Psychol Med. 2025 Nov 28;55:e363. doi: 10.1017/S0033291725102638.
ABSTRACT
BACKGROUND: Psychomotor disturbance has long been observed in major depressive disorder (MDD) and is thought to be a key indicator of illness course. However, dominant methods of measuring psychomotor disturbance, via self-report and clinician ratings, often lack objectivity and may be less sensitive to subtle psychomotor disturbances. Furthermore, the neural mechanisms of psychomotor disturbance in MDD remain unclear.
METHODS: To address these gaps, we measured psychomotor agitation via a force variability paradigm and collected resting fMRI in 47 individuals with current MDD (cMDD) and 93 individuals with remitted MDD (rMDD). We then characterized whether resting-state cortico-cortical and cortico-subcortical connectivity related to force variability and depressive symptoms.
RESULTS: Behaviorally, individuals with cMDD exhibited greater force variability than rMDD individuals (t(138) = 3.01, p = 0.003, Cohen’s d = 0.25). Furthermore, greater force variability was associated with less visuomotor connectivity (r(130) = -0.23, p = 0.009, 95% CI [-0.38, -0.06]). Visuomotor connectivity was significantly reduced in cMDD relative to rMDD (t(130) = -2.77, p = 0.006, Cohen’s d = -0.24) and mediated the group difference in force variability (ACME β = -0.06, 95% CI [-0.16, -0.01], p = 0.04).
CONCLUSIONS: Our findings represent a crucial step toward clarifying the pathophysiology of psychomotor agitation in MDD. Specifically, altered visuomotor functional connectivity emerged as a candidate neural mechanism, highlighting a promising direction for future research on dysfunctional visually guided movements in MDD.
PMID:41310957 | DOI:10.1017/S0033291725102638
