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This week:

Was It Your Mama or Your MAOA?

Monoamine oxidase-A, co-implicated in mood and behavior disorders.



by David Dobbs
Editor, Mind Matters
Genetics and neuroscience are among biology's most exciting areas partly because they often discover mechanisms underlying long-mysterious behaviors, abilities or traits. The two disciplines are increasingly linked, as neuroscience reveals how intricately the brain's workings depend not just on the brain's genetic activity but also the evolutionary history shaped the brains we live with. The emerging discipline of psychiatric epidemiology has pursued this connection with particular rigor, examining closely the interplay of genetics and environment that produce conditions and behaviors ranging from depression and suicide to antisocial behavior and violence. The most obvious news from these studies, notes psychiatrist David Olds below, is good: because neither genes nor environment alone will likely create serious mental illness, most of us feel pretty good most of the time. The bad news? Many of us carry genetic vulnerabilities for depression or other mental illness should our lives turn grim. How, asks Olds, do such undesirable genes survive the pressures of natural selection? Maladaptation, it seems, is not always so mal.

(Mal)Adaptation and Mental Health:
Is Pathology Always Bad?

David D. Olds, M.D.
Columbia College of Physicians and Surgeons
New York, NY

It is generally accepted that bad parenting leads to psychopathology -- unless the child is "resilient." But which kids are resilient? Those who overcome bad environments. Is this a circular argument or nonsense? Some remarkable findings concerning this question have risen from an emerging interdisciplinary approach known as psychiatric epidemiology. Psychiatric epidemiology combines genetics, epidemiology and neuroscience to investigate how genes and environment affect vulnerability to psychiatric and mood disorders. Last year two of this discipline's leaders, Avshalom Caspi and Terrie Moffitt, reviewed its main findings in Nature Reviews Neuroscience. Their paper, "Gene-Environment Interactions in Psychiatry: Joining Forces with Neuroscience" [see abstract or pdf download of the paper] suggests that the gene may have less of a stranglehold on one's destiny than is often assumed. The paper also raises questions about why so-called maladaptive responses to environment, such as depression or passivity, have survived millennia of selective pressure. Gene, Meet Environment In one of Caspi and Moffit's studies, they set out to discover how reliably the environment of the parent-child relationship predicted future pathology. They followed 1,037 families in Dunedin, New Zealand, evaluating the children every two years from birth until age 26. A sub-group of these children carried a variant of a gene coding for monoamine oxidase-A (MAOA), an enzyme that plays a key role in regulating neurotransmitters of psycho-neurological import such as serotonin and adrenaline. Another variable within the study population was that some of the children suffered from physical abuse by their parents. The "environment" theory of psychopathology would predict that these maltreated children would become violent abusers themselves. However, it turned out that only those who were abused and had the variant MAOA gene were more likely to become sociopathic and violent as adults; those who were abused but lacked the variant MAOA gene were no more prone to violence that kids who weren't abused. Likewise, those with the variant gene who grew up in non-violent homes were not more prone to violence. Neither gene variant nor environment alone was enough to confer vulnerability; it took both. A separate study of the epidemiology of depression produced analogous findings regarding a genetic variant in a serotonin transporter gene and stressful life events. Depression was more likely if both the gene variant and the stressful environment were present. Again we see that the gene is only partially determinant of the child's future; environment plays a crucial role. How Do "Bad" Genes Last? One implication of these findings is that evolution has been kind to us. Most parents treat their children decently, and most children are born with the "normal" MAOA and serotonin transport genes. So an even smaller minority suffers the double whammy of bad parents and vulnerable variants. But why has Mother Nature -- or natural selection -- allowed these bad genes to persist? The answer to that question may be somewhat disturbing. The "maladaptive response" -- in this case, the sociopathy or the depression described in these studies -- is not maladaptive enough to cause that gene to perish and disappear. Such individuals can survive long enough to reproduce, and that is what determines whether the gene is passed on. Then there's the matter of "phenotypic plasticity," as illustrated by a recent paper from the McGill University lab of developmental researcher Michael Meaney. Phenotypic plasticity refers to the way that individuals may express their genetic profiles differently depending on the environment. Strangely, as the Meaney paper illustrates, certain such changes may rise in offspring because of the environment that shaped the parents. For example, rats appear to have two kinds of parenting. In one kind the dam frequently licks and grooms her pups, and she nurses them with feet apart and her back arched, offering ready access to her teats. The other kind of mother does little licking and grooming and nurses while lying flat so that the pups are pinned down beneath her. Pups in both cases are adequately fed, but those from the first type of dam tend to be more frisky, independent and adventurous. It was previously thought that the two kinds of dams were hard-wired for their type of mothering. But the Meaney lab found that a more nurturing dam subjected to stress would take on the negative pattern -- and would not revert to the more positive style even with subsequent litters. In all cases, the infants from the dams with the less nurturing style showed higher levels of stress hormones and chronic activity in the amygdala, an area of the brain associated with the fear response, suggesting they labored under a chronic sense of fearfulness. A separate experiment with macaque monkeys [pdf download] compared three kinds of environmental influence on nursing mothers. One group of mothers enjoyed easy, certain access to food. A second group had steady access, but only to hidden food that took more time and effort to find. For the third group, food availability alternated on an unpredictable schedule between none and plentiful. The third schedule created the most apparent stress -- and produced offspring that were timid and avoidant as infants, showing signs of depression similar to monkeys who suffer prolonged separation from mothers, and more fearful, submissive and less social as adolescents. They showed permanent tendencies to have higher stress hormones. Adaptive Pathology What are we to make of all this? We must remember that these results refer to probabilities, not absolute causality. For instance, even for the outcome of the double whammy, the less adaptive result is more likely but not certain. Yet it appears that in environments of uncertainty and turmoil, in periods of famine that may last for generations, survival advantage may come from being timid, reclusive, even submissive to tyrants. As Caspi and Moffitt make clear, this research is in its infancy. Future inquiries may help us better understand the personality characteristics of the children of holocaust survivors, of the willingness of traumatized peoples such as the post-Depression and post-World War I Europeans to submit to demagogic despots. How will the children of Iraq, now being traumatized in a terrible civil war, adapt to the world of the next generation? In clinical practice we see the results of many different kinds of parenting. I've long believed that child abuse or neglect leads to pathology as naturally and inevitably as a bump on the head produces a goose egg. But these research results imply that things are more complicated. The "maladapted" child of the abusive parents may be carrying out the enacted and unconscious injunction of those adults: "Life is terrible, and we may be near extinction; watch out, lay low, and do whatever you can to survive and keep our kind from dying out." David Olds teaches clinical psychiatry and psychoanalysis at Columbia University and is an editor of the journal Neuro-Psychoanalysis.. He has written often on the relationship between neuroscience and psychotherapy.