Abstract
BACKGROUND AND AIMS: Gambling disorder (GD) patients continue to gamble despite negative consequences, and this behavior can be partly attributed to their insensitivity to failures and losses. GD may worsen over time and may stem from dysfunctions in the reward system and habenula, which encodes negative reward prediction errors. We aimed to elucidate habenular volume alterations that could intensify with illness duration and demonstrate heterogeneity in GD patients. METHODS: Sixty-eight male GD patients and 75 male healthy controls were included. We computed the habenular volume by deep learning-based auto-segmentation from T1-weighted MRI data and examined the between-group differences. We retrospectively calculated illness duration and evaluated the effects of illness duration, personality traits, and symptom severity on habenular volume in GD patients. RESULTS: GD patients showed comparable habenular volumes to those of healthy participants. After controlling for age, smoking status, IQ, and MRI scanner model, partial correlation analysis revealed a negative correlation between illness duration and habenular volume in GD patients (r = -0.26, p = 0.029). A significant correlation between habenular volume and illness duration appeared only in the severe subgroup (r = -0.42, p = 0.011). In the severe subgroup, higher neuroticism and lower conscientiousness were associated with larger habenular volume. DISCUSSION AND CONCLUSIONS: Habenular volume was negatively correlated with illness duration in GD patients, particularly in severe cases, and was influenced by symptom severity and personality traits. Habenular structural heterogeneity is based on severity and personality and possibly contributes to persistent gambling despite aversive consequences.