FPR-UCLA 4th Interdisciplinary Conference - Summaries

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Session 1 Summary: Current Neuroscientific, Clinical, Cultural, and Historical Perspectives on Psychiatric Disorder

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. 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. 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 8) 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.


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