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

ABSTRACT 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, log 10 ‐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.