Sunday, February 27, 2011

Social Isolation and Depression Are More Harmful In Men than in Women

This study from Psychoneuroendocrinology suggests that for men (but not for women) social isolation and the corresponding depression causes a chemical change in the body that may lead to obesity and heart disease.

Here is the abstract, then a little explanation below. Unfortunately, it's not open access.

Social isolation and depressed mood are associated with elevated serum leptin levels in men but not in women

S. Häfnera, A. Ziererb, R.T. Emenyb, B. Thorandb, C. Herderc, W. Koenigd, R. Rupprechta, K.H. Ladwigbe, for the KORA Study Investigators

Received 24 February 2010; received in revised form 10 June 2010; accepted 8 July 2010.



Leptin, involved in energy homeostasis and a predictor of cardiovascular disease, has recently been recognized as mediator in stress reactions. We aimed to explore the association between leptin levels and two stress-related conditions, social isolation and depressed mood, both associated with increased cardiovascular mortality.


We analysed leptin levels in 1229 subjects (643 men, 586 women), derived from the population-based MONIKA/KORA study. Standardized questionnaires were used to assess depressive mood and social isolation. In a multiple linear regression adjusted for body weight, age and survey, the association between leptin, social isolation and depressed mood and its interaction was explored in men and women separately. Leptin was then dichotomized and four analyses, adjusted for age, BMI, lifestyle factors, psychosomatic complaints and metabolic variables were performed to compare the risk of elevated leptin levels in the risk groups.


Increased leptin levels were associated with social isolation (p=0.04) and the interaction between social isolation and depressed mood (p=0.02) in men but not in women. In socially isolated and depressed men, leptin levels (mean: 6.07ng/ml) were significantly increased compared to neither depressed nor isolated men (mean: 4.51ng/ml, p=0.04). In the multivariate adjusted logistic regression model, the combination of depressed state and social isolation was associated with a 4-fold increased risk (p0.001) for elevated leptin levels.


The finding of elevated leptin levels in socially isolated and depressed men raises the possibility that increased cardiovascular mortality in socially isolated men is partially mediated by hyperleptinemia.

Full citation:
Häfner S, Ziererb A, Emeny RT, Thorand B, Herder C, Koenig W, Rupprecht R, Ladwig KH. (2011, February). Social isolation and depressed mood are associated with elevated serum leptin levels in men but not in women. Psychoneuroendocrinology, Volume 36, Issue 2, Pages 200-209. doi: 10.1016/j.psyneuen.2010.07.009

When leptin was discovered a few years back (well, maybe 20 years ago now), it was thought to be the breakthrough in helping the body control its bodyfat levels. In mice, as in humans, obesity is correlated with higher blood plasma levels of leptin.

When mice are given injections of leptin, their bodyfat decreases. Not so in humans. But the impact of leptin in mice is very impressive.
Genetically modified ob/ob [these mice are 3x as fat as normal mice on the same diet] mice show many of the abnormalities seen in starved animals, including decreased body temperature, hyperphagia, decreased energy expenditure (including activity), decreased immune function, and infertility (3). Leptin replacement corrects all of these abnormalities, implying that ob mice exist in a state of ‘perceived starvation’ and that the resulting biological response in the presence of food leads to obesity (13,17,23,24). The idea that decreased plasma leptin levels signal nutrient deprivation is supported by the observation that exogenous leptin attenuates the neuroendocrine responses to food restriction (25). Fasted wild-type mice receiving leptin continue to ovulate, whereas fasted controls given saline experience an ovulatory delay of several days. Leptin treatment blunts the changes in circulating thyroid hormone and corticosterone levels that are normally associated with food deprivation (25). Starvation is also associated with decreased immune function and leptin corrects these abnormalities (24). Leptin stimulates proliferation of CD4(+) T cells and increases production of cytokines by T-helper-1 cells (24). These results indicate that leptin may also be a key link between nutritional state and the immune system. (Friedman & Halaas, 1998)
Mice given leptin lose fat in a dose-dependent manner - and they suffer none of the health risks of starved mice. It seemed like a miracle drug. Except that in humans it does not work the same way - the only way to dose it effectively in humans is subcutaneously or in cerebral spinal fluid, neither of which are cost effective or practical.

So then why do obese rats/humans have higher leptin levels? For the same reason these subjects have higher insulin levels - resistance. Chronic high levels of leptin make the body insensitive to yet higher levels. Additionally, leptin is synthesized and expressed in adipose (fat) tissue, so the more fat one has, the more leptin is produced.

In mice, leptin can inhibit the hypothalamic-pituitary-adrenal axis (HPAA) reducing plasma corticosterone levels (stress hormones). However, in mice that have become leptin-resistant, it has no impact on plasma cortisol levels (Heiman, et al, 1997).

The same would appear to be true in humans - leptin levels in those who are socially isolated and depressed remain elevated despite the elevation of corticosteroids associated with stress. More importantly, chronically high leptin levels are associated with cellular stress in humans (Bouloumie, Marumo, LaFontan & Busse, 1999).

So the article at the top is slightly misleading in my opinion. High levels of leptin are simply a marker for other stress-related processes occurring in those who are socially isolated and depressed. It's unclear why men are impacted and not women. But this is useful information.

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