Leptin, Somatic Depressive Symptoms and the Metabolic Syndrome: a Comment on Chirinos et al.

Abstract

People with depression are at increased risk of metabolic syndrome and vice versa [1]. Leptin, a hormone secreted by adipose tissue is a plausible link as levels are increased in people with obesity and depression [2, 3]. The article by Chirinos et al. [4] replicates previous findings and adds new evidence to the field: the association of circulating leptin levels with somatic depressive symptoms. In the study by Chirinos et al. [4], somatic but not cognitive depressive symptoms were associated with increased plasma leptin levels in 135 subjects with metabolic syndrome. These results, together with another recent study linking somatic depressive symptoms with C-reactive protein, interleukin-6 and tumour necrosis factor-α levels [5] suggest that adipokines and inflammatory markers may have a pathogenic role in the expression of somatic depressive symptoms. Interestingly, the association between leptin and somatic depressive symptoms was only found in men [4], which is in accordance with other studies reporting sex differences in the relationship between leptin and depressive symptoms [3], especially in socially isolated men [6]. We have also found a positive association between leptin and poorer neuropsychological performance in men with type 2 diabetes [7]. As animal models suggest that brains of male and female rats are differentially sensitive to the effects of leptin, with reduced effects in male rats [8], it is plausible that the association between leptin and neuropsychiatric symptoms in men may be explained by sex differences in leptin sensitivity at key brain areas (e.g., hypothalamus, hippocampus). Of all different somatic symptoms, Chirinos et al. found appetite disturbances, fatigue and sleep difficulties were associated with higher leptin levels [4]. Insomnia is a prevalent symptom in major depression and lack of sleep is also thought to be a risk factor for obesity and metabolic syndrome [9]. Anatomical factors related to obesity (reduced pharyngeal lumen size, decreased upper airway muscle force, reduced upper airway size) may cause obstructive sleep apnoea, which contributes to sleep difficulties. However, other patients with obstructive sleep apnoea show instability in ventilatory control that exacerbates otherwise minor anatomical deficits [10]. Hormonal factors secondary to obesity may also contribute to sleep disturbances. Increased serum leptin levels are associated with reduced respiratory drive and a reduced hypercapnic response in obese subjects [11]. As it is difficult to knowwhich is cause, and which effect in the association betweenmetabolic syndrome and obstructive sleep apnea [10], further prospective studies are needed to explore whether the development of leptin resistance may mediate this relationship. What other factors may be important in the relationship between leptin and sleep changes or appetite disturbances? Circadian alignment, quality sleep and sleep architecture are key elements of the energyand food-reward homeostasis [12]. Such chronobiological factors are also relevant in major depression (diurnal variance of mood, insomnia, seasonal pattern in recurrences) [13] and obesity (increased risk in shift workers, sleep deprivation, and exposure to bright light at night) [14].Moreover, genes related to the circadianmolecular machinery have been associated with major depression [15] and the metabolic syndrome [16]. As circadian misalignment affects sleep architecture, glucose insulin metabolism and leptin concentrations [12], further studies are needed to address whether the relationship between leptin and sleep problems in depression is influenced by chronobiological factors. J. Labad (*) Hospital Universitari Institut Pere Mata, IISPV, Universitat Rovira i Virgili. CIBERSAM, Ctra. de l’Institut Pere Mata, s/n, 43206 Reus, Spain e-mail: labadj@peremata.com