Abstract

Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute to well-being and depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders.

Highlights

  • Reviewed by: Mattie Tops, VU University Amsterdam, Netherlands Fieke Maria Antoinet Wagemans, Tilburg University, Netherlands Sayamwong E

  • Utilizing a randomized, placebo-controlled design in 60 patients with treatment-resistant depression, we found that peripheral blockade of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha with a biologic agent too large to cross the blood-brain-barrier produces antidepressant effects similar in magnitude to those seen with standard antidepressants in individuals with elevated baseline concentrations of peripheral inflammatory biomarkers [i.e., C-reactive protein (CRP) and TNF-alpha], while having no effect, or a detrimental effect compared to placebo, in patients with progressively lower baseline levels of these same biomarkers (Raison et al, 2013)

  • ANTIDEPRESSANT PROPERTIES OF THEMOSENSORY STIMULATION: EVIDENCE FROM WHOLE-BODY HYPERTHERMIA (WBH) Animal studies We have shown in rodent models that whole-body hyperthermia (WBH) activates serotonergic neurons in the midbrain [DRI and dorsal raphe nucleus, ventrolateral part (DRVL)] that are implicated in both thermoregulatory cooling and antidepressant and anti-anxiety behavioral effects (Hale et al, 2011), while avoiding activation of other subregions of the dorsal raphe nucleus, including the dorsal part of the dorsal raphe nucleus (DRD), which has been implicated in the facilitation of anxiety states (Lowry et al, 2005, 2008b; Lowry and Hale, 2010; Rozeske et al, 2011)

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Summary

Introduction

Reviewed by: Mattie Tops, VU University Amsterdam, Netherlands Fieke Maria Antoinet Wagemans, Tilburg University, Netherlands Sayamwong E. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects.

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