More Clues to Systemic Inflammation in Mood Disorders

Continuing from the discussion of bipolar disorder and adipokines, There's a lot of intriguing information in various studies about the systemic inflammation found in bipolar disorder.  One of the more interesting papers was done by Kapczinski et al and published in 2011 in Psychiatric Research:  Peripheral biomarkers and illness activity in bipolar disorder.

(Classical today  - Bizet, L'Arlesienne, starting in the middle.  At three minutes is one of my favorite classical lullabies, the Adagietto from the Suite L'Arlesienne.)

The researchers measured a bunch of things in the blood known to be associated with systemic inflammation both in serious disease (blood infections, for example) and in mental illness, including the inflammatory cytokines IL-10, IL-6, TNFalpha, the brain "fertilizer" known to be low in depression and manic episodes, BDNF, and other measures of oxidative stress (which means, imperfectly, that the engines in the cells aren't running efficiently and pumping out some toxic byproducts, causing damage to proteins and fats) and lipid peroxidation such as PCC, TRAP, and TBARS.  There's an awful lot of statistics in the paper, which is always suspicious ;-) but also seems to be a fair way of dealing with a complex set of observational data.

Several groups of people were compared.  A set of healthy controls without any major medical illness or any personal or close family psychiatric history,  known bipolar patients who were currently experiencing normal mood (or "euthymic" as they say in the biz), bipolar patients who were depressed, bipolar patients who were hospitalized for mania, and seriously medically ill patients who were hospitalized in the ICU for infection.  This last group was a "negative control" to see if there were any similarities or differences in the cytokine and measures of stress in the body in the very medically ill compared to the psychiatric patients.

The researchers found that the healthy controls and euthymic bipolar patients were fairly similar.  They also found that the manic and depressed patients (more the manic, who were hospitalized, while the depressed were selected from an outpatient population) had surprising measures of lipid peroxidation, protein damage, and oxidative stress.  These measures in some cases were similar to the medically ill patients who were basically on death's door with sepsis.

The sobering conclusion one could think about is that mood episodes are very stressful and potentially very damaging to the body.  None of these measures were of the cerebrospinal fluid.  Everything was done with a blood draw from the body.  The other conclusion is that folks with known bipolar disorder who were not acutely ill had bounced back to a healthy state, cellularly speaking.  The researchers, most of whom had funding from one pharmaceutical company or another, made the case that aggressive prophylactic treatment of mood disorders was warranted to prevent serious mood episodes.

This argument, along with other evidence from certain longitudinal studies, is used in psychiatry today to promote aggressive pharmacologic treatment.  It is absolutely true that the more mood episodes one has, the more likely one is to have even more episodes in the future, and the harder the future episodes are to get under control.   If these illnesses are pounding your brain and body, decreasing number of manic or depressive episodes via any means necessary would seem to be the logical thing to do.

The problem for a psychiatrist in the field is that we know the studies are stacked in favor of pharmaceuticals.  These issues are discussed at length and in detail in many better blogs than mine (I'll link to the Carlat Psychiatry Blog* as an example).  I'm a psychiatrist, I've seen meds work, I've seen them work and cause major problems, and I've seen them fail miserably.  I've seen EMDR, DBT, neurofeedback, and various forms of behavioral and psychodynamic therapy also work or not (sometimes causing major problems) depending upon the circumstances.  But part of the reason I look at alternatives is because I think there is too much focus on both meds (and talk therapy, in the classic psychiatry circles and in psychology in general) when there are so many other modalities of treatment and lifestyle modification that could also be helpful, and in many cases less likely to cause harm.  What I pull from studies like the one I linked above is that bipolar disorder, like diabetes, deserves a full-bore approach, with support focusing on good nutrition, appropriate sleep and exercise, addressing problems with coping strategies or relationships, and medications when indicated.

Common sense.  Wedded with an understanding of the patient born of time and attention and experience dealing with people.  

*That particular blog article discusses what I found to be a surprising rant by Stephan Stahl, a celebrated and likable psychiatrist who has written several textbooks on pharmacology and runs an education company.  He's a biological psychiatrist and a whiz with meds, but when I read his books I feel a bit empty, because there is so much we do not know about what these medications do in vivo compared to the theory, particulary in the combinations used in common practice today.