Out-of-distribution evaluation showed broadly similar patterns, supporting the promise of multimodal AI for predicting RBD in MDD and identifying interpretable potential digital markers of prodromal synucleinopathy.
Abstract
REM sleep behavior disorder (RBD) is a robust prodromal marker of α-synucleinopathies: idiopathic RBD carries a 10-15-year phenoconversion risk of 80-90% to Parkinson's disease (PD) and related disorders. In major depressive disorder (MDD), comorbid RBD marks a subgroup at elevated prodromal PD risk, yet is frequently missed in psychiatric practice. Here, we developed a multimodal AI framework to detect comorbid RBD in MDD. From a clinical cohort of 329 patients, we obtained 261 video clips in 31 patients during reading and spontaneous-speech tasks, including 19 patients with MDD-RBD and 12 demographically and medication-matched MDD-only controls that, to our knowledge, formed the largest cohort of its kind worldwide. We used a dual-stream multimodal model that learned facial dynamics from video and vocal features from speech, and then combined both signals to predict comorbid RBD. In 5-fold cross-validation, our best model achieved 80.5% accuracy and 0.848 F1-score. Explainability analysis highlighted lower-face tension and variability, together with brow lowering, as candidate biomarkers requiring further validation. Predicted risk correlated with RBDQ score (r = 0.53, p = 0.005) and weakly with UPDRS motor score (r = 0.34, p = 0.067). Out-of-distribution evaluation showed broadly similar patterns, supporting the promise of multimodal AI for predicting RBD in MDD and identifying interpretable potential digital markers of prodromal synucleinopathy.
Gut microbiome provides a candidate approach for potential risk stratification in psychiatric populations, and MDD + RBD may represent a biologically distinct depression subtype associated with potential neurodegenerative risk.
Yuhua Yang, Ningning Li, Li Zhou et al.· Molecular Psychiatry· 0 citations
Improved MDD-recurrence understanding is aimed at by studying these four selected perspectives in combination and prospectively during remission by studying different predictors of recurrence in combination.
Background: Essential Tremor (ET) has traditionally been regarded as a pure motor disorder. However, emerging evidence suggests associations with non-motor symptoms, including cognitive impairment, psychiatric disturbances, and sleep abnormalities. REM Sleep Behavior Disorder (RBD) is a known prodromal feature of alpha-synucleinopathies such as Parkinson’s disease (PD). The relationship between ET and RBD remains unclear, with previous studies reporting variable prevalence rates. Objective: This study aimed to determine the prevalence of probable RBD (pRBD) among patients with ET using the REM Sleep Behavior Disorder Single-Question Screen (RBD1Q). Methods: In this single-center, cross-sectional study, we identified ET patients from the Parkinson’s Disease Center and Movement Disorders Clinic at Baylor College of Medicine. Eligible patients were contacted and screened for pRBD using the RBD1Q. A small cohort of healthy controls, including spouses, was also screened. Demographic and clinical characteristics were compared between ET patients with and without pRBD. Results: Among 245 ET patients, 21.2% screened positive for pRBD. There were no significant differences in age, age at tremor onset, or tremor duration between patients with and without pRBD. There was a significantly higher percentage of males among ET patients with pRBD (63.5% vs. 48.7%, p = 0.045). Discussion: In this study, pRBD screen positivity was relatively more common in ET patients than historical controls. These findings suggest that sleep-related symptoms may be relevant in ET and support further study with polysomnographic confirmation of RBD and longitudinal follow-up of these symptoms in ET patients.
P. Petramfar, Steven Bellows· Tremor and Other Hyperkineti...· 0 citations
Major Depressive Disorder (MDD) is a prevalent and disabling psychiatric disorder. Its clinical heterogeneity undermines diagnostic precision and treatment effectiveness. While DSM-5 defines melancholic and anxious subtypes based on symptoms, their neurophysiological bases remain unclear. Resting-state electroencephalography (EEG) provides a non-invasive approach for investigating neurophysiological heterogeneity in depression. Beta-band oscillations are associated with reward processing, motivation, and cortical arousal, which may differ across subtypes.
We analyzed 325 patients with MDD, classified into melancholic (
n
= 108), anxious (
n
= 102), and non-melancholic and non-anxious (
n
= 115) groups. Relative spectral power and phase-locking value (PLV) in beta1 (12–20 Hz) and beta2 (20–30 Hz) bands were compared. Logistic regression and subtype-specific correlation analyses assessed classification and clinical associations.
Melancholic depression was associated with widespread reductions in beta2 power and higher suicide risk, whereas anxious depression showed altered beta-band functional connectivity, particularly involving left temporal-region connections. Both subtypes shared reduced prefrontal–temporal connectivity. Exploratory classification analyses showed modest discriminative performance after leakage-controlled cross-validation. Associations between beta1 activity and symptom severity were observed only in the anxious subtype.
Melancholic and anxious depression showed partially distinct beta-band EEG patterns. These findings provide preliminary evidence that beta-band EEG features may capture subtype-related neurophysiological heterogeneity in MDD, with subtype-specific associations between neural activity and symptom severity. Further validation is required before these features can be considered clinically applicable.
The trial was registered at the Chinese Clinical Trial Registry on 04/23/2022 ( www.chictr.org.cn ChiCTRID ChiCTR2200059053).
Mengyuan Cheng, Ziyao Su, Haoran Zhang et al.· BMC Psychiatry· 0 citations
This study aimed to develop and evaluate a spatiotemporal deep-neural-network (stDNN) using resting-state fMRI (rs-fMRI) data to identify brain biomarkers associated with isolated REM sleep behavior disorder (iRBD) and Parkinson's disease (PD) and to differentiate these conditions from controls. The final sample included 771 subjects, comprising 423 patients with PD, 144 with iRBD, and 204 healthy controls. stDNN model was applied to mean timeseries extracted for each subject from rs-fMRI data. By integrating spatio-temporal features, the network classified subjects based on distinct neural patterns. Model generalizability was assessed using subject-wise k-fold cross-validation. Explainable artificial intelligence (XAI) methods were applied. stDNN achieved balanced accuracy rates of 71.0% in distinguishing controls from PD and up to 71.9% in middle-stage PD cases. It also demonstrated over 80% accuracy in differentiating healthy controls from iRBD. XAI analysis highlighted the involvement of fronto-parietal and temporal regions, including the dorsolateral prefrontal cortex, and anterior temporal gyri, in distinguishing controls from PD. In the comparison with iRBD, key contributing areas included the bilateral superior and medial frontal gyri, dorsolateral prefrontal cortex, parietal and occipital regions (lingual gyri and cuneus). This study demonstrates the potential of stDNN to differentiate between iRBD, PD, and controls using rs-fMRI data.
S. Basaia, S. Pisano, E. Sarasso et al.· npj Parkinson's Disease· 0 citations
OBJECTIVE
First-episode, drug-naïve (FEDN) patients with major depressive disorder (MDD) frequently exhibit disturbances in stress perception and cognitive function, yet the neural correlates remain unclear. This study investigated associations of altered regional homogeneity (ReHo) in the right precuneus with subjective stress perception in FEDN MDD.
METHODS
We enrolled 139 FEDN patients and 65 healthy controls. Propensity score matching (PSM) balanced age, sex, and head motion, yielding 63 pairs. Resting-state fMRI was acquired and preprocessed; whole-brain ReHo maps were computed. Voxel-wise group comparison with GRF correction identified decreased ReHo in the right precuneus, which was defined as the region of interest. Within patients, partial correlations between right precuneus ReHo and Perceived Stress Scale (PSS) total, helplessness, and self-efficacy scores were examined, controlling for age, sex, mean framewise displacement, HAMD-17, and HAMA.
RESULTS
Compared to controls, FEDN patients showed significantly decreased right precuneus ReHo. In patients, after controlling for age, sex, mean framewise displacement, HAMD-17 score, and HAMA score, right precuneus ReHo was negatively associated with the self-efficacy dimension of the PSS (r = -0.497, p = 0.011). A nominal positive association was also observed between right precuneus ReHo and the PSS total score (r = 0.399, p = 0.048), whereas no significant association was found with helplessness.
CONCLUSION
Altered right precuneus spontaneous activity was associated with perceived stress-related cognitive appraisal, particularly stress-coping self-efficacy, in FEDN patients with MDD after controlling for depressive and anxiety symptom severity. These findings highlight a potential role of the right precuneus in stress-coping self-efficacy in FEDN MDD patients.
Ning Yang, Jianan Zhou, Yuanyuan Liu et al.· Journal of Affective Disorde...· 0 citations
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