Bright light therapy induces insular frequency-specific functional plasticity in young adults with subthreshold depression: A randomized, double-blind, placebocontrolled study

Bright light therapy has demonstrated efficacy in treating depression, and the insula is implicated in depressive disorders. However, the role of insular neural circuit alterations in mediating the efficacy of bright light therapy for depression remains unclear. Here, we aimed to investigate the relationship between depressive symptom improvement and insular functional connectivity changes following bright light therapy in individuals with subthreshold depression. In this randomized controlled trial, 89 individuals diagnosed with subthreshold depression were allocated to either 8-week bright light therapy (n = 47) or placebo control (n = 42). All participants completed the Hamilton Depression Rating Scale and Center for Epidemiologic Studies Depression Scale and underwent resting-state functional magnetic resonance imaging pre- and post-intervention. Seed-based whole-brain functional connectivity analysis examined insular connectivity across distinct frequency bands (routine, slow-4, and slow-5). Bright light therapy significantly reduced depressive symptoms. The following frequency-specific functional connectivity changes were observed: i) increased left ventral anterior insula-right middle frontal gyrus connectivity in the routine band; ii) decreased left dorsal anterior insula-left putamen and bilateral ventral anterior insula-left putamen connectivity in the slow-4 band; and iii) decreased left dorsal anterior insula- right cerebellar anterior lobe and increased left posterior insula-middle temporal gyrus connectivity in the slow-5 band. Notably, reduced left dorsal anterior insula-right cerebellar anterior lobe functional connectivity was correlated with symptom improvement. These findings suggest that bright light therapy might alleviate depressive symptoms through insular circuit plasticity, thereby providing novel insights into its neurobiological mechanisms in subthreshold depression (Chinese Clinical Trial Registry Identifier: ChiCTR2000032633).