Reflex vasodilation and sweating in response to passive whole-body heating are blunted in women with major depressive disorder

Major depressive disorder (MDD) is associated with alterations in the mechanistic regulation of body temperature, including altered circadian temperature profiles, reduced sweating rates, and blunted cutaneous vasodilatory function. Interestingly, cutaneous vascular function appears preserved in adults with MDD treated with selective serotonin reuptake inhibitors (SSRIs), while serotonin norepinephrine reuptake inhibitors (SNRIs) may potentiate noradrenergic activity resulting in elevated blood pressure. Additionally, excessive sweating in thermoneutral conditions is a frequently reported side effect of common anti-depressant medications, like SSRIs and SNRIs; however, the effect of these medications on thermoregulatory function during passive heat stress have not been examined. Therefore, the purpose of this study was to measure reflex vasodilation and sweating responses to passive whole-body heat stress in women with MDD who are unmedicated or treated with SSRIs and SNRIs. Sixteen women with MDD (unmedicated; 18-36 yrs), 16 women with MDD treated with a SSRI (18-35 yrs), 16 women with MDD treated with a SNRI (19-36 yrs), and 16 non-depressed healthy women (19-36 yrs) were passively heated using a water-perfused suit until core temperature (Tc) increased by 1°C. Unmedicated women with MDD were experiencing a major depressive episode of mild-to-moderate severity measured by the Patient Health Questionnaire-9. Forearm blood flow (FBF; venous occlusion plethysmography) was measured at every 0.1°C increase in Tc, normalized to mean arterial pressure (MAP). Skin blood flow (SkBF; laser-Doppler flowmetry) and local sweat rate (LSR; ventilated sweat capsule) were continuously measured throughout passive heating. Forearm vascular conductance (FVC) during whole-body heating was reduced in both unmedicated women with MDD and SNRI-treated women compared to non-depressed and SSRI-treated women (all P< 0.0001). Greater increases in Tc from baseline were required to elicit increases in LSR in unmedicated women with MDD (Δ0.24 ± 0.17°C) compared to all other women [non-depressed: Δ0.07 ± 0.12°C; P=0.008; SSRI-treated: Δ0.04 ± 0.22°C; P=0.0002; SNRI-treated: Δ0.05 ± 0.22°C; P=0.003]. Similarly, greater increases in Tc from baseline were required to elicit increases in SkBF in unmedicated women with MDD (Δ0.18 ± 0.20°C) compared to all other women [non-depressed: Δ0.00 ± 0.09°C; P=0.007; SSRI-treated: Δ-0.03 ± 0.07°C; P=0.002; SNRI-treated: Δ0.03 ± 0.19°C; P=0.03]. Reflex vasodilation is blunted in unmedicated women with MDD and in women with MDD currently treated with a SNRI compared to both non-depressed and SSRI-treated women. Additionally, unmedicated women with MDD have a delayed onset of thermoregulatory effector function. Together, these data suggest that alterations in central control of thermoregulation are evident in unmedicated women with MDD; these detrimental effects are partially ameliorated by common antidepressant pharmacotherapies. Funding: NIH Grants T32 AG049676 (KGF and WLK) and R01 AG067471 (WLK) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.