The 'Single Biggest Contributor' to Medical and Mental Illness

This transcript has been edited for clarity.

Stephen M. Strakowski, MD: Hello. I'm Dr Stephen M. Strakowski, acting senior associate dean for research at the Dell Medical School at the University of Texas at Austin. I'm speaking today with two of my expert colleagues here. Dr Elizabeth Lippard is an assistant professor in our department and has been here the longest of anybody else other than me. Dr Charles Nemeroff joined us about a year ago and is now acting as chair in the department of psychiatry, in addition to creating and directing the Institute for Early Life Adversity Research.

We're speaking with Drs Lippard and Nemeroff about a seminal paper they just published in the American Journal of Psychiatry, reviewing the impact of early life adversity on people, their lives, their medical history, and potentially what goes on in the brain. I want to talk with them today about how all of us who practice mental health care might apply their important work.

To begin, can you tell us about the field of early life adversity and how common such experiences are in patients?

Charles B. Nemeroff, MD, PhD: The entire field was really launched by the phenomenal Adverse Childhood Experiences (ACE) Study, which was funded by the Centers for Disease Control and Prevention (CDC). Investigators went to Kaiser Permanente in San Diego and sampled 17,000-plus individuals.

The results were just astounding. In this nonclinical general population, the rates of child abuse in the form of physical abuse, sexual abuse, emotional abuse, and neglect were remarkably high, ranging—depending on the category—from about 8% to 25%. These results have since been confirmed in several subsequent studies from the CDC and others. This is really a public health tragedy.

Strakowski: It sounds like an epidemic. If we imagined a new virus suddenly affecting 1 in 4 kids, I assume that people would be quite upset and doing something about it.

Nemeroff: This is the single biggest contributor to the risk for psychiatric and medical disorders, more than any single gene or factor. It increases the risk for heart disease, stroke, depression, drug abuse, suicide. It's awful.

Strakowski: How should people be thinking about the potential impact of these risks?

Elizabeth Lippard, PhD: Piggybacking on what Charlie was saying, if you look at the prevalence of childhood maltreatment, early life stress, and mood disorders, you see rates as high as 50%-60%. If you look at individuals with mood disorders and comorbid addiction, rates are even higher.

We consistently see across studies that it's associated not only with increased risk for onset, but also increased risk for disease recurrence. In terms of mood disorders, this means more mood symptoms occurring over time with greater severity. You also see a relationship in terms of more complicated clinical cases: more comorbidities, with addiction and medical morbidities as well.

Considering the clinical impact that it's having on disease outcomes, and how prevalent child maltreatment is, this is a large percentage of disease burden that can be directly contributed to early life stress. It points to a very powerful target that we need to be thinking about when treating disease.

Strakowski: I think when a lot of us consider these kinds of abusive histories, we tend to then jump to post-traumatic stress disorder (PTSD) as the only consequence that we need to contemplate. But you're saying that it's much broader than that.

Lippard: Yes, definitely. Whenever you think about childhood maltreatment, it really crosses diagnostic boundaries. It increases the risk for mood disorders, addiction, PTSD, schizophrenia, etc., and you see it across the board.

The Physical Tolls of Early Trauma

Nemeroff: If you look at victims of child abuse and neglect when they are adults with psychiatric disorders, they are much more treatment resistant than patients with comparable disease severity without this history. We believe that the reason for that is that early life trauma results in brain and body changes that persist for the lifetime of the individual. These folks have a different biology, a different brain, and their treatment response for bipolar disorder, for depression, for PTSD is just terribly worse than it is for people without this history.

Strakowski: You perfectly anticipated my next question. Do we have some idea of what early life trauma is doing to the person's brain or body that is setting them up for these consequences?

Lippard: We do. There's a wealth of research out there pointing toward long-lasting neurobiological and immune mechanisms, as well as the hypothalamic pituitary adrenal stress response system, and changes within these systems that may be contributing to these outcomes.

In terms of the brain, we see long-lasting changes in structure and function within systems that regulate stress response and emotional, higher-order cognitive processes. It really is giving us an insight into the brain systems that may be so critical for developing psychopathology over time following childhood maltreatment.

One of the things that's really striking to me when you look at the literature is the more recent emergence of longitudinal studies, which suggest that changes in the brain really can predict future mood symptoms, recurrence, and severity. Traditionally, we started with a wealth of cross-sectional studies in this area, but now these longitudinal studies coming out have given us a lot of power to hone in on certain systems of the brain that can hopefully be targeted for intervention.

Ask Patients About Their Childhoods, Regardless of Your Specialty

Strakowski: Clinicians and providers across many different specialties will be watching this. This applies to patients with psychiatric conditions but, as you implied, medical conditions as well. How do you recommend they ask their patients about this?

Nemeroff: First, for the clinicians out there, it's extremely important that you get this information from the patient. You need to know it.

There are several screening tools available to help you obtain this information. There's the ACE questionnaire, although I'm not particularly fond of it. I think the Childhood Trauma Questionnaire is somewhat better. There are others as well. These are self-rating scales, so they won't take any of your time. We have every patient fill out the scales, which gives you a good indication of their history, as patients will often put things down on paper that they don't want to tell you.

Second, it often takes several visits with a patient before they're comfortable enough to talk about their trauma. I've seen many patients with treatment-resistant depression who finally revealed to me that they had suffered a childhood rape or some other awful experience. If you're seeing a treatment-resistant patient, you should be thinking about child abuse and neglect.

Strakowski: In anticipating my talk with you both today, I gave some thought to my own clinical practice. On a given day in my clinic, I bet 80% of the young people I treat have these histories. It's hard to overexaggerate the risk.

An Epidemic Without a Solution

Strakowski: From a treatment perspective, do you consider maybe doing something differently if you are aware that a patient has this history?

Nemeroff: We know that in every study that we looked at, when you parse out the patients with early life trauma and compare them to those who don't have that history, they have a poorer outcome. But part of the problem is that there are no treatment trials that have specifically asked this question. In terms of designing a treatment, my gut feeling, which is not science, is that they would do better with a combination of pharmacotherapy and psychotherapy.

One of my concerns is that, as pharmaceutical companies come to realize that these patients actually have poor treatment outcomes, they're starting to eliminate them from clinical trials.

Strakowski: Which is the exact opposite of what we wish would happen.

Nemeroff: It's sort of like what's happened with pregnancy; we don't know how to treat pregnant women because they're never allowed in trials.

Strakowski: To me, it sounds like we have an epidemic for which we're not aggressively trying to find a solution. Does it feel like the psychiatric or psychological professional associations and organizations are making this issue sufficiently visible to engender some response?

Nemeroff: I think that a number of the organizations you're referring to have done their best, but it's not enough. First, from a medical education point of view, there is very little training about child abuse and neglect in the curriculum.

Strakowski: I probably received none, roughly 200 years ago when I was in training, and I'm guessing the same is true for you.

Nemeroff: Absolutely. There's very little attention paid to this. Of all of the physicians, I think pediatricians have been the most sensitive to this. But as Beth alluded to, this a population with an increased risk for diabetes, certain forms of cancer, heart disease, and stroke, and specialists in those areas don't ask about child abuse and neglect.

Strakowski: There's a lot more detail to this very important topic in the paper, authored by Drs Lippard and Nemeroff, which is titled "The Devastating Clinical Consequences of Child Abuse and Neglect: Increased Disease Vulnerability and Poor Treatment Response in Mood Disorders." I hope you all will take a look at that, and I hope you found our conversation interesting. Thank you all for listening today.

Stephen Strakowski, MD, is the founding chair and professor of psychiatry at Dell Medical School, University of Texas. His research focuses on the brain changes that occur at the onset of bipolar disorder.

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