Dr. Adam Brenner: A preventive guide on mental illness

It seems that a tragedy driven by mental illness takes over the headlines every few weeks.

Sometimes it’s a celebrity who commits suicide or overdoses on drugs. Maybe it’s a psychotic person who goes on a violent rampage. Or it could be a bullied teen who lapses into depression and despair and ends his or her life.

In each case, we’re all saddened by the tragedy and the terrible loss. Often, we undertake an important and necessary discussion about how we might improve our response to such crises and make our mental health safety net more secure.

But rarely is there a discussion of whether mental illness is preventable. We seem to believe it’s not. We know that smoking can lead to cancers and that poor nutrition and obesity can lead to heart disease, but when it comes to mental illness, we feel helpless to stem the tide. And so we turn our attention elsewhere, to more “solvable” problems, until the next time that mental illness takes a victim and makes headlines.

The good news is that this perspective is woefully out-of-date. Psychiatry and neuroscience have made incredible advances in recent years toward understanding the root causes of mental illness. We now know the debates about “nature vs. nurture” are over. The winner, resoundingly, is both.

Some mental illnesses clearly result from the intersection of inherited genetic vulnerabilities and the burdens of painful and tragic life experiences. This isn’t true of every illness or every case, but in order to make progress in decreasing the number of serious mental illness cases, we’re going to have to understand the way that childhood trauma interacts with genes in our developing brains.

Childhood trauma can take many forms, including loss of parents, abuse both within and outside the home and bullying in schools, among others. Childhood trauma doesn’t just leave bad memories, it actually damages the structural and biological functioning of the brain. To understand this, we have to appreciate how much the brain continues to develop after birth. By way of contrast, when children are born, their hearts are ready to immediately start effectively pumping blood. Yet the brain is only partially developed and still a long way from being able to do its job independently. That’s why we rely on so much parental care for so many years until we’re ready to operate on our own. Fortunately, when families and communities are functioning as supportive and protective holders of children, one critical outcome is healthy brain development.

One of the important aspects of brain development is our stress-response system. This has been an incredibly productive area of neuroscience research in the past few decades. When we are faced with a threat or a significant stress, the Hypothalamic-Pituitary-Adrenal (HPA) system is called into action, ultimately leading to the release of cortisol. (Cortisol is our primary stress hormone, and it has important effects on virtually every organ system — brain, cardiovascular, immunologic and more.) These effects are crucial when we have to be in “fight or flight” mode.

Fortunately, the system has a very sophisticated built-in set of monitors to detect levels of cortisol and provide feedback to the hypothalamus, so that the system can increase and decrease its output in highly sensitive ways. The problem is that we simply weren’t built for our stress-response systems and our brains to develop under conditions of trauma or neglect. Chronic stress in childhood — and especially unpredictable and traumatic stress — leads to all kinds of long-term hyper-reactivity of the system, which in turn impairs brain development. For example, childhood abuse results in stunted growth of the hippocampus, a crucial brain region that supports memory and learning.

These stresses actually can begin during pregnancy. Stress in pregnancy can lead to offspring with HPA hyper-reactivity and problems with immune function and attention. Some researchers suggest that domestic violence is a particularly toxic stress: It may impact a baby’s brain development in utero, then again when infant care is compromised by the mom’s stress and depression and a third time by direct exposure to a violent atmosphere.

Many studies have now demonstrated that traumatic experiences in childhood result in greater risk of suicide years later; the more numerous and severe the trauma, the greater the increase in suicide risk.

So how does it work that a bad experience in the distant past would be contributing to a suicide in the present? We are accustomed to thinking of genes in a simple model — you either have a gene that causes a disease, or you don’t, and the genes we have don’t change their activity during our lives. But we’ve learned that it rarely works that way. Genes aren’t merely blueprints that design us during pregnancy and then stop working. One of the most exciting areas of research in recent years has been “epigenetics,” which studies the process by which genes are turned on and off. Many of our genes continue to work throughout our lives, instructing our cells to build specific proteins that are needed for different kinds of functions. So, the task of turning on and off the productivity of those genes appropriately is just as critical as the combination of genes that we’re born with.

In numerous laboratory studies, genes that control cortisol are found to be directly altered by the recurrent stress of unexpected maternal separations, resulting in “epigenetic” modifications to specific genes that are involved with the cortisol system. These modifications result in lifelong overactivity of the stress-response system. This presents a great risk of helplessness and despair in the offspring and measurable distortions in the growth of brain structures. And it doesn’t stop with that generation. The modification of the gene is passed on through several generations — even when those later generations didn’t experience the traumatic events themselves.

Studies have found the same modifications in that cortisol-controlling gene in suicide victims who had a history of childhood abuse. We already knew that childhood abuse leads to changes in brain function and an increased suicide risk, but now we can identify a likely molecular pathway connecting these tragic outcomes. And yet, the situation isn’t hopeless — studies suggest that the quality of parental care can provide powerful protection from the damaging effects of trauma and stress, even to the extent of reversing some of the gene changes described above.

It isn’t just the risk of depression and suicide that is increased by childhood trauma — there also is the risk of schizophrenia. Recent studies show that adults with psychosis are close to three times more likely to have had childhood trauma than the general population. Bullying alone was found to double the risk of psychosis among adolescents. And, once again, the more trauma in childhood, the greater the likelihood of psychosis and the greater the severity of the symptoms. A recent review of all the relevant studies calculated that if we could somehow remove childhood trauma from the equation, we would reduce the number of psychosis cases by a third.

Of course, it’s not as simple as thinking of trauma as “the cause” of schizophrenia, or that all mental illness is really just a post-traumatic condition. Not all cases of mental illness have trauma in the history, and not all experiences of even severe trauma will result in mental illness. Mental illnesses are biologic diseases, and many people become ill primarily because of genetic makeup or other conditions that stress the brain, such as substance abuse. Childhood trauma is only one part of a terribly complex picture. Still, there is ample research indicating that childhood trauma is an important contributor to some of our most crippling and fatal mental illnesses.

So, is there really anything we can do to decrease the prevalence of mental illness if doing so depends on tackling the seemingly overwhelming problem of childhood trauma? As it turns out, the evidence provides more reason for optimism than you might think.

The key seems to be in preventive interventions that are targeted toward protecting children who are at greatest risk, and in adhering closely to interventions that have been studied over time. For example, some of the best-studied anti-bullying programs used by schools can reduce the problem by 30 percent. These programs emphasize reducing bullying opportunities through playground supervision, engaging and educating parents, and firm disciplinary consequences for bullying.

Regarding childhood abuse, one program that has been studied in multiple settings over several decades involves sending nurses to visit first-time pregnant mothers who are at especially high risk due to social and economic disadvantages. The nurses focused on building alliances with the new moms and helping them take control of their own lives, improving prenatal health (such as reducing tobacco and drug use), and teaching parenting skills that center on providing a secure attachment for their new babies and understanding their babies’ needs. Moms who received these interventions had profoundly different outcomes as compared with others in randomized control groups. According to one study, the chances that they would abuse their children were reduced by 80 percent. The women also experienced less alcohol and drug abuse, were arrested less and spent less time on government assistance. And at 15-year follow-up, their kids were 50 percent less likely to have been arrested.

Another highly promising program targeted families in which one of the parents recently died. In a randomized control trial, some families received group sessions for the surviving parents and children that focused on increasing positive coping and decreasing negative thinking. There was a strong emphasis on parenting that provided warmth, open communication and effective discipline. Six years later, the families that had randomly received the intervention had kids with fewer mental problems and more solid self-esteem. Additionally, the kids in the program had less reactive cortisol systems when faced with negative events. In other words, the program resulted in kids who were better able to cope with later misfortune, and this might be due to preventing the kinds of chronic alterations to the stress-response system that we see after childhood trauma.

But can we afford such programs? Providing home visits by highly skilled nurses is not inexpensive. However, when calculated over 15 years, the savings generated by that program (in reduced social services, medical care and criminal justice involvement) were four times greater than the costs. And this doesn’t include the savings — not to mention the human toll averted — of keeping some of these kids from developing depression or psychosis that, in the worst cases, leads to suicide. Suicide alone takes 38,000 lives in the U.S. each year, more than are killed by homicide.

It’s true that we can’t change the genes that put us at greatest risk for serious mental illness. But we now understand that those genes are directly impacted by experience — childhood trauma and deprivation that can result in measurable changes in gene structure and function, which in turn affect the development of the brain.

Fortunately, one of the most impressive discoveries of neuroscience in recent decades is that the brain is a remarkably resilient organ. Its neuronal networks can be damaged and distorted by childhood trauma, but also have incredible capacity to grow and to heal — what neuroscientists refer to as the brain’s “plasticity.” This plasticity also has generated growing optimism about programs that provide intensive psychosocial treatment for patients at the very beginning of a psychotic illness.

When children are traumatized or neglected, the result is a brain prevented from healthy development. It might be years or decades before the visible effects of a mental illness are apparent, and often by that point all we can do is mitigate the damage. But by targeting families at risk, we can make an investment in prevention that holds the hope of freeing some children entirely from a future devastated by mental illness. It would be a shame to have to look back 15 years from now and still find our community facing the same burden of mental illness, having missed the opportunities to prevent those cases that might be preventable.

Adam M. Brenner, M.D., is associate professor of psychiatry and a distinguished teaching professor at the University of Texas Southwestern Medical Center. Reach him at adam.brenner@utsouthwestern.edu.