Eric Kandel on biological psychiatry

The new (?) science of mind:

In a recent study of people with depression, Professor Mayberg gave each person one of two types of treatment: cognitive behavioral therapy, a form of psychotherapy that trains people to view their feelings in more positive terms, or an antidepressant medication. She found that people who started with below-average baseline activity in the right anterior insula responded well to cognitive behavioral therapy, but not to the antidepressant. People with above-average activity responded to the antidepressant, but not to cognitive behavioral therapy. Thus, Professor Mayberg found that she could predict a depressed person’s response to specific treatments from the baseline activity in the right anterior insula.

These results show us four very important things about the biology of mental disorders. First, the neural circuits disturbed by psychiatric disorders are likely to be very complex.

Second, we can identify specific, measurable markers of a mental disorder, and those biomarkers can predict the outcome of two different treatments: psychotherapy and medication.

Third, psychotherapy is a biological treatment, a brain therapy. It produces lasting, detectable physical changes in our brain, much as learning does…

Matthew State, at the University of California, San Francisco, has discovered a remarkable copy number variation involving chromosome 7. An extra copy of a particular segment of this chromosome greatly increases the risk of autism, which is characterized by social isolation. Yet the loss of that same segment results in Williams syndrome, a disorder characterized by intense sociability.

This single segment of chromosome 7 contains about 25 of the 21,000 or so genes in our genome, yet an extra copy or a missing copy has profound, and radically different, effects on social behavior.

The second finding is de novo point mutations, which arise spontaneously in the sperm of adult men. Sperm divide every 15 days. This continuous division and copying of DNA leads to errors, and the rate of error increases significantly with age: a 20-year-old will have an average of 25 de novo point mutations in his sperm, whereas a 40-year-old will have 65. These mutations are one reason older fathers are more likely to have children with autism and schizophrenia.

The State paper is here. Of course, we should all remember the nature vs nurture debates: the expression of these genes are often influenced by the (social) environment.  I would argue that this intersection will be the most fruitful line of medical research in the coming decades.

How social status determines your health

You wouldn’t think how people perceive you could directly affect your health, would you?  Luckily, science is here to save the day and to tell you, you’re wrong.  A pair of papers published in PNAS in the last month have investigated the interaction between social status and health, and the findings compliment each other rather nicely.

The authors of the first paper tracked baboons over thirty years and made a compelling figure (show at right) showing that low-ranking males are sick more often, and for longer, than high-ranking males.  It has been theorized that the biological effects of high social status – testosterone, high glucocorticoids, high reproductive effort – would reduce health.  After all, if these high-ranking male baboons have to spend all their time and energy making sweet monkey love, there wouldn’t be much energy left over for healing, would there?  However, they found no evidence for this.  In fact, alpha males seemed to heal faster than anyone else.

The authors of the other paper examined the different genes that are regulated in low- and high-status female rhesus monkeys.  The previous paper tracked male animals in the wild, and this one kept female animals in the laboratory.  The authors took blood samples from the monkeys to profile gene expression – though only after dominance order had been established.  It would have been great had they done so before hand to see if there were genes predictive of social status, or if expression changed in any appreciable way.  But no matter.  By using a PCA analysis – basically, finding the combinations of genes that most explained the variance in the behavior – they found that the first principle component was predictive of social status.  This tells us that gene expression is intertwined with your social status.

Almost 1000 genes were found to be associated with rank, 535 of which were more enriched in high-ranking individuals and 452 of which were more enriched in low-ranking individuals.  So a lot is going on in there and getting changed!  Consistent with the previous paper, there was the largest cluster of enriched genes were immune-related.  This included interleukin signaling, T-cell activation, and chemokine/cytokine inflammation.  Perhaps, then, the reason high-ranking males heal faster is because the right immune-related genes were enriched.  But that leaves the question, why should that be so?

The paper included an excel spreadsheet of the enriched genes which can be a bit fun to scroll through; following on something I touched on in the previous post, I expected to find dopamine receptor genes enriched in one of the conditions but I didn’t.  Something to keep in mind.

I guess the moral of story here is: socializing is dangerous.  Or maybe not socializing is dangerous.  Either way, watch out!

References

Archie, E., Altmann, J., & Alberts, S. (2012). Social status predicts wound healing in wild baboons Proceedings of the National Academy of Sciences, 109 (23), 9017-9022 DOI: 10.1073/pnas.1206391109

Tung J, Barreiro LB, Johnson ZP, Hansen KD, Michopoulos V, Toufexis D, Michelini K, Wilson ME, & Gilad Y (2012). Social environment is associated with gene regulatory variation in the rhesus macaque immune system. Proceedings of the National Academy of Sciences of the United States of America, 109 (17), 6490-5 PMID: 22493251