Increased Seasonal Variation in Serotonin Transporter Binding in Seasonal Affective Disorder

Abstract

Seasonal affective disorder (SAD) is highly prevalent with rates of 1-6% and greater prevalence at more extreme latitudes; however, there are almost no direct brain investigations of this disorder. In health, serotonin transporter binding potential (5-HTT BPND), an index of 5-HTT levels, is greater throughout the brain in fall-winter compared with spring-summer. We hypothesized that in SAD, this seasonal variation would be greater in brain regions containing structures that regulate affect such as the prefrontal and anterior cingulate cortices (PFC and ACC). Furthermore, given the dimensional nature of SAD symptoms, it was hypothesized that seasonal fluctuation of 5-HTT BPND in the PFC and ACC would be greatest in severe SAD. Twenty SAD and twenty healthy participants underwent [(11)C]DASB positron emission tomography scans in summer and winter to measure seasonal variation in [(11)C]DASB 5-HTT BPND. Seasonal increases in [(11)C]DASB 5-HTT BPND were greater in SAD compared with healthy in the PFC and ACC, primarily due to differences between severe SAD and healthy (severe SAD vs healthy; Mann-Whitney U, U=42.5 and 37.0, p=0.005 and 0.003, respectively; greater magnitude in severe SAD of 35.10 and 14.23%, respectively), with similar findings observed in other regions (U=40.0-62.0, p=0.004-0.048; greater magnitude in severe SAD of 13.16-17.49%). To our knowledge, this is the first brain biomarker identified in SAD. This creates a new opportunity for phase 0 studies to target this phenotype and optimize novel prevention/treatment strategies for SAD.

Figure 1

Seasonal percent change in serotonin transporter binding potential (% Δ 5-HTT BP_ND) as measured in eight brain regions of interest (ROIs). Open (healthy, n=20) and grey (moderate SAD, n=9) and black (severe SAD, n=11) triangles represent individual subject % Δ 5-HTT BP_ND. Black bars represent mean % Δ 5-HTT BP_ND for each group. % Δ 5-HTT BP_ND was significantly greater in the prefrontal and anterior cingulate cortices (severe SAD vs healthy; Mann–Whitney U, U=42.5 and 37.0, p=0.005 and 0.003, respectively; greater magnitude in severe SAD of 35.10% and 14.23%, respectively) with similar findings observed in other regions (U=40.0–62.0, p=0.004–0.048; greater magnitude in severe SAD of 13.16–17.49%). To compare groups, the Kruskal–Wallis H-test was also applied at each region of interest. ^ap-value⩽0.005; ^bp-value⩽0.01; ^cp-value⩽0.05. Seasonal % Δ 5-HTT BP_ND was consistent within individuals across brain regions (Cronbach's alpha, α=0.89).