Abstract
BACKGROUND: Bright light therapy (BLT) demonstrates efficacy in alleviating subthreshold depression (StD) among young adults. The amygdala plays a critical role in depression. METHODS: StD subjects were divided into BLT group (N=47) and placebo group (N=42). Depression severity was assessed using HAM-D, Centre for Epidemiologic Studies Depression Scale (CES-D) and Beck Depression Inventory (BDI) pre-/post-8-week intervention. Structural/resting-state fMRI scan was conducted. Seed-based static FC (sFC) and dynamic FC (dFC) analyses of the bilateral amygdala and their subfields were conducted. RESULTS: Compared to placebo, BLT showed reduced depression scale, and increased sFC of right basolateral amygdala (BLA)/superficial amygdala (SFA)-right middle temporal gyrus (MTG) and dFC of right centralmedial amygdala (CMA) and right inferior orbital frontal gyrus, and decreased sFC of right amygdalostriatal transition/CMA- left thalamus and dFC of right SFA- right medial prefrontal cortex after intervention; while the whole amygdala and its subnuclei volume did not change significantly after BLT. Right BLA-MTG sFC changes positively correlated with BDI improvement. Baseline amygdala sFC/dFC predicted post-BLT symptom changes. BLT-induced right BLA sFC alterations spatially correlated with 5-HT1A/5-HT2A receptor distributions, and right CMA dFC changes with 5-HT1A. CONCLUSIONS: Findings suggest BLT modulates amygdala-thalamocortical circuits and serotonergic pathways, highlighting FC biomarkers for treatment efficacy assessment. TRIAL REGISTRATION CLINICALTRIALS.GOV IDENTIFIER: ChiCTR2000032633.