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Monday, August 25, 2014

Obesity, depression, phobia and genes

The prevalence of clinical depression is about one third higher among obese versus non-obese subjects and there is conflicting evidence as to whether it is depression that brings on obesity or the reverse, where obesity brings on depression. To study this conundrum, a recent research project examined data from a longitudinal study of 18, 558 British individuals born in 1958[1]. This cohort was followed up at 7, 11, 16, 23, 33, 42, 45 and 50 years. Subjects were rated as underweight, normal weight over weight or obese. Those that were underweight had 1.3 to 2.3 times the risk of being depressed compared to those of normal weight. There was no evidence of a tendency toward depression among the overweight but among the obese, the risks of depression were between 1.5 and 2.3 times that of normal weight subjects. The data were then examined to see how either one of the conditions (obesity or depression), in prior years influenced the likelihood of the other condition subsequently developing. Being underweight predicted subsequent depression in both males and females (25% higher that those of normal weight) and depression predicted subsequent underweight in males only  (84% higher risk). Obesity predicted subsequent depression in females only (34% higher risk). However, depression did not predict subsequent obesity. In all these calculations, confounding factors such as social class, physical illness and ethnicity were controlled for.  The authors reflect on the fact that the treatment of obesity should also include an examination of possible depression but they ignore the elephant in the room, which is the stigmatization of the obese. By and large, the overweight and obese are seen by society, including health professionals, as having themselves to blame. They are seen as lazy, dishonest, untidy, lethargic, unreliable and so on. Sympathy with the overweight and obese is a rare occurrence.

A second paper[2] looking at a related topic, namely phobic anxiety, obesity and genes is also worth considering. Phobic anxieties relate to a wide range of fears that some people experience and the level of anxiety is measured on the Crown Crisp Index, which includes, for example, measures of claustrophobia fear of heights and crowds or hypochondriac traits. The subjects were participants in the Harvard based Nurses Health Study (5,911 females) or the Health Professional follow-up Study (3,697 males). They used genetic data on 34 genes linked to obesity. One was the FTO gene, which is the most widely studied such gene and another was the gene for a brain receptor involved in appetite regulation (MC4R). The remaining 32 genetic variants had been previously identified as increasing the risk of obesity in another study and were termed obesity risk genes. One of these 32 genes was also the FTO gene and these 32 genes had an additive effect on the risk of obesity. Average phobic anxiety scores were more 43% higher in women, which agrees with the general literature. The relationship between genetic factors and BMI was strong for the FTO gene, the MC4R gene and the 32 obesity risk genes. Higher BMI values increased the risk of phobic anxiety only among those carrying the common FTO genetic variant. After adjusting to an average BMI value, the FTO gene variant still had a direct association with phobic anxiety. Taken together, these data show that there is a common genetic link between obesity and phobic anxiety. The authors ask that their findings should be treated with caution and their hypothesis should be studied in larger samples. The finding that the collection of genes that had a linear rise in the risk of obesity did not link with anxiety suggests that obesity per se is not a cause of phobic anxiety and that the two conditions, obesity and phobic anxiety simply share a common genetic pathway

All in all, these two papers highlight the need for the study of the psychological conditions associated with obesity and they further highlight the need to study the reverse: how do psychological conditions contribute to energy imbalance

[1] Geoffrey, M and Power C (2014) Psychological Medicine, 44, 2461-2652
[2] Walter S et al (2014) Psychological Medicine, e publication  ahead of print: PMID: 25065638

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