Major depressive disorder with preserved sexual interest represents a distinct subtype: results from resting-state fMRI.

INTRODUCTION: Sexual-interest symptoms are common in major depressive disorder (MDD), yet their neurodynamic correlates remain unclear. This study examined whether 17-item Hamilton Depression Rating Scale (HAMD-17) Item-14 sexual-interest symptom status in MDD is associated with variation in resting-state brain co-fluctuation dynamics. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were obtained from MDD patients with HAMD-17 Item-14 sexual-interest symptoms (SI+, n = 111), MDD patients without such symptoms (SI-, n = 110), and healthy controls (HC, n = 203). Edge-time series (ETS) were computed as the element-wise products of z-scored blood-oxygen-level-dependent signals between pairs of brain regions. The co-fluctuation strength of each ETS was quantified at each frame using the root sum square (RSS), and frames were categorized into high (top 5%), intermediate (normal 90%), and low (bottom 5%) amplitude states to characterize global co-fluctuation amplitude, temporal persistence, and transition dynamics. Principal component analysis (PCA) was further applied to high-amplitude frames to examine default mode network (DMN)-related co-fluctuation patterns. RESULTS: The clearest subgroup differences were observed in intermediate-amplitude co-fluctuation and trough-to-trough duration. Relative to SI-, SI+ showed higher intermediate-amplitude RSS, shorter duration, and less persistent transition dynamics, suggesting heightened but more temporally unstable resting-state coordination. During high-amplitude events, PCA identified an antagonistic mode between the somatomotor/ventral attention networks and the DMN, with DMN-related differences most evident between SI+ and HC. CONCLUSIONS: 17-item Hamilton Depression Rating Scale Item-14 sexual-interest symptom status in MDD was associated with altered resting-state co-fluctuation dynamics, with DMN-related differences most evident relative to healthy controls. These findings suggest that this routinely assessed symptom marker may help identify clinically relevant heterogeneity within MDD and may support greater clinical attention to symptom dimensions potentially relevant to treatment adherence and patient-reported outcomes. However, the findings should be interpreted as non-specific resting-state correlates of an Item-14-defined clinical profile, rather than as direct neural indices of sexual interest or as a basis for mechanistic or treatment guidance. Further studies using detailed sexual-function assessments and longitudinal or multimodal designs are needed to clarify the specificity and clinical relevance of these associations.