Stress and the Social Brain

This is just a quick post to mention that our Formative Experiences co-editor – child psychiatrist Daniel S. Schechter of University of Geneva and Columbia University – is giving a talk on “Traumatic stress and mothers’ capacity to engage in mutual regulation of emotion with their very young children” as part of a symposium on “Stress, the Social Brain, and Psychopathology,” which will take place on March 14–15, 2011, in Lausanne, Switzerland. The meeting is hosted by Carmen Sandi’s group, the Laboratory of Behavioral Genetics, which is part of the Brain Mind Institute (École Polytechnique Fédérale de Lausanne).

For all of us who can’t make the conference, Dan has a terrific, comprehensive  essay featured in the February edition of  Cerebrum, a Dana Foundation publication, on “Forecasting aggression: Toward a new interdisciplinary understanding of what makes some troubled youth turn violent.”

Finally, a video of Bruce McEwen’s more general talk, “Neuroscience perspectives of stress and brain and body health: Importance of the social environment,” which he gave at the inaugural conference of the Society for Social Neuroscience, is available at the site.

FE Co-Editor and Swiss Colleagues Awarded Grant on Synaptic Bases of Psychiatric Disorders

We are very pleased to announce that child psychiatrist Daniel Schechter, co-editor of our recent volume Formative Experiences, is one of a group of principal investigators (PI) in Geneva, Switzerland, whose research will benefit from the largest Swiss National Science Foundation biomedical center grant ever awarded. The inter-institutional center is focusing on the Synaptic Bases of Psychiatric Disorders.

Dan is PI of the Infancy and Early Childhood Stress and Development Lab at the University of Geneva Hospitals and Faculty of Medicine, which is studying the impact of maternal interpersonal violence (IPV)-related traumatic stress on the mother-child relationship during formative development of emotional regulation in the following domains (with attention to phenotypes that cut across these domains): psychological, behavioral, physiologic, and maternal neural activation.

The project also aims via a longitudinal design over 2–3 years to identify predictors related to children’s development of a greater tendency toward aggressive versus avoidance/withdrawal behavior by examining individual differences in the following domains: psychological, behavioral, physiologic, genetic/epigenetic.

Dan’s project is part of a 4-year, CHF 17.5 million (US$ 10 million) National Centre of Competence for Research (NCCR) grant awarded to the Federal Institute of Technology, Lausanne (EPFL) and the Universities of Geneva and Lausanne (Pierre Magistretti, EPFL, is the Center’s Director). The Swiss federal government has been supporting NCCR research networks since 2000. The program places particular emphasis on interdisciplinary approaches and new, innovative angles within the individual disciplines.

Link to the Swiss government press release:

Cultural and Biological Contexts of Psychiatric Disorders / Opening Session (FPR-UCLA Jan 2010 Conf)

We will be periodically posting summaries of the 4th interdisciplinary conference on brain, mind, and culture (“Cultural and Biological Contexts of Psychiatric Disorder”) sponsored by the Foundation for Psychocultural Research and UCLA, which took place at UCLA on Jan 22-24, 2010. Below is the summary for the opening session:

Session 1 Summary: Current Neuroscientific, Clinical, Cultural, and Historical Perspectives on Psychiatric Disorder
Participants in this session discussed the biological, clinical, cultural, and social dimensions of psychiatric disorder. The session was chaired by UCLA neurobiologist Marie-Francoise Chesselet. Speakers and commentators included UCLA vice-chancellor Claudia Mitchell-Kernan, UCLA anthropologist and FPR president Robert Lemelson, Dr. Chesselet, Harvard anthropologist Byron Good, McGill epigeneticist Moshe Szyf, OHSU trauma psychiatrist J. David Kinzie, and Stanford anthropologist Tanya Luhrmann.

In her opening remarks, UCLA’s Vice-Chancellor of Graduate Studies Claudia Mitchell-Kernan noted the timeliness of the conference, which focuses on the cultural and biological contexts of psychiatric disorder and precedes publication of the DSM-V in 2013. “I think a good deal is at stake,” Dr. Mitchell-Kerman said. “The diagnostic criteria established in the fifth edition will in many ways establish how society views various forms of emotional and psychological conditions, and, just as important, what kind of treatment is available and what kind of access insurance programs will offer.”

“The current focus on culture, the brain, and mental illness,” FPR founder and UCLA anthropologist  Robert Lemelson said in his opening remarks, “is one that is certainly close to my interests and my heart. I’ve been studying this topic for the last two decades in Indonesia, [and it’s one in which] biology, culture, history, and political economy all play central roles.” One of the objectives of the conference, he continued, is to highlight the intersection of culture, biology (particularly neurobiology) and social and political ecologies in the origin, presentation, and outcome of mental illness. He quoted from a critical article that appeared in the New York Times Magazine; the article by Ethan Watters is based on his book, Crazy Like Us, and concerns the export of a DSM-based framework for categorizing and treating mental disorders across the globe. Although, based on his fieldwork in Indonesia, Dr. Lemelson has found that such a biologically based model can be useful at times in dispelling “prescientific myths and harmful stigma,” he noted the extent to which (directly quoting from Ethan Watters) “in the process of teaching the rest of the world to think like us, we’ve been exporting our own western symptom repertoire as well.” (This theme recurs throughout the conference and is highlighted in particular in the last roundtable session on Day 3.)

Interdisciplinary Foundations

Introductory remarks to the first session of this conference were presented by UCLA’s department of neurobiology chair, Marie-Françoise Chesselet, who studies the basal ganglia, with special focus on Parkinson’s disease. “When we were trying to conceptually frame this conference,” she said, “a discussion erupted about the broadness of psychiatric illnesses versus the more focused definition people have of neurological disorders.” During that discussion, as well as in her opening remarks, Dr. Chesselet used Parkinson’s as an example of a neurological disease for which there was once a very “reductive” (in the positive sense) explanation, what biological psychiatry now strives for vis-à-vis mental disorders. In the case of Parkinson’s, the disease is now best conceptualized as a complex, multi-dimensional condition. (As will be highlighted in later sessions, most of the mental disorders are now presumed to have similarly complex neurobiological etiologies.) Long considered to be a disease of the dopaminergic neurons with a well-defined set of motor disorders, she explained, Parkinson’s is now understood to involve almost every area of the brain, as well as the peripheral nervous system, and to affect many aspects of psychological functioning. “Now that we know that all those other brain regions are affected and that rather than being a disease of cell death, it is a disease of dysfunction of many circuits in the brain,” she said, “neurologists [have become] a lot more attuned to the patients’ predicament, which goes well beyond the narrow list of symptoms that were used to recognize and treat.” Although psychiatric symptoms are now considered to be a major component of the disorder, culture has yet to be integrated, just as culture has yet to be considered a major component in western psychiatric nosology.

Parkinson’s is a good model for a more holistic way of thinking about mental illness in terms of core concepts such as dimensions, trajectories, thresholds, and the daily predicaments in which persons find themselves. The latter, in particular, was addressed in the next talk, “Cross-cultural research on mental illness and its treatment,” by Harvard psychological anthropologist Byron Good. Dr. Good began by stating a “classic” argument: biological advances alone are not sufficient “to close the gap between what we can do and what we actually do in caring for most persons with mental illness”; this goal is only achievable “by re-conceiving psychiatry as a social and behavioral science and by taking a social medicine approach.” In response to a reductionistic view of psychiatry as “clinical neuroscience” and psychiatric illness as primarily a biological condition from which one can recover, particularly with pharmacological treatment, he offered a critical perspective on neuropsychiatry: on the one hand, the medications we use to treat most psychiatric conditions are crude, inadequate and often dangerous; and on the other, most people worldwide who suffer from conditions that can be treated are not being treated at all. From a clinical treatment perspective, most people worldwide endure the same immiserating conditions that prevailed 25 years ago: “the stigmatizing effects of psychiatric labels, the demoralizing effects of hospitalization, rampant unemployment, poor income supports and a lack of meaningful activity, inadequate housing, and debilitating social isolation” (Mental Health Recovery Study Working Group, 2009). But Dr. Good also provided reasons for optimism. For example, “the great myth of mental illness, and in particular psychotic illness, is that people don’t get better,” he said. “The truth is, a vast proportion of them do.” Concomitantly, he said, there have been major advances in the basic neurosciences and genetics, as well as the publication of rich, ethnographic accounts and cross-cultural research on questions not approachable 25 years ago. “We have important models for research on brain–social environment interactions … as well as a significant number of genuine international collaborations  … where one can begin developing really long-term working relationships with people who are no longer simply functioning (as research assistants) but as genuine collaborators, often taking the lead and leaving us far behind.” The potential for genuine cross-disciplinary, cross-cultural comparative research and new conceptualizations of mental illness is possible, he continued, only if certain developments occur: (1) psychiatry is recognized as a behavioral science; (2) new frameworks allow for sustained collaborations across various dimensions from biology to culture; (3) anthropologists on the one hand and clinicians, neuropsychologists, and biologists on the other seriously engage in cross-cultural research; and (4) improved care is a primary objective. Critical to this framework are anthropologists who provide rich, phenomenological data (including deep analyses of semantics and sociolinguistic context) linked to clinical and neurobiological research and set “within extraordinarily diverse systems of care,” which also link to successfully providing effective care. Deep research on phenomenology or “lived experiences” challenges the conventions and practices of Euro-American psychiatric science. For example, both Dr. Good and Tanya Luhrmann (in Session Eight) described situations in which family/community accept the subjective reality of, engage with, and in many circumstances seem to tame the distressful voices that one person’s psychosis may evoke. Schizophrenia is heterogeneous genetically, etiologically, symptomatically, and in terms of outcome across the globe. One fundamental research question is how cross-cultural research can help clarify its phenotypes (and help determine what role phenotypic differences among individuals play in recovery). To conclude, Dr. Good said efforts should focus on trying to solve real-world problems (and learning from that process) rather than on observation alone. He said the biological view of mental health provides a limited understanding of human conditions, but that meetings such as this one, which bring together scientists, clinicians, and field researchers from different disciplines and cultures, have the potential to build an alternative basic science of psychiatry.

Notable in Dr. Good’s talk was his challenge to anthropologists to link their research to neurobiology. It was fitting in many ways that the next talk was presented by a molecular biologist whose research links molecular mechanisms to the social environment! In his introduction, Dr. Moshe Szyf, of McGill’s department of pharmacology, described his research on the biology of cancer, which he considers a “systemic,” rather than a molecular and cellular, disease of humans who live in particular physical, biological, and social environments. This perspective has provided the basis for his thinking about the effects of early life environment on mental health. Given the physical segregation of disciplines at most institutions, he humorously described how a chance encounter in a Madrid bar with McGill experimental psychologist Michael Meaney led to a theory that the transgenerational effects of maternal care that Dr. Meaney and colleagues had observed were produced via an epigenomic mechanism. In the course of this research, Dr. Szyf came to the astounding realization that “behavior is a vector of inheritance … probably as or more important than the germline.”

“Epigenetics” refers to the various mechanisms in the cell’s nucleus that control genetic activity without altering the DNA sequence. Simply put, if DNA, which is the same in every cell of our body, is the code, epigenetics is the program that controls the local expression of genes in different tissues at different developmental stages. Two mechanisms of epigenetics are chromatin modification and DNA methylation: Dr. Szyf’s talk primarily focused on the latter, which involves the introduction of methyl groups (CH3) that are genetically deactivating onto cytosines in the DNA itself. The methylation pattern was once thought to be unidirectional and highly stable, that is, held constant in DNA replication throughout a lifetime. But as a graduate student, Dr. Szyf wondered about this physiological stability, which runs counter to the universality of reversible reactions in biology, “which creates the flexibility of animal and human life.” After years of research, Dr. Szyf and colleagues found that epigenetic patterns are reversible and that animals that had received little in the way of maternal care and had consequently been programmed to anticipate a certain environment could be phenotypically converted (in terms of stress response), suggesting that the epigenome should be viewed in a state of “dynamic equilibrium,” one that is highly sensitive to environmental influence. In human studies, observing methylation patterns based on hippocampal samples from suicide victims, Dr. Szyf and colleagues found that those who had experienced childhood abuse showed a much higher degree of methylation of the exon 1F promoter of the glucocorticoid receptor (which cortisol binds to) than non-abused suicide cases. (This finding accords with the literature on major depression and its association with cortisol levels.) Further research indicated “that the signature of the mother in the genome is widespread…. There is an entire rearrangement of the chromatin,” supporting the idea that this is a genomic response, rather than one limited to a single gene. The final human study he described, based on a 1958 British birth cohort, investigated the effects of early childhood adversity on DNA methylation and discovered “a very clear signature of the methylation pattern that reflects early childhood socioeconomic status.” An important implication of a “life-long dynamic epigenome,” he concluded, is the suggestion that there are critical or sensitive periods in early life during which epigenetic patterning will have a major long-term influence on health and behavior, underscoring the significance of early interventions.

Trauma psychiatrist J. David Kinzie of Oregon Health and Science University presented the perspective of a cultural psychiatrist who primarily treats refugees living in the U.S. who suffer from PTSD (and very often co-morbid medical conditions such as hypertension). Dr. Kinzie presented a case study of an unemployed Somali man, who had severe PTSD and depression based on his experiences in 1991–1992 during the Somalia civil war and then living for ten years in a Kenyan refugee camp. After an initial 1.5 hr interview, Dr. Kinzie prescribed therapy and medication (fluoxetine and clonidine). Follow-up was erratic, but over time Dr. Kinzie learned that his client was not taking the medication as prescribed, that his 3rd (employed) wife had experienced multiple traumas of her own in Somalia and Kenya and was constantly angry, and that their two children (aged 9 and 12) both suffered from severe ADHD (the wife and children were also being treated at Dr. Kinzie’s clinic). The case, Dr. Kinzie said, exemplifies the changing nature of treatment (as information about context changes or accumulates) and the difficulty in predicting trajectory as persons continuously interact with their environment as well as experience new traumas that re-activate symptoms.

Dr. Kinzie offered four rules of thumb for clinicians to consider: (1) both simple and complex formulations of complex psycho-social-cultural clinical problems are usually wrong; (2) there is no single context or threshold; clinical situations are dynamic and changing and the treatment needs to change in response; and (3) in such a dynamic clinical setting, it is not possible to accurately predict trajectory. He concluded by saying that the optimal clinical approach to psycho-social-cultural disorders is to treat on the basis of known information and patients’ needs, but to modify the formulation and treatment plans a more information is available.

Stanford psychiatric anthropologist Tanya Luhrmann began her commentary by focusing on two “big ideas that speak to the issue of culture and diagnosis” raised in the Ethan Watters NYT Magazine article: (1) the biomedical model is not always helpful for people who struggle with mental illness. Although many hoped that the biologization of psychiatry would reduce stigma, it is clear that the “broken brain” metaphor for schizophrenia is often stigma-generating rather than reducing; and (2) “the way we conceptualize an illness affects the way its symptoms are expressed and experienced.” She said that it is “now clear that (schizophrenia) has a different course and outcome in different countries,” and it is “probably clear that there is a different symptom expression among different groups of people.” Increasing, she said, good psychiatric anthropology research will involve multiple methods, including rich phenomenological analysis accompanied by epidemiological and psychological research, which includes posing structured questions “in ways that can be comparative across multiple contexts.”

The broad inference from the morning talks, Dr. Luhrmann said, “is that it might be more accurate to think of psychiatric syndromes (with multiple moving parts) than of discrete psychiatric illnesses.” However, the fact that the DSM is categorical has limited the kind of research done on illness experience. The roundtable continued this discussion, with Dr. Szyf confessing he does not like the term “mental disease.” Instead, he prefers more neutral language that reflects the notions that mental behaviors are manifested as varied responses in different contexts, including that of culture. The challenge is to determine when the responses are maladaptive. Dr. Good acknowledged the complexity of early life environments and the need for researchers and clinicians to evolve in terms of their own understandings and responses to others’ predicaments, preferably through long-term longitudinal work. Dr. Luhrmann agreed on the value of such research, but said it was very hard to do. She said David Kinzie’s presentation “illustrated beautifully the way in which individuals sneak out of systematic categories.” On the other hand, she said, systematic comparison “really teaches us something that we don’t learn in any other way” and that while such research is difficult, it is crucial.” Dr. Kinzie reiterated that the DSM, while categorical, serves as “a shorthand for communication.” The job of the anthropologist, he added, is to help the clinicians; but to be effective, a coherent management of data is necessary (as well as a structural framework that helps organizes the affect that floods the clinician treating victims of multiple trauma). For Dr. Kinzie, the DSM serves this purpose. One major implication of this session, however, was that a system of social services must be part of the larger academic-clinical structure, particularly in view of the persistent biological effects of early life environment. As an audience member pointed out, achieving this integration requires a long-term focus on parenting, education, and cultural values. Such a change involves vast ethical, legal, and economic issues necessitating discussion and debate not only within the clinical and academic communities, but in the larger society.