Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat

Harvard University, Cambridge, Massachusetts, United States
Clinical Endocrinology (Impact Factor: 3.46). 07/2011; 76(4):520-5. DOI: 10.1111/j.1365-2265.2011.04182.x
Source: PubMed


Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum.
64 women: 15 with AN, 12 normal-weight with HA, 17 overweight or obese (OB) and 20 normal-weight in good health (HC).
Fasting serum leptin and plasma ghrelin levels were measured. Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Perceived Stress Scale were administered.
Leptin levels were inversely associated with HAM-D, HAM-A and Perceived Stress scores. The negative relationships between leptin and severity of symptoms of both depression and anxiety remained significant after controlling for body fat or weight. There was no relationship between ghrelin and symptoms of depression or anxiety. Although ghrelin levels were positively associated with the degree of perceived stress, this relationship was not significant after controlling for body fat or weight.
Leptin may mediate depressive symptoms across the weight spectrum. Further investigation of the role of leptin in modulating mood will be important.

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    • "Therefore, chronodisruption in appetite hormones may provoke a disregulation in the aminergic pathway and vice versa. A study that investigated the relationship between leptin levels and ghrelin as well as symptoms of depression, anxiety and stress in women demonstrated a significantly negative relationship between leptin and the severity of depressive symptoms and anxiety (Lawson et al., 2012). Females present a greater expression of clock genes in adipose tissue, and consequently, it has been hypothesized that this sexual dimorphism may account for the different CT of males and female (Gómez-Abellán et al., 2012). "
    Personality and Individual Differences 04/2014; 60:S18. DOI:10.1016/j.paid.2013.07.384 · 1.86 Impact Factor
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    • "Although we hypothesized that emotional symptoms might be associated with leptin, we did not observe a significant association after adjustment for confounding variables or in the fasting serum leptin sample, indicating that emotional symptoms are associated with leptin to a lower degree in children. However, there is inconsistent evidence for depression and its association with leptin levels among adult populations (Antonijevic et al. 1998; Kraus et al. 2001; Rubin et al. 2002; Esel et al. 2005; Jow et al. 2006; Yang et al. 2007; Pasco et al. 2008; Lawson et al. 2011). Our results of a differential effect of emotional symptoms and peer problems may indicate that both categories capture different forms of social or psychological stress-related problems. "
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    ABSTRACT: Background: Leptin is thought to act as an important mediator in stress reactions. To date, no study has examined the association between psychological stress and leptin levels in children. This study aimed to assess the association between emotional symptoms and peer problems and serum leptin levels in children aged 10 years of the two population-based GINI-plus and LISA-plus birth cohorts. Method: Cross-sectional data from 2827 children aged 10 years were assessed with regard to leptin concentrations in serum and behavioral problems using the parent-reported Strengths and Difficulties Questionnaire (SDQ). Linear regression modeling was applied to determine the likelihood of elevated leptin levels in children with emotional symptoms and peer problems, controlling for socio-economic status (SES), body mass index (BMI), fasting serum leptin levels, pubertal development and sex hormones. Results: We found that increases in emotional symptoms (exp β adj = 1.03, s.e. = 0.02, p < 0.04) and peer problems (exp β adj = 1.05, s.e. = 0.01, p = 0.0001) were significantly associated with higher serum leptin levels controlled for BMI and sociodemographic factors. Similar results were found when the fasting serum leptin sample was examined (exp β adj = 1.08, s.e. = 0.04, p = 0.0294). Gender-stratified analyses showed a significant relationship between serum leptin and peer problems in girls (exp β adj = 1.05, s.e. = 0.02, p = 0.03), and a borderline significant association in boys (exp β adj = 1.04, s.e. = 0.02, p = 0.05). Conclusions: Children with peer problems have higher stress and eat more, acquire a higher body fat mass and thus, through increased leptin resistance, exhibit higher leptin levels.
    Psychological Medicine 04/2013; 44(02):1-11. DOI:10.1017/S003329171300069X · 5.94 Impact Factor
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    • "Leptin deficient mice display increased depressive and anxiety–related behaviors and overexpression of leptin has been shown to exert antidepressant and anxiolytic effects [20], [46], [47]. In clinical studies, leptin levels have been associated with both increased and reduced depressive symptoms [48], [49], [50]. As both patients with HD and mouse models of the disease display altered leptin levels, it would be possible that leptin could play a role in the development of psychiatric features in HD. "
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    ABSTRACT: Metabolic and psychiatric disturbances occur early on in the clinical manifestation of Huntington's disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. Hypothalamus has emerged as an important site of pathology and alterations in this area and its neuroendocrine circuits may play a role in causing early non-motor symptoms and signs in HD. Leptin is a hormone that controls energy homeostasis by signaling through leptin receptors in the hypothalamus. Disturbed leptin action is implicated in both obesity and depression and altered circulating levels of leptin have been reported in both clinical HD and rodent models of the disease. Pathological leptin signaling may therefore be involved in causing the metabolic and psychiatric disturbances of HD. Here we tested the hypothesis that expression of mutant HTT in leptin receptor carrying neurons plays a role in the development of the non-motor phenotype in the BACHD mouse model. Our results show that inactivation of mutant HTT in leptin receptor-expressing neurons in the BACHD mouse using cross-breeding based on a cre-loxP system did not have an effect on the metabolic phenotype or anxiety-like behavior. The data suggest that mutant HTT disrupts critical hypothalamic pathways by other mechanisms than interfering with intracellular leptin signaling.
    PLoS ONE 12/2012; 7(12):e51168. DOI:10.1371/journal.pone.0051168 · 3.23 Impact Factor
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