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Friday, April 20, 2012

Obesity, Systemic Inflammation, and Bipolar Disorder


Mental illness is not invented, and psychiatry is not all in your head.  Today an exploration of the link between bipolar disorder and obesity.  And there is a link, despite the tremendous confounding fact that most of the medicines used to treat bipolar disorder definitely cause obesity, researchers separate out the medication component (and also look at reports from history, prior to medications even being available) to find a strong correlation.  But why, and how?

Cool song: Howler, Back of Your Neck. (right click to open in new tab)

Well, I don't have any definitive answers for you today as to the ultimate cause of bipolar disorder and why it is linked with obesity.  What we do have is a little recent observational study, Increased Levels of Adipokines in Bipolar Disorder that can serve as a handy review of some of our obesity hormones.  

Everyone, I'm assuming, has heard of insulin, and probably leptin.  Leptin is an adipokine, a chemical mediator produced by the fat tissue that can help tell the body how much fat is on board.  Most of you will know that leptin tends to be increased in obese folks, suggesting that obesity may be a function of leptin resistance.  There are other adipokines besides leptin, however, including resistin and and adiponectin.  Adiponectin is of particular interest, because it is known to be anti-inflammatory, the body makes quite a bit of it relative to other hormones, and its levels inversely correlate with obesity in adults.  Leptin is thought to be pro-inflammatory, and may be responsible for the activation of an inflammatory cytokine, TNF-alpha.  Adiponectin will help to decrease the production of TNF-alpha.  So, in general, an obese person will have lower than normal adiponectin and higher than normal leptin, with associated increases in inflammation.

In the study, 30 bipolar (type I) patients were compared with 30 matched (age, BMI, education level, and gender) controls.  All the bipolar patients were on medication (a huge weakness of the study).  Compared to the matched controls, the bipolar patients had higher levels of adiponectin, leptin, and one of the receptors for TNF-alpha.  The kind of medication (as the patients were on several different classes) and medical co-morbities did not correlate with the hormone levels.  Since, again, adiponectin is generally lower in obese individuals, it is interesting that the bipolar patients had higher levels than the controls of the same age, gender, and BMI.  

One previous study of obese bipolar patients showed the same increase in adiponectin.  A study of non-obese depressed bipolar patients had adiponectin levels lower than the controls.  Leptin has been more vigorously studied, and the levels are elevated in some and not in others. The only other study of previously manic but now normal mood patients had the same leptin levels (elevated).  

It's interesting, though we don't quite know what it means.  We get a hint of a large puzzle of a systemic illness, affecting mood, sleep, appetite, thought, immunity, and the adipose tissue.  The connecting process of inflammation is not controversial.  What causes the inflammation� that we don't yet know, and it is likely a confusing combination of factors.  There are a number of papers exploring, for example, peripheral biomarkers and different moods in bipolar disorder, helping us to figure out other pieces of the puzzle.  No one has all the answers. 





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