Background: Depression has been associated with a decrease in intracellular serotonin (5-HT) reuptake through its transporter, SERT. The 5-HT transporter long promoter region (5-HTTLPR) deletion in the SERT gene has also been associated with a decrease in 5-HT reuptake. Conversely, increases in extracellular 5-HT have been associated with increased temperature. It has not been established, however, whether body temperature in depressed patients is different from controls. Here, we hypothesized that temperature would be increased in depressed patients as well as in those with the 5-HTTLPR deletion. Methods: A strict oral temperature protocol employed single, cross-sectional, naturalistic time-of-day temperature measures in 125 subjects (46 normal controls, 79 outpatients with major depression). Controls and depressed patients were free of psychotropic medication and classified by the Structured Clinical Interview for Psychiatric Diagnoses. Eighty-one of the subjects (68 depressed, 13 normal) were additionally genotyped for 5-HTTLPR polymorphisms. Results: Depressed patients had a significantly higher uncorrected body temperature (mean ± SD 98.38 ± 0.61°F) than controls (mean ± SD 98.13 ± 0.59°F; F = 4.8, p = 0.03). An age (F = 14.09, p < 0.001) and time-of-day (11.4, p = 0.001) correction revealed a more robust (F = 14.02, p < 0.001) difference between depressed patients (mean ± SD 98.44 ± 0.55°F) and controls (mean ± SD 98.02 ± 0.56°F). When normalized for age and circadian differences between subjects, random, outpatient oral temperatures had a sensitivity of 63% and a specificity of 76% in identifying the depressed subjects from the controls. Independent of depression, subjects with the 5-HTTLPR deletion (short SERT allele) were warmer (mean ± SD 98.33 ± 0.65°F) than those lacking the short allele on either chromosome (mean ± SD 97.91 ± 0.69°F; F = 7.0, p = 0.01). However, the genotype did not explain the temperature differences between controls and depressed patients. Conclusion: This is the first demonstration of an increased daytime body temperature in cases with major depression. Subjects with a corrected temperature above 98.3°F were 2.6-fold more likely to be depressed. The results may strengthen the hypothesis of an inflammatory component of depression. In addition, the findings suggest a potential link between genetic differences in 5-HT transport and body temperature.

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