The leptin hypothesis of depression: a potential link between mood disorders and obesity?

Abstract

SummaryThe adipose-derived hormone leptin is well known for its function in the control of energy homeostasis. Recent studies suggest a novel role for this adipokine in the regulation of mood and emotion. Low levels of leptin have been found to be associated with depressive behaviors in rodents and humans. Pharmacological studies indicate that leptin has antidepressant-like efficacy. Both leptin insufficiency and leptin resistance may contribute to alterations of affective status. Identifying the key brain regions that mediate leptin's antidepressant activity and dissecting its intracellular signal transduction pathways may provide new insights into the pathogenesis of depression and facilitate the development of novel therapeutic strategies for the treatment of this illness.

Amylin-induced downregulation of hippocampal neurogenesis is attenuated by leptin in a STAT3/AMPK/ERK-dependent manner in mice

“…In Alzheimer's disease, the hippocampus is one of the first regions of the brain to suffer damage; memory problems and disorientation appear among initial symptoms [24,31]. It has been shown that leptin facilitates spatial learning and memory [14][15][16] and that it produces antidepressant-like effects [17][18][19][20][21][22]. It has also been proposed that high levels of leptin are associated with lower rates of dementia and Alzheimer's disease [31].…”

“…Recent findings demonstrate that leptin facilitates spatial learning and memory [14][15][16] and produces antidepressantlike effects [17][18][19][20][21][22]. Amylin has a beneficial effect on the CNS to alter physiological responses to feeding [23].…”

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

“…Recently significant interest has arisen in possible interactions between central mood substrates and circuitries involved in metabolism (Gomez-Pinilla, 2008;Krishnan and Nestler, 2008;Kuperman et al, 2010;McBriar, 2006;Shao et al, 2008). More specifically, several neuropeptides with a clear role in metabolism, such as leptin, ghrelin, orexin, neuropeptide Yand urocortin 3, produce clear anti-depressant-like responses (Eaton et al, 2007;Heilig, 2004;Kuperman et al, 2010;Lu, 2007;Lutter et al, 2008;Yamada et al, 2011), whereas e.g. melanin-concentrating hormone and cholecystokinin evoke a pro-depressant-like phenotype in several rodent models (Becker et al, 2008;Georgescu et al, 2005).…”

Involvement of psychosocial factors in the association of obesity with periodontitis

“…Several studies have found a social gradient in both work stress and metabolic syndrome (41)(42)(43), suggesting that the social gradient in metabolic syndrome and heart disease may be partly explainable by greater exposure to work stress Table 1 Means, standard deviations, Cronbach's Alpha and interscale correlations (n = 79) among less advantaged social groups. Metabolic syndrome and obesity have also been linked to several other psychological factors: body dissatisfaction, self-esteem, depression (44)(45)(46), stress (47)(48)(49), and positive and negative affect (50)(51). In line with previous reports, our study revealed that, in comparison with controls, overweight participants had significantly higher values of depression (6.75 ± 2.87 vs. 4.93 ± 3.32, P < 0.05) and anxiety (7.33 ± 2.68 vs. 6.03 ± 2.92, P < 0.05), and lower levels of optimism (15.13 ± 3.69 vs. 17.85 ± 3.95, P < 0.01) and satisfaction with life (21.49 ± 5.77 vs. 24.70 ± 6.80, P < 0.05).…”