Abstract
OBJECTIVE: College students with subclinical depression often experience sleep disturbances and are at high risk of developing major depressive disorder without early intervention. Clinical guidelines recommend non-pharmacotherapy as the primary option for subclinical depression with comorbid sleep disorders (sDSDs). However, the neuroimaging mechanisms and therapeutic responses associated with these treatments are poorly understood. Additionally, the lack of an early diagnosis and therapeutic effectiveness prediction model hampers the clinical promotion and acceptance of non-pharmacological interventions for subclinical depression. METHODS: This study involved pre- and post-treatment resting-state functional Magnetic Resonance Imaging (rs-fMRI) and clinical data from a multicenter, single-blind, randomized clinical trial. The trial included 114 first-episode, drug-naïve university students with subclinical depression and comorbid sleep disorders (sDSDs; Mean age=22.8±2.3 years; 73.7% female) and 93 healthy controls (HCs; Mean age=22.2±1.7 years; 63.4% female). We examined altered functional connectivity (FC) and brain network connective mode related to subregions of Default Mode Network (sub-DMN) using seed-to-voxel analysis before and after six weeks of non-pharmacological antidepressant treatment. Additionally, we developed an individualized diagnosing and therapeutic effect predicting model to realize early recognition of subclinical depression and provide objective suggestions to select non-pharmacological therapy by using the newly proposed Hierarchical Functional Brain Network (HFBN) with advanced deep learning algorithms within the transformer framework. RESULTS: Neuroimaging responses to non-pharmacologic treatments are characterized by alterations in functional connectivity (FC) and shifts in brain network connectivity patterns, particularly within the sub-DMN. At baseline, significantly increased FC was observed between the sub-DMN and both Executive Control Network (ECN) and Dorsal Attention Network (DAN). Following six weeks of non-pharmacologic intervention, connectivity patterns primarily shifted within the sub-DMN and ECN, with a predominant decrease in FCs. The HFBN model demonstrated superior performance over traditional deep learning models, accurately predicting therapeutic outcomes and diagnosing subclinical depression, achieving cumulative scores of 80.47% for sleep quality prediction and 84.67% for depression prediction, along with an overall diagnostic accuracy of 82.34%. CONCLUSIONS: Two-scale neuroimaging signatures related to the sub-DMN underlying the antidepressant mechanisms of non-pharmacological treatments for subclinical depression. The HFBN model exhibited supreme capability in early diagnosing and predicting non-pharmacological treatment outcomes for subclinical depression, thereby promoting objective clinical psychological treatment decision-making.