Session 1. Current Neuroscientific, Clinical, Cultural, and Historical Perspectives on Psychiatric Disorder
Epigenomic Mediation of the Impact of Early Life Social Environment on Adult Mental Health
Moshe Szyf, PhD, Department of Pharmacology and Therapeutics, McGill University
The programming of the genome is accomplished by the epigenome. Two elements of epigenomic control are chromatin modification and DNA methylation. Epigenetic patterns are generated during cellular differentiation by a highly programmed and organized process. Nevertheless, they are dynamic and responsive to the environment especially during the critical periods of gestation and early life as well as later in life. This sensitivity of the epigenetic machinery to the environment offers a conduit through which the environment can sculpt the genome and have a long-term impact on behavior. We will discuss three studies from rat, rhesus monkeys, and humans delineating the signature of maternal care and social adversity on the epigenome. We used high-density oligonucleotide microarrays combined with methylated DNA immunoprecipitation to map the response of the “methylome” “acetylome” and “transcriptome” in different brain regions as well as T cells and whole blood in adults exposed to social adversity early in life and controls. Our preliminary results indicate a wide signature of early life maternal care and social positioning on the methylome. Our data also suggest evolutionary conservation of the response and its co-clustering in defined genomic regions.
The Clinician’s Point of View: How a Psychiatrist Can Accurately Predict the Future after it Happens
J. David Kinzie, MD, Oregon Health and Science University
The speaker will present a case study and family from Somalia and discuss it in terms of threshold, context, and trajectory. The presentation will include a brief video of the interview and information about the family.
Session 2. Cultural and Biological Contexts of Autism
Culture and ASD: The Impact on Prevalence and Recognition
Roy Richard Grinker, PhD, Department of Anthropology, The George Washington University
The current state of research on autism prevalence and diagnosis is described from a global, cross-cultural perspective. While knowledge about autism is increasing rapidly throughout the world, there are to date few scientific studies of the characteristics, prevalence and phenotypes of autism spectrum disorders outside of North America and Western Europe. Socio-cultural factors in both developed and developing countries influence autism research, especially epidemiology. Other topics to be covered include: the role of culture in developing interventions and services, conceptualizing autism as a disease vs. a disability, the role of language in screening and diagnosis, social stigma, and urban-rural differences in autism awareness. It is argued that understanding autism as a cultural phenomenon, and as a disability, may lead to better prevalence estimates, and better services and community integration of people on the autism spectrum.
The Neural Development Defects that Lead to Autism
Eric Courchesne, PhD, Department of Neuroscience, University of California San Diego School of Medicine
Although the neurobiology of autism has been studied for more than two decades, the majority of studies have examined brain anatomy 10 or more years after the onset of clinical symptoms. The early neural defects that cause autism remain unknown, but their signature is likely to most evident during the first years of life when clinical symptoms are emerging. This lecture highlights new neurobiological findings during the first years of life and places evidence on older autistic subjects in the light of these discoveries about the early brain growth pathology in autism. Three phases of brain development pathology in autism are theorized: a phase of early brain overgrowth, then arrest of growth and finally degeneration in some percentage of cases. Early brain overgrowth may be a key to discovering the neural bases for emergence of autistic behavior as well as its genetic and non-genetic causes. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Since large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations in autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional and communication functions that epitomize humans.
The Fetal Testosterone Theory of Autism
Simon Baron-Cohen, PhD, Autism Research Centre, University of Cambridge
Autism affects males much more often than females. The explanation for this must either lie in diagnostic practice, hormones, or genetics, or a mix of all three. In this lecture I summarize work from our lab from three lines of investigation: (1) The role of fetal testosterone (FT) in later social and communication development, and in the development of autistic traits. The study uses amniocentesis, the timing of which coincides with the surge in FT production, and is a longitudinal follow-up of typically developing children. (2) The evidence for hormone dysregulation in autism. This includes evidence from the timing of puberty, and the association with testosterone-linked medical conditions in autism. (3) The association between candidate genes that regulate testosterone, and autism. These three lines of research suggest FT is a key factor underlying social development and may play a part in autism. Converging evidence for the link between testosterone and autistic traits comes from rare medical conditions where FT is elevated (such as Congenital Adrenal Hyperplasia). The discussion ties these different lines of evidence together.
Baron-Cohen, S. Lutchmaya, S, & Knickmeyer, R, (2005) Prenatal testosterone in mind: Studies of amniotic fluid. Cambridge, MA: MIT Press/Bradford Books.
Baron-Cohen, S. (2003) The essential difference. New York: Basic Books/Penguin.
Baron-Cohen, S. (2009) Autism and Asperger Syndrome: The Facts. Oxford, UK: Oxford University Press.
Baron-Cohen, S., Knickmeyer, R., & Belmonte, M. (2005) Sex differences in the brain: Implications for explaining autism. Science, 310, 819–823.
Chakrabarti, B., Hill-Cawthorne, G., Dudridge, F., Kent, L., Wheelwright, S., Allison, C., Banerjee-Basu, S., & Baron-Cohen, S., (2009) Genes related to sex-steroids, neural growth and social-emotional behaviour are associated with autistic traits, empathy and Asperger Syndrome. Autism Research, 2, 157–177.
Session 4. Cultural and Biological Contexts of Bipolar Disorder
Bipolar Illness: Personal and Professional Perspectives
Kay Redfield Jamison, PhD, The Johns Hopkins School of Medicine
The lecture will describe the phenomenology of manic and depressed mood states, with a focus on the addictive qualities of euphoric manic states and the dangers of dysphoric, mixed ones. The complex problem of non-adherence to medications and the high risk of suicide in bipolar illness, as well as the subjective mood states associated with each, will be discussed. The importance of skilled psychotherapy, in addition to psycho-pharmacology, will be emphasized, as well as the ethical and societal implications of treating an illness that is destructive and life-threatening yet also associated in some individuals with creativity and accomplishment.
Understanding How Functional Abnormalities in Brain Circuitry Relate to Mood
Dysregulation in Bipolar Disorder
Mary L. Phillips, MD, University of Pittsburgh
Identifying neural system abnormalities that may represent objective biomarkers of bipolar disorders is a crucially important step toward the long-term goal of improving diagnostic accuracy of these disorders, and informing management in individuals presenting in the early stages of illness. My research has focused first on employing neuroimaging techniques to identify abnormalities in brain circuitry supporting emotion processing and emotion regulation in adult bipolar disorder that may serve as objective biomarkers to help improve early diagnosis of the disorder. My second focus has been examination of the extent to which neuroimaging can help identify emotion regulatory brain circuitry abnormalities in youth at genetic risk of bipolar disorder, to help provide objective markers that may be used to identify those at risk youth who are most likely to subsequent develop the disorder later in development. I will present findings from neuroimaging studies from my group in which we have employed different neuroimaging techniques, including functional Magnetic Resonance Imaging and diffusion tensor imaging, ,to examine the structural and functional integrity of brain circuitry underlying emotion regulation in healthy, bipolar and unipolar depressed adults. I will present findings from these studies that have abnormalities in this circuitry in people with bipolar disorder that have the potential in the future to be used as objective markers to improve accuracy of diagnosis of the disorder, especially in depressed individuals. I will also present some findings from studies in which we have employed similar neuroimaging techniques and experimental paradigms in youth at genetic risk of bipolar disorder. These findings provide evidence of abnormalities in brain circuitry supporting emotion processing and emotion regulation in offspring of parents with bipolar disorder who range from being healthy and unaffected by psychiatric illness to having diagnosed bipolar disorder. I will discuss the extent to which these brain circuitry abnormalities in at risk youth have the potential to be able to serve as objective markers denoting likely risk of future development of bipolar disorder in these youth through adolescence and adulthood.
Mania and Depression in American Culture
Emily Martin, PhD, Department of Anthropology, New York University
I explore psychiatric categories involving emotion through ethnographic fieldwork in the contemporary US. I ask how these categories are culturally created, measured and applied in relation to gender and race; then modified, contested, and rejected in contexts such as clinical rounds, patient advocacy support groups, and internet newsgroups. Some issues raised include: What definitions of rationality do mood disorders entail? What are the implications for the personhood of the patient of treating “irrational” mood disorders with psychotropic drugs intended to “manage” them? What are the stakes of the current broad revaluing of “mania” for larger cultural contexts, such as competitive US corporations, which now place a high value on energized, "manic" states for the sake of the innovation and creativity they are believed to yield?
Session 5. Cultural and Biological Contexts of Schizophrenia
The Continuum of Psychosis: Cultural and Biological Risks and Benefits
Robert Bilder, PhD, ABPP-CN, Semel Institute for Neuroscience and Human Behavior, UCLA
The more we learn about psychiatric syndromes the more we recognize that these do not fall neatly into discrete categories. Dimensional rather than categorical structures have been suggested for many psychiatric syndromes, including the psychotic disorders. Some theories, supported in part by observations of clinical symptoms observed in the context of systemic illnesses, suggest that all psychiatric syndromes may best be explained by a single severity continuum. There is continued debate about whether schizotypy is better explained as a dimensional construct or as a discrete category, particularly in the healthy adult population, and it remains unclear to what extent research, some of which has been conducted on college students, generalizes to the general population. Further questions revolve around the extent to which schizotypal traits are best conceptualized as liability factors for psychopathology, particularly “schizophrenia proneness”, or may index aspects of cognitive function that have adaptive value. We have been examining performance on the Chapman Scales (Perceptual Aberrations, Magical Ideation, Physical Anhedonia, and Social Anhedonia) with respect to temperament/character traits, divergent thinking (Torrance Tests of Creativity), latent inhibition, a wide range of neurocognitive performance indices, and creative achievement. Results from the Tennenbaum Family Center for the Biology of Creativity show positive correlations for positive schizotypal personality traits (perceptual aberration, and magical ideation) with both lifetime creative achievement and divergent thinking tasks. Additional preliminary data from the Consortium for Neuropsychiatric Phenomics, an ongoing genome-wide association study (GWAS) in a demographically similar community sample, and which also include “negative” schizotypy scales (physical and social anhedonia) suggest on the other hand that higher schizotypy is associated with poorer performance on tests of memory and response inhibition. This presentation focuses on interpretations that may help explain this apparent paradox, and on hypotheses that selected aspects of cognitive flexibility may be associated with both increased positive schizotypy and confer an adaptive advantage, perhaps helping to explain the persistence of genes associated with psychosis despite decreased fecundity. (Supported by the Consortium for Neuropsychiatric Phenomics (UL1DE019580, RL1MH083268, RL1MH083269, RL1DA024853, RL1MH083270, RL1LM009833, PL1MH083271) and the Tennenbaum Family Center for the Biology of Creativity).
Predictors and Mechanisms of Conversion to Psychosis
Tyrone Cannon, PhD, Departments of Psychology and Psychiatry & Biobehavioral Sciences, UCLA
This talk will address recent progress in the prediction of schizophrenia and related disorders, as well as in the identification of genetic and neural mechanisms associated with their onset. In the context of a multi-site study of 291 prospectively followed youth at high clinical risk for psychosis, we have observed a cumulative conversion rate of 35% and a decelerating rate of transition during the 2.5-year follow-up period. Five features assessed at baseline contributed uniquely to the prediction of psychosis, and algorithms combining two or three of these variables resulted in dramatic increases in positive predictive power (i.e., to 68-80%) compared with the prodromal criteria alone. These findings indicate that prospective ascertainment of individuals at risk for psychosis is feasible, with a level of predictive accuracy comparable to that in other areas of preventive medicine. The mechanisms underlying the development of psychosis are not known, but maturational and disease-related changes in the structure and functioning of a number of key brain systems known to be disturbed in schizophrenia, including prefrontal and medial temporal lobe regions, figure prominently in most theoretical accounts. Cortical gray matter reduction in schizophrenia does not reflect a loss of cell bodies, but rather, a reduction in dendritic and synaptic elements that support inter-neuronal connectivity. Here I report the first evidence of a steeper rate of gray matter reduction among clinical high-risk individuals who develop psychosis compared with those who do not. We have also shown that gray matter reduction in the prefrontal cortex and hippocampus, as well as disrupted social functioning and working memory, are related to variations in a known susceptibility gene for schizophrenia – DISC1. In a series of animal transgenic studies, we demonstrate that experimentally altered DISC1 function produces neurons that achieve less connectivity with other cells, produce smaller amplitude responses to electrical stimulation, and produce disrupted behavior paralleling that observed in patients with schizophrenia, including reduced social preference and impaired working memory. These series of studies provide the background for an emerging prevention strategy aimed at early identification of individuals at risk and preventive intervention targeting specific molecules affecting neuronal plasticity and connectivity.
The Center Cannot Hold: My Journey Through Madness
Elyn R. Saks, JD, University of Southern California Gould School of Law
Elyn Saks will narrate the story of her struggles with schizophrenia, punctuating her narrative with passages from her book, The Center Cannot Hold: My Journey Through Madness. Her hope is to give people a window into the mind of someone suffering with psychosis. She will conclude her talk with some of the policy implications of her story, recognziing that she is an "n" of only one.
Shadows and Illuminations
Robert Lemelson, PhD, President, FPR; Department of Psychiatry and Biobehavioral Sciences, UCLA
“Shadows and Illuminations” is an ethnographic film addressing questions regarding how to represent and understand extraordinary experiences that appear to a psychiatric audience as clearly indicative of severe mental illness, yet other, less stigmatizing and more culturally syntonic, interpretations are possible. The film, shot over the course of 12 years in Bali, Indonesia, follows the life course of a older Balinese man, Pak Kreta, as he narrates and struggles with the continuous intrusion into his consciousness of what he terms “shadows”, or spirits. The film documents his painful and traumatic personal history of trauma, loss and exposure to toxins, all of which possibly contribute to his extraordinary experiences. The film also contextualizes Pak Kreta in modern Balinese history and culture, and draws on other family members memories and interpretations of how to understand his struggles and distress. Central questions of how to interpret these experiences, and to what role a psychiatric diagnosis and the meanings such a label entails are explored and implicitly problematized throughout the course of the film. The film also explores the role traditional healing, in rural Indonesia, has in framing and treating such states. The film concludes with a consideration of how Pak Kreta has adapted and adjusted to his spirits, and how he attempts to find a small measure of peace towards the later years of his life.
Session 6. Cultural and Biological Contexts of Anxiety-Related Conditions
Interoception in Psychiatric Disorders: When the Brain Misinterprets Signals from the Body
Emeran Mayer, MD Professor, Departments of Medicine, Physiology and Psychiatry and Biobehavioral Sciences; Director, Center for Neurobiology of Stress, UCLA
Converging experimental evidence has resulted in the current view that subregions of insular cortex and connected brain regions play an important role not only in the encoding and modulation of interoceptive signals, but also in the conscious awareness of feeling states. Evidence from functional and structural imaging studies has in part confirmed the role of interoceptive information from the body proposed by earlier proponents of peripheral theories of emotion. In addition, it has been suggested that anterior insula may mediate behavioral and physiological effects of risk prediction, computing an interoceptive prediction error, between actual and anticipated bodily arousal and homeostatic state. This prediction error in turn can result in a subjective feeling of anxiety as well as associated abnormal states of bodily arousal. The proposed role of the insula as an interface between the body and the mind provides a neurobiological model to explain the close relationship between abnormal body states and emotions.
Culture and Panic Disorder
Devon Hinton, MD, PhD, Massachusetts General Hospital, Harvard Medical School
Panic disorder varies enormously across cultures, in respect to what triggers panic episodes, what is feared, what are the prominent symptoms, and what is done to treat the episodes. I will use Cambodian refugee examples to illustrate this cross-cultural variability. To illustrate how this cultural difference occurs, I will present a model, the multiplex model. According to multiplex model, after a somatic sensation is generated in any of multiple ways, which often involve culturally related processes, the somatic sensations activate multiple types of culturally specific meaning networks. I will argue that somatic symptoms are interpreted according to local understanding of the physiology of the body, and that this has profound impact on what symptoms are feared and the rates and types of panic disorder. I will argue that somatic symptoms have specific metaphoric dimensions, again culturally variable. And I will argue that somatic sensations may activate traumatic memory, which again are culturally variable. These various meanings networks then create feedback loops of fear that may escalate to panic. I will also argue that how persons in different cultures treat panic events varies greatly, and that this is important aspect of the cross-cultural variation of panic disorder. In sum, I will demonstrate that panic attacks are a dimensional construct that can be examined in a sensitive way across cultures. Panic attacks and panic disorder are profoundly patterned by culture: from what somatic symptoms induce panic and how those symptoms are induced, to the meaning and associations to sensations, to what is done to try and gain relief from and treat the panic attack.
Unfamiliar Presentations of Familiar Symptoms in Ethnic Fijian Adolescent Girls: Implications for the Cultural Moderation of Eating Pathology
Anne E. Becker, MD, PhD, ScM. Department of Global Health and Social Medicine, Harvard Medical School; Department of Psychiatry, Massachusetts General Hospital
Eating disorders have recently been identified as a priority area for adolescent mental health care by the World Health Organization. They have global distribution and are increasingly likely to contribute to the burden of illness in populations undergoing migration, urbanization, or rapid economic development. Despite numerous studies documenting how the etiology and phenomenology of body image and eating disturbances are embedded in their local social context, comparatively few studies address the clinical utility of diagnostic criteria for eating disorders when implemented in populations outside of the high-income countries in which they were developed. Ethnographic, clinical narrative, and epidemiologic data from a study of the impact of social transition on eating pathology in Fiji will anchor a discussion and critique of the application of universalizing diagnostic and therapeutic paradigms for eating disorders across culturally diverse populations.
Session 7. Integrating Biology into DSM-V
Animal Models of Mental Disorders
Eric Kandel, MD, Columbia University; Investigator, Howard Hughes Medical Institute
In the last two decades molecular genetics has transformed neurology. Diagnoses of neurological disorders are no longer based only on signs and symptoms, but also on tests for the dysfunction of specific genes, proteins, and nerve cell components as well as brain scans for disturbances of neural systems. Molecular genetics also has led to the discovery of 1) several newly defined molecular diseases caused by mutations in specific genes, such as the channelopathies and 2) new mechanisms of pathogensis such as the trinucleotide-repeat and the prion disorders. To date, however, molecular biology has had only a modest impact on psychiatry. I propose to address this issue by illustrating that whereas neurology has long been based on the location of disease in the brain, there is not a comparable strong neuropathology of mental illness. In addition, tracing the genetic causes of mental illness is a much more difficult task than finding the gene for Huntington’s disease. There is no single gene for schizophrenia, or most other mental illnesses. Most psychiatric disorders have a combined multigenic and environmental basis. As a result of these limitations, psychiatry has not been able to benefit from animal models of mental illness. I will suggest that during the next few years things may change. We also are beginning to know something about the neural circuits affected by these diseases. As a result, we can now develop satisfactory animal models of components of these disorders. I will devote most of the lecture to describe attempts to develop mouse models of memory deficits present in two major mental disorders: 1) anxiety disorders that have a component of learned fear and 2) schizophrenia, focusing on the cognitive symptoms reflected in working memory deficit.
Session 8. Integrating Culture into DSM-V
Including Cultural Variation and Cultural Context in DSM-V
Roberto Lewis-Fernández, MD, New York State Psychiatric Institute; Columbia University; Member, Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic, and Dissociative Disorders Work Group for DSM-V
The phenomenology of psychiatric disorders shows both commonalities and differences across cultures. Cultural groups, for example, may describe psychopathology in more psychological or more somatic terms, or cluster syndromes in alternate ways, connecting symptoms together that other cultures do not acknowledge as related. This diversity can result in syndromes that are distinct from current psychiatric nosology, also known as “cultural syndromes.” Their existence raises several questions: How can this level of cultural variation be included in a universalistic nosology, as represented by DSM-V? What can research on culturally diverse symptom presentations contribute to elucidating the core phenomenological elements of each disorder as well as the socio-biological roots of mental illness? What kind of contextual information can help clarify the relationship between related but diverse presentations of psychopathology? This talk will illustrate an approach for incorporating cultural variation and cultural context in DSM-V by focusing on two cultural syndromes that are related to dissociative symptoms and disorders: ataque de nervios (attack of nerves) and pathological possession. This approach includes the use of cultural information in defining disorder criteria and textual description for DSM-V. It also involves attending to the socio-cultural context of illness expression via a revised Cultural Formulation that can help guide clinical assessment and treatment planning.
Ethnographic Case Study
Tanya Luhrmann, PhD, Stanford University
The talk focuses on the challenge of interpreting hallucinations within the current DSM framework. I begin by discussing apparently non-pathological hallucinations, which are far more common than many imagine; those who experience them could not be diagnosed with psychosis, but the awkwardness they present to the diagnostic nosology is that it is not possible to rule out psychosis when a hallucination is present. Within the system, hallucinations are presumed psychotic. I then move on to discuss the possibility that the way in which hallucinations are understood psychiatrically may affect the way in which individuals experience pathological hallucinations. My case study concerns a young man who meets criteria for schizophrenia, and who hears frequent distressing voices. His voices seem to disappear when they are treated as being meaningful. The case supports the emerging argument that distressing hallucinations may have different pathways from other symptoms of psychosis. It suggests powerfully that the biomedical interpretation of distressing voices may be costly to those who struggle with them.