Impulsive loss decision-making associated with aberrant meso-/habenular- cortical functional networks in young adults with major depressive disorder with suicidal ideation.

Abstract

Suicide, which involves a decision-making process biased toward a lethal option that may result in the loss of one's own life, remains a major public health concern, particularly among young adults with major depressive disorder (MDD). This study investigates whether impaired decision-making in the context of loss distinguishes young adults with MDD and suicidal ideation (MDSI) from those without suicidal ideation (MDNSI) and healthy controls (HC), and explores the underlying neurocomputational mechanisms. A total of 110 young adults (23 MDSI, 31 MDNSI, and 56 HC) underwent resting-state functional magnetic resonance imaging (fMRI) and completed a two-armed bandit decision-making task designed to separate loss and reward contexts. Accuracy and computational parameters reflecting decision impulsivity were compared among groups using analysis of covariance. Logistic regression was performed to identify features predicting MDSI among MDD patients. Response time modeling was conducted to differentiate loss-related impulsivity from indecisiveness. Functional connectivity analyses focused on the ventral tegmental area (VTA) and habenula networks to identify alterations mediating loss-decision impulsivity in MDSI. MDSI patients uniquely exhibited premature, value-insensitive impulsive decisions in the loss context, distinguishing them from MDNSI patients independent of depression severity. These decision abnormalities were not attributable to indecisiveness. In contrast, reward-based decision impairments were shared across both MDD subgroups. Disruptions in resting-state functional connectivity within the VTA-orbitofrontal and habenula-default mode networks in MDSI fully mediated their loss-specific impulsivity. These findings highlight loss-specific decision impulsivity and associated neural dysconnectivity as potential early markers of suicide risk, offering novel insights into targeted intervention strategies.