Brain Serotonin Transporter Remains Stable Across Seasons: A Bayesian and Frequentist Meta-Analysis

The "wintertime serotonin transporter (SERT) elevation hypothesis" is a foundational neurobiological model for seasonal affective disorder (SAD). Determining if normative wintertime SERT elevation is a genuine physiological rhythm or a pathological vulnerability is critical for developing targeted therapeutics. To quantitatively determine whether a significant seasonal variation in brain SERT availability exists in healthy individuals, a systematic search of Embase and Medline was conducted from inception to May 2026. Inclusion required observational neuroimaging studies comparing summer and winter SERT availability in healthy human subjects using positron emission tomography (PET) or single-photon emission computed tomography (SPECT). Of 54 initially identified articles, seven met the selection criteria. Standardized mean differences in SERT availability were synthesized utilizing both Bayesian hierarchical modeling and frequentist meta-analyses. The overall pooled effect size indicated no significant seasonal difference in SERT availability (0.11; 95% CI, -0.29 to 0.51). However, subgroup analyses revealed critical differences based on study design. Unpaired cross-sectional studies demonstrated a significant wintertime SERT increase, particularly in the brainstem and thalamus. In striking contrast, highly controlled paired longitudinal studies showed no significant seasonal variation overall (-0.26; 95% CI, -0.63 to 0.12; I²=0%) or regionally. Furthermore, meta-regression analyses confirmed that study design served as a significant moderator. In conclusion, brain SERT availability remains stable across seasons in healthy individuals, demonstrating robust homeostatic resilience. The variance in prior literature is overwhelmingly dictated by cross-sectional methodology. Therefore, wintertime SERT elevation likely represents a pathological vulnerability to SAD rather than a universal physiological rhythm.