compared plasma DISC1 levels between 55 medication-free patients with MDD and 55 healthy controls (HCs) and examined associations with Clinical Assessment Interview for Negative Symptoms (CAINS) scores. Plasma DISC1 was measured by enzyme-linked immunosorbent assay, and the CAINS Motivation and Pleasure (MAP) and Expression (EXP) domains were assessed. Patients with MDD had higher CAINS-MAP, CAINS-EXP, and total scores; plasma DISC1 levels were nominally higher after covariate adjustment. In MDD, log10-transformed plasma DISC1 correlated with MAP and total CAINS after FDR correction, but not in HCs; Spearman sensitivity analyses yielded the same domain-specific pattern. These findings provide preliminary evidence of a modest association between plasma DISC1 and CAINS-MAP scores in medication-free patients with MDD.