Front Psychiatry. 2026 Aug 3;17:1921655. doi: 10.3389/fpsyt.2026.1921655. eCollection 2026.
ABSTRACT
Seasonal affective disorder (SAD) and bipolar disorder (BD) with a seasonal pattern are conventionally framed as disorders of photoperiod and circadian timing, yet affected individuals also show a striking, reproducible metabolic rhythm-carbohydrate craving and weight gain in winter, appetite reduction and weight loss in summer-that has rarely been integrated into mechanistic models of seasonal mood cycling. Building on an evolutionary “metabolic plasticity” view, in which seasonal shifts in energy storage are conserved adaptations that can become maladaptive in predisposed individuals, we propose the Seasonal Metabolic Oscillation (SMO) hypothesis: that the seasonal expansion and contraction of adipose tissue is not merely a passive symptom but a candidate mediator and amplifier of seasonal mood cycling. We advance two claims of deliberately unequal evidentiary strength. The better-supported core claim is that winter adiposity amplifies and helps maintain the depressive phase, by promoting low-grade neuroinflammation and indoleamine 2,3-dioxygenase (IDO1) activation, which diverts tryptophan into the kynurenine pathway, and by adding leptin resistance and stress-axis dysregulation that together bias the brain toward depression. The more tentative, exploratory claim is that the spontaneous loss of adiposity in summer relieves this inflammatory burden and, through photoperiod-driven changes in dopaminergic and circadian signaling, may lower the threshold for mood elevation in predisposed individuals. Pleiotropic circadian and metabolic variants, including ZBTB20 and NPAS2, are proposed to confer joint vulnerability to SAD, obesity, and bipolar spectrum illness. The model yields a central, falsifiable prediction-that within the same individuals seasonal swings in adiposity statistically precede and account for a defined share of seasonal mood change-and is directly testable through weight-stabilization experimental-medicine trials, within-subject longitudinal biomarker tracking, and Mendelian randomization. We stress that the model’s two central assumptions-that seasonal adiposity change temporally precedes mood change, and that a swing of the modest magnitude typical of SAD is quantitatively sufficient to move central neurochemistry-remain experimentally undemonstrated, and that photoperiod is a plausible common cause of both adiposity and mood that only designs decoupling the two can exclude. If supported, SMO would reframe seasonal mood disorders as recurrent metabolic-neuroimmune-mood conditions and motivate metabolically informed screening, pharmacotherapy, and chronotherapy.
PMID:42609474 | PMC:PMC13478500 | DOI:10.3389/fpsyt.2026.1921655
