Abuse, Attachment, and Resilience: Genes and the Environment (with Dr. Nemeroff, part 2 of 2)

Charles Nemeroff, MD, PhD, discusses the role of social influences on biology, using the example of early life trauma. He explains brain changes, inflammation, and genetic risk factors that modulate the development of PTSD or depression in patients with a history of trauma.
Keeping in line with epigenetic theory, Dr. Nemeroff discusses what happens to genes during psychotherapy, exploring the interaction between attachment to the therapist and how this contributes to the efficacy.
Finally, he answers our rapid-fire questions and describes the challenges without parity in mental health care. He leaves us with excitement and hope for what he feels is the “golden age of psychiatry.”
TRANSCRIPT
David Carreon: I think that on the positive end, I think there's more research to do, but I think thinking about this relationship between the mind and the body, and the person's experience ... It makes me think of things like a difficult childhood, child abuse, or something like that could very well increase a person's stress level and inflammatory markers.
Dr. Nemeroff: Well, you're prescient, because that's exactly what the data show. There's a wonderful meta-analysis by Andrea Danese at the Institute of Psychiatry in London. We've confirmed the findings in our own studies. Early life trauma is associated with a very persistent increase in inflammatory markers, and it's probably one of the reasons why those patients have a poorer response to psychotherapy and pharmacotherapy.
Jessi Gold: And what counts as early life, and is it one trauma, multiple traumas, or is it different?
Dr. Nemeroff: So another great question. The data is still being generated, but overall pre-pubertal abuse and neglect. The more severe, the worse the outcome, both in terms of inflammation, but also a host of other factors. Neuroanatomical changes ... The human brain doesn't mature until age 24, and we know that developing protoplasm is susceptible to insult. Susceptible to lead toxicity, susceptible to fetal alcohol, and in my way of thinking, it's susceptible to behavioral teratology, namely child abuse and neglect. So it's not surprising that we've seen these robust effects that we have.
David Carreon: Yeah, and I think there's been an interesting body of literature developing around the social influences on biology. Rats that are isolated versus rats that are in paired housing versus rats that are in enriched environments have entirely different profiles of how they do and how they behave, and what that means for them. And I guess thinking about that both in childhood, but throughout the life, that environment plays a huge role ... And social environment plays a huge role in-
Dr. Nemeroff: Well, remember that for major depression ... Not talking about bipolar disorder, but for major depression, about 35 to 40% of the risk for the disease is genetic. That means 60 to 65% is environmental, and I think a lot of this has to do with attachment. I think early life trauma disrupts attachment, and I think subsequent life stressors disrupt attachment, and if you follow these kids who've had terrible early lives, it's a very rocky adolescence and adulthood indeed.
David Carreon: Is it possible that somebody who has had a difficult childhood would be able to overcome that and fully remit or fully...
Dr. Nemeroff: Yeah, so most of our studies in this area have focused on trying to uncover genetic risk factors, that interact in a gene environment way to increase or modulate the risk for depression or PTSD in adulthood. What we've discovered is that there are some critical genes, of which certain of the SNPs, the variants, unfortunately markedly increase your risk for depression if you've been exposed to early trauma, and then their counterparts which are resilience genes that prevent it.
So I believe many of our patients are probably patients who've just had pretty bad luck. They've pulled a bad hand. They have three, four, five or six of the vulnerability genes coupled with early life trauma that result in an increased risk for depression. What's really interesting is in our studies, in the absence of early life trauma, these genetic variants have no impact on whether you get depressed or not. It's only in the face of early life trauma. It's sort of like ... Imagine the guy who has the risk gene for lung cancer but never smokes, right? No effect, right? But smokes three packs a day and 80% likelihood. That's what Caspi saw with the serotonin transporter gene. It's we've seen with the CRH and the FKBP5 gene. I don't want to bore you with the nomenclature, but there are gonna be a category of genes.
Now there is some data that both epigenetics is important, so the notion that life events change gene expression, not by changing the structure of the gene but by changing the expression of genes. That could be good or bad. It may be, if I was a betting person and I was Jessi's age, what I would do ...