Living Under the Description of Bipolar Illness: Neuroscientific Promises and Experiential Reflections

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 our session on bipolar illness.

One innovative aspect of the FPR-UCLA conference was the inclusion of transdisciplinary and experiential reflections on mental health and illness. Saturday morning’s session on bipolar illness (BPI), chaired by UCLA anthropologist Douglas Hollan, focused on white matter tract abnormalities and the possibility of using this neuroimaging finding as a biomarker to differentiate BPI from unipolar depression, as well as to identify persons at risk. Cutting-edge neuroscience was combined with insights from individuals “living under the description of bipolar disorder” (in the words of conference participant Emily Martin). As another conference participant (cultural psychiatrist Laurence Kirmayer) put it, these commentaries “provided grounding and reflection on the limits and promise of current psychiatric theory and practice.”

Neuroscientist Mary Phillips of University of Pittsburg discussed the clinical implications of brain imaging studies detecting abnormalities in neural systems for emotion regulation in BPI. BPI is one of the ten most debilitating illnesses worldwide, with a high (15%) suicide rate. At the same time, BPI is frequently misdiagnosed as unipolar depression (UD). A 2003 study by Hirschfeld and colleagues indicates that only 20% of people living with BPI received a correct diagnosis within the year of first consultation, while 35% did not receive a correct diagnosis for 10 years or more, primarily due to overlap of BPI symptoms with those of other psychiatric disorders. The goal of Phillips’s research is to improve diagnosis by identifying biological markers (e.g., abnormal amygdala activation) that can distinguish BPI from other disorders, including UD, and to identify asymptomatic young persons who may be genetically at risk for developing BPI.

Brain imaging research has identified specific brain circuits by testing voluntary and involuntary emotional regulation in response to facial expressions. Involuntary emotional response processing occurs largely in communication between the amygdala, which detects emotionally salient stimuli, and the orbitomedial prefrontal cortex OMPFC, which regulates emotional responses. Voluntary emotional response processing involves the above areas, as well as the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortices.

A key white-matter tract linking the amygdala to the OMPFC is the uncinate fasciculus. (White matter refers to the white myelin that covers the axons of neurons.) In individuals with BPI, a 2008 study from Phillips’s group using diffusing tensor imaging (DTI), which measures the diffusion of water in white matter tracts, showed abnormal left and right fiber alignment in these circuits. With respect to healthy controls, individuals with UD display abnormal left-side connectivity. However, individuals with BPI display both abnormal left (more streamlined) and right (more diffused) connectivity. In response to happy and sad faces, individuals with BPI show particular discrepancies in left and right connectivity between the OMPFC and the amygdala. The OMPFC’s regulatory effect (“the brake”) on the amygdala is diminished in BPI individuals’ responses to happy faces, particularly on the left, whereas connectivity between these two structures is enhanced in the same individuals’ responses to sad faces, particularly on the right. A further whole-brain study by Phillips and colleagues recruited two groups of currently depressed individuals: those diagnosed with BPI and those with UD, as well as a group of healthy controls. They found significant differences in the right uncinate fasciculus between individuals with BPI, those with UD, and healthy controls. In terms of bidirectional connectivity (using the happy faces paradigm) Phillips’s group found evidence indicating a significant discrepancy between individuals with BPI and those with UD in response to happy faces. Whereas UD individuals displayed greater inhibitory (left OMPFC to amygdala) effective connectivity relative to controls, BPI individuals displayed less with respect to controls, as well as less right bottom-up (amygdala-OMPFC) connectivity than controls.

The structural, functional, and white matter differences in UD and BPI (particularly the “disconnectivity” in BPI vs. the greater inhibitory connectivity in UD) suggest distinct physiological processes underlying the two disorders, which are difficult to distinguish clinically. Phillips’s work presents the serious possibility of one day using objective biological markers for BPI in children who are genetically at risk as well as adults living with the illness, which could eliminate much human suffering due to misdiagnosis, but with all the ethical, social, legal, and mental health policy implications that such an advance would entail.

Kay Redfield Jamison, professor of psychiatry at Johns Hopkins University and author of An Unquiet Mind: A Memoir of Moods and Madness, spoke eloquently and movingly about the personal experience of living with bipolar illness (BPI). Jamison described BPI as a chronic relapsing illness involving “cyclic upheavals” of mania and depression, which she first experienced at age 17. BPI presents a special dilemma since moods are essential to a sense of self, which affects the willingness or motivation to seek treatment (“it’s very hard to tell an 18-year-old, who’s feeling better than he’s ever felt in his entire life that he’s sick”), to stay on medication, and to stay alive. Mild elated states pose a particular set of clinical, theoretical, and scientific problems. She described these states as addictive, at the biological as well as psychological level. Like depression, the manic states (or more generally positive affective states) can be ranged along a continuum, she said, with positive implications for learning, creativity, exploration, and risk taking. (She addressed “the fiery aspects of thought and feeling” in a previous book, Touched with Fire: Manic-Depressive Illness and the Artistic Temperament.) On the other hand, the pain of severe depression and severe mania “are not comprehensible to people who have not experienced them,” a gap she began to address as a young clinician and researcher at UCLA, when she wrote a series of anonymous accounts of her own illness experience for the benefit of the residents and the psychology trainees in the affective disorders clinic.

Jamison movingly described what it was like to have BPI, which she characterized as “recurrent cycles of pain, elation, loneliness, and terror.” She described her unwillingness to accept her illness and take lithium on a regular basis, until repeated psychosis and a nearly lethal suicide attempt convinced “even the slowest of learners.” Although her form of BPI (Bipolar 1 with psychotic features) is well stabilized with medication, she said the illness has a “ghostlike presence,” not only because it can recur but because it can be entwined with a hyperthymic (or “hail-fellow-well-met”) temperament. Psychotherapy may be particularly effective in addressing the erratic flow of experience. Like Elyn Saks, Jamison believes that “psychotherapy has been underestimated in its importance in the psychotic illnesses” and that “it can keep people alive.” Psychotherapy “makes some sense of the confusion, reigns in the terrifying thoughts and feelings, returns some control and hope and possibility of learning from it all. Pills cannot and do not ease one back into reality.”

Supportive faculty at UCLA and Johns Hopkins encouraged Jamison to learn, write, and teach from her own experiences and to be public about her illness, which eventually resulted in the publication of An Unquiet Mind. In her concluding remarks she said that, although the book was initially about illness and moods, it is also about love’s capacity to move, nourish, and sustain her through life’s dark moments.

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Surviving Severe Mental Illness in the US and Indonesia

This summary is by science writer Karen A. Frenkel. Karen will be contributing a blogpost about her forthcoming interview with neuroscientist Martha Farah of the University of Pennsylvania on Dr. Farah’s new edited volume Neuroethics: An Introduction with Readings (MIT, 2010), which includes contributions by Steven Hyman, Eric Kandel, and Peter Kramer.

The 4th interdisciplinary conference on brain, mind, and culture sponsored by FPR and UCLA conference featured a panel devoted specifically to schizophrenia. Elyn Saks, Associate Dean and Professor of Law, Psychology, and Psychiatry and the Behavioral Sciences at the University of Southern California Gould Law School, spoke about her experience living with schizophrenia and her treatment, which combined medication and psychodynamic therapy. She has documented her journey in her book The Center Cannot Hold: My Journey Through Madness (Hyperion Books, 2007). Kay Redfield Jamison, Professor of Psychiatry at the Johns Hopkins University School of Medicine and Honorary Professor of English at the University of St Andrew commented briefly about her experience with bipolar disorder. Also an author, she wrote An Unquiet Mind: A Memoir of Moods and Madness (Vintage, 1997), which details her experience with the ebbs and flows of severe mania and depression.

During the discussion that followed, Dr. Eric Kandel, Nobel Laureate and Professor of Biochemistry and Biophysics at Columbia University College of Physicians and Surgeons, remarked on the similarity of Saks’ and Jamison’s experiences. He said that psychotherapy for severe mental illness is surprising because it is now downplayed, and that psychoanalysis for schizophrenia is “practically unheard of.” He commented, “Obviously it’s a combination of things that is important.”

Saks acknowledged that some experts espouse neither psychodynamic nor psychoanalytic therapy for schizophrenia, but said, “I’m here to tell you that it is (effective) for some people.” Stress is bad for all illness, in particular mental illness, she said, and it is important to understand triggers and learn to cope with or avoid them.

Refusing medication is resistance that arises from the narcissistic injury of having that illness, she said, and working through those feelings of “damage and defectiveness is really important” for recovery. For her, a safe place to bring frightening thoughts (and, as a result, not express them in the workplace) was very valuable. “Interpretations can detoxify symptoms, but not always,” she elaborated. Some believe psychotic symptoms are just random firings of neurons and others think they’re meaningful, Saks acknowledged, but when the person is experiencing them interpretations do not always help.

Having someone accept you not only for the good, the bad, and the ugly is “enormously empowering,” she said. Schizophrenics are people, too, she said, “we have relationship issues and work issues that can be addressed through psychotherapy.” Therapy improves quality of life, she said, “so on lots of different vectors it could be a very helpful compliment to medication.” Although early studies did not involve medication, Saks suggested that future studies explore the efficacy of both psychotropic medication and good, intensive therapy.

Kandel then noted that both women are highly intelligent, which is a sign of ego strength, and asked them to elaborate on their experiences. Jamison responded that intelligence is not always an advantage. Some literature suggests that early on the highly intelligent commit suicide because of their keen awareness of their unraveling and its implications for their future. She also emphasized that refusing medication is a psychological issue, but has enormous medical implications and the patient’s relationship with his or her doctor is “hugely important.” For Saks, working, thinking, and writing are important. “Whatever intelligence I have has helped me navigate having this illness,” she said.

A member of the audience thanked Saks and Jamison for their courage. He then inquired about the tension between recognizing a biological process that might mediate aspects of disorder with the contrasting notion that willpower can overcome that discomfort. Saks responded, “I don’t believe this has anything to do with willpower. Mine is not the story of willpower, but of one who had enormous treatment resources–great psychopharmacology, a supportive family and friends. It’s not will power, it’s help.”

Robert Lemelson, UCLA anthropologist and documentary filmmaker, added that in Indonesia there is one psychoanalyst for 200 million people who mostly treats foreigners. Pak Kereta (the main character in Lemelson’s documentary, Shadows and Illuminations, which is one of a three-part series) has schizophrenia, according to some models. But only during the last cut did Lemelson begin to view Kereta as having “something like schizophrenia.” His outcome, by most measures, is quite good, Lemelson said, because he is married, has children, and works, despite horrific experiences and major stressors in his life and without the kind of western biomedical interventions being discussed. “One of the points we make in the film is that he’s not labeled . . . we show that people, while they consider it odd, don’t consider it insanity, or madness, or mental illness, so he’s protected by the lack of a biomedical label.”

In another film in Lemelson’s series (Afflictions: Culture and Mental Illness in Indonesia), a woman with Tourrette’s Syndrome also escapes labeling, but those in her midst do see her as mad and she has a very poor outcome because her social world is quite toxic. Some of the factors Lemelson mentioned that effect positive and negative outcomes in rural Indonesia include: labeling and social stigma (or lack thereof), supportive family environments, environmental toxins, and the lack of drug abuse. “So several factors, none of which is specifically psychiatric or biomedical, shape outcomes of severe mental illness,” he concluded.

Finally, Marvin Karno, Professor Emeritus, of the Department of Psychiatry and Biobehavioral Sciences at UCLA, emphasized the importance of “a strong sense of tenacity, resilience under incredible stress,” traits that are “not ordinary,” as very important to positive outcomes. Having worked for many years with persons with schizophrenia and bipolar disorder, he has observed that those with good outcomes possess such traits. “They’re essential to fighting any terrible disease,” he said. He described a five-year survivor of pancreatic cancer who was also a triathelete. “She was just determined that that cancer wasn’t going to kill her and it didn’t.”  He suggested that the trait of resilience ought to be further explored.

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:

http://www.news.admin.ch/message/index.html?lang=en&msg-id=32610=

SZ and BPD: The Importance of Psychotherapy

From Session 5 (Schizophrenia) of the FPR-UCLA 2010 conference on cultural and biological contexts of psychiatric disorder.

Below is a 4 min excerpt on the importance of psychotherapy in treating SZ and BPD, which features conference participants Elyn Saks, Eric Kandel, and Kay Redfield Jamison. We have uploaded the entire 24 min panel to the FPR channel on YouTube.

For those who want to hear more, tune in to Philoctetes Center roundtable discussion with NYU psychiatry department chair Charles Marmar (a previous FPR conference participant), clinical psychologist and psychoanalyst Brian Koehler, NYU director of residency training in psychiatry Ze’ev Levin, and Ira Steinman, author of Treating the Untreatable: Healing in the Realms of Madness.

Talk Summaries: Cultural and Biological Contexts of Schizophrenia (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 session on schizophrenia:

Session 5: Cultural and Biological Contexts of Schizophrenia

Participants in this session discussed the biological, personal, cultural, and social dimensions of schizophrenia. The session was chaired by USC psychologist Steven López. Speakers and commentators included UCLA neuroscientists Robert Bilder and  Tyrone Cannon, Harvard professor of social medicine Mary-Jo DelVecchio Good, UCLA anthropologist and documentary filmmaker Robert Lemelson, Caltech neurobiologist Paul Patterson, and USC law professor Elyn Saks. A trailer of Rob’s film, Shadows and Illuminations, is included in this post.

In his opening remarks, session chair Steven López, USC psychology professor and member of the FPR Advisory Board, reflected on the implications of previous day presentations by Moshe Szyf on epigenetics and Eric Courchesne’s work on the putative correlation between early brain overgrowth and autism. “I am seeing the possibility of a shared narrative between those who are doing the neuroscience and those who are interested in the lived experience, in the cultural and the social experience,” Dr. López said. Dr. Szyf’s talk, in particular, provided a sense of the mechanisms through which trauma (or lived experience more generally) can affect brain structure and function (as well as the course of psychiatric disorders). Neuroscientific and cultural narratives may not overlap, but the new work suggests some “potential bridges,” that could lead to a more complete understanding of mental health and illness.

In the first talk, Robert Bilder, head of UCLA’s Consortium for Neuropsychiatric Phenomics (CNP), described psychiatry as suffering from a “flawed taxonomy” due to lack of correspondence between symptoms of disorders such as schizophrenia (SZ) or bipolar disorder (BPD) – on which descriptive phenotypes are based – and underlying pathophysiological or etiological processes. Instead, he suggested that psychiatric syndromes may reflect “quantitative deviation along continuous trait dimensions that merge imperceptibly from ‘normalcy’ into more ‘pathological’ ranges,” with persistence of genetic diversity implying that certain traits (for example, “magical ideation”) have adaptive advantages. Research programs like the CNP are searching for more “biologically relevant quantitative trait (or neuropsychological) phenotypes” that cut across diagnostic groups.

Dr. Bilder discussed two strategies for organizing disorders more systematically in terms of category or dimension – the taxometric and factor analytic approaches, both of which support a non-categorical diagnostic model for most disorders. A review of the DSM based on psychologist Nick Haslam’s review of taxometric studies indicates that certain subtypes of melancholia, social phobia or inhibited temperament in childhood, bulimia nervosa, dissociative identity disorder, and hypnotic susceptibility appear more categorical (i.e., discontinuous or “taxonic” in nature); however all other types of depression, PTSD, BPD, generalized anxiety, and almost all models of personality function (with the possible exceptions of schizotypal personality disorder and antisocial personality disorder) suggest continua. Regarding ADHD, a factor mixture modeling approach indicates two continuous factors (severity of inattentiveness and hyperactivity or impulsivity) rather than “qualitatively distinct ADHD subtypes.” Regarding the categorization of mental disorders as either diseases or syndromes, he said the “prototypical mental disorders” (including SZ, BPD, and anxiety disorders) “merge imperceptibly both into one another and into normality with no demonstrable natural boundaries or zones of rarity in between,” noting at the same time that genetic and environmental factors are “often non specific,” citing work by Kenneth Kendler, Ezra Susser, Alan Brown, and others.

In support of the concept of continua vs. discrete categories for the psychoses, including SZ, he cited neuropsychological evidence indicating that the reliability of a correct classification (as either a functional or an organic disorder) decreased in relation to the increasing severity of the disorder (non-psychotic psychiatric disorders –> BPD –> chronic SZ). A similar correspondence occurred for cognitive deficits, which increased in relation to severity of disorder. On the other hand, he said, there is very little evidence that specific structural brain abnormalities (e.g., ventricular enlargement, gray matter deficits, and hippocampal volume reductions) can be used to distinguish between BPD and SZ, other than in terms of severity. He said the genetics risks are “substantially shared” between the two disorders and that a very large number of genes contribute to both disorders, as reported in a recent study by the International Schizophrenia Consortium. He also said there is likely to be a common set of underlying genetic anomalies that dictate “a whole host” of brain development processes shared across neurodevelopmental disorders,“ and that distinctions may be owing more to severity than to discrete pathology.

Bilder’s team suggests that schizophrenia should also be thought of in terms of degrees rather than kind. Further, drugs are non-specific to syndromes; clinics and insurers (and ultimately patients) are in the “trap” of academia (DSM construction), the government (FDA regulation) and industry (pharmaceuticals that conform to FDA rules). Bilder concluded that a severity continuum of illness is more valuable than categorical taxonomy in understanding the biology of psychoses, which in turn can lead to better prevention and treatment.

Next, UCLA neuroscientist Tyrone Cannon presented current research from his group and others on prevention of psychosis in at-risk youth. His talk was divided into two parts: (1) recent work in the prediction of psychosis; and (2) understanding the neurobiological mechanisms underlying onset, especially particular aspects of brain development in late adolescence that seem to “go awry.”

The research paradigm for identifying prodromal patients (which is based on “the recent emergence of sub-psychotic intensity or psychotic-like symptomatology”) grew out of what were initially retrospective observations by Patrick McGorry and colleagues of the University of Melbourne (Australia). McGorry’s group identified a period of substantial deterioration prior to onset of full-blown symptoms of psychosocial functioning, combined with the gradual emergence of paranoid ideation, and changes in perception, thinking, and behavior that are characteristic of or on a continuum with what is observed in full-blown illness, albeit not at the same levels of disorganization or intensity. An independent group at Yale led by Thomas McGlashan developed the Structured Interview for Prodromal Syndromes (SIPS) and a severity scale (SOPs). But transition rates in follow-up studies have varied due to the intrinsic limitation of small sample sizes and difficulty in detecting individuals at risk, given the tendency of health care systems to be “reactive” instead of “proactive.”

To increase sample size, eight prodromal psychosis research centers formed a consortium (the North American Prodrome Longitudinal Study; NAPLS) and pooled their data. The new data set has been used to (1) explore the rate of conversion to psychosis and the shape of the survival function over a 30-month follow-up period; and (2) develop a multivariate risk prediction algorithm that can guide the selection of high-risk cases in future studies. Cannon is hopeful that monitoring at-risk individuals will give us a “unique window” into the underlying changes in brain structure and function associated with onset of psychosis.

In the second part of the talk, Cannon focused on neurobiological changes. During adolescence, normal pruning eliminates 40% of cortical synapses. People with schizophrenia show gray matter changes, in particular a greater decrease in dendritic complexity and synaptic density with respect to healthy controls, as well as significant brain surface contraction, primarily in the prefrontal cortex. Potential genetic candidates for gray matter changes include sequence variations in or altered expressions of DISC1, a known susceptibility gene for schizophrenia. Additionally, UCLA prodromal participants failed to show normal age-related increase in medial temporal lobe white matter, which prospectively predicted poorer functional outcome. Cannon concluded that future studies should incorporate neurobiological assays in order to develop a panel of predictive biomarkers for risk of psychotic illness.

The third presentation featured USC law professor Elyn Saks, author of the memoir The Center Cannot Hold: My Journey Through Madness, who discussed her personal experience living with schizophrenia. As a young adult, Saks was given “very poor and grave prognoses”; she was not expected “to live independently, let alone to work” for the rest of her life. Her memoir describes how she fashioned a different life.

By the age of 5, Saks suffered from phobias, obsessions, and night terrors. She also experienced episodes of disorganization: “It was as if my mind was a sand castle with all the sand sliding away in the receding surf and no center to take things in, put them together, and make sense of them.” She experienced her first psychotic episode at 15. Saks graduated first in her class from Vanderbilt University. But her condition worsened while at Oxford University as a Marshall Scholar. She became “officially mentally ill” and was hospitalized twice at Warneford Hospital. On the advice of a sympathetic consulting psychiatrist trained in psychoanalysis (Anthony Storr), Saks resumed her studies in ancient philosophy while under psychoanalysis with a British practitioner and eventually attended Yale Law School. (For Saks, a woman of prodigious intelligence and infectious good humor, work is generally “the last thing to go.”) She was re-hospitalized and diagnosed with “chronic paranoid schizophrenia” in New Haven and, this time, put in restraints, force-fed an antipsychotic, and periodically secluded. Upon release, Saks re-entered psychoanalysis, graduated from Yale, and eventually joined the faulty of University of Southern California. Although she continued to experience psychotic episodes, she was never hospitalized again, which she attributes to medication and psychoanalysis. Saks said that, “Ironically, the more I accepted I had a mental illness, the less the illness defined me.” Talk therapy in particular allowed her to “take the chains” off her mind and fall apart. To her British psychoanalyst, “my thoughts and feelings were not right or wrong, good or bad, they just were.” She also said that psychoanalysis “has been the key to every other relationship I hold precious.”

Based on her experiences in both British and American psychiatric hospitals, Saks called for a change in treatment policy, particularly in such dehumanizing practices as the use of restraints. She also said that psychoanalytic or psychodynamic therapy is underrated, and should be central to treatment. Finally, echoing Kay Jameson, she stressed the importance of social bonds in recovery. Saks emphasized that her success was facilitated by the support and care of her close friends and husband. She is currently working on a joint UCLA-USC study on the lives and success of high-functioning persons with schizophrenia in Los Angeles.

In the session’s final presentation, psychological anthropologist Robert Lemelson screened his ethnographic film, Shadows and Illuminations [see trailer below]. The film, which is the first of a 3-part series entitled Afflictions: Culture and Mental Illness in Indonesia, is based on 12 years of anthropological fieldwork in Indonesia to assess long-term recovery from serious mental illnesses. It focuses on the personal life narrative of a rural Balinese man in his late sixties known as Pak Kereta, who suffers from a psychotic-like illness. In the film, Pak Kereta describes a continuous intrusion of “shadows” or spirits in the form of sounds, apparitions (which he calls “illuminations”), and voices, which have made him fearful and reclusive and disrupted his marriage and working life.

The film covers Pak Kereta’s personal history of trauma (stemming from political violence in 1965 after a purported Communist coup), the loss of a child, and exposure to pesticides, all of which may have contributed to his illness experience. Importantly, the film places his experience in the context of local community and cultural beliefs and practices and the social and political history of the region. Additionally, it draws on family members and local mental health practitioners’ observations and perspectives. In this way, the film explores how Pak Kereta’s experiences can be arranged and interpreted in multiple ways.

In terms of treatment, an Indonesian psychiatrist describes how she diagnosed Pak Kereta with paranoid schizophrenia. In a follow-up visit, she meets with him and adjusts his medication (Thorazine). Pak Kereta also visits two healers, the first of whom douses his head with an elixir and diagnoses a stress-related problem (based on the location of the illness in the center of the chest). The second healer said Pak Kereta was “mute” and living “in fear” at the beginning of treatment 25 years ago, which involved a 3-month stay. In a follow-up visit he identifies Pak Kereta’s illness as “ngeb,” a condition caused by people, i.e., witchcraft, the treatment for which is a traditional mantra or verbal incantation and medicinal drops in the eyes and nose. In a subsequent interview, both Pak Kereta and his wife say they prefer the Western pills, which “work,” as opposed to the drops, which “burn.”

The film concludes with a consideration of how Pak Kereta has adapted to his illness and hallucinations (he and his wife claim the illness has brought them closer). “There are other people who are sick and, until they die, nobody cares for them,” he said. “They just disappear.” Lemelson describes how he came to realize that Pak Kereta’s “experiences with spirits could not be viewed purely as a psychiatric illness.” He said it was “the lack of a label of madness with its attendant social meanings that allowed Kereta to exist and find a small measure of peace in his own world.” In the end, Lemelson said, “Kereta still had to come to his own understandings and ways of co-existing with his ever-present spirits.”

Commentaries

In the first commentary, Caltech neurobiologist Paul Patterson discussed the “seemingly unrelated and very diverse risk factors” associated with schizophrenia, such as maternal infection, maternal malnutrition, obstetric complications, being born in the winter/spring months, and being born and brought up in an urban environment. Common to all these factors is an association with an inflammatory response, he said, in particular an elevated level of a specific cytokine known as interleukin-6.

Patterson cited epidemiological work by Alan Brown and colleagues at Columbia on the significant increase in schizophrenia risk following prenatal influenza exposure. The group’s “calculation of attributable risk” indicates that some 15–20 percent of schizophrenia cases could have been prevented if the infection had not occurred. Attributable risk increases to approximately 30 percent with the inclusion of other, non-overlapping infections that have also been associated with schizophrenia risk, such as other viral, bacterial, and parasitic infections. “And the important thing about that,” Patterson continued, “is that we’re not just thinking about potential causes and risks factors, the important thing is that these are in some sense preventable. There are public health and personal measures one can take to try to prevent maternal infection.”

Patterson then discussed his own recent work on mouse models of maternal infection. A respiratory infection mid-gestation in the mother results in a number of behaviors in the offspring that are consistent with those found in schizophrenia and even autism, such as social interaction deficits and anxiety under mildly stressful conditions, as well as differences in objective measures like pre-pulse inhibition and latent inhibition. The offspring have enlarged ventricles, as seen in schizophrenia, and a loss or deficit in Purkinje cells, one of the most common neuropathologies found in autism.

Patterson and others have also found that many of these behavioral deficits are post-adolescence in onset. Treatment of adolescent animals with antipsychotic drugs prevents the onset of these abnormal behaviors as well as ventricular enlargement. These findings suggest that public health measures (to prevent maternal infection) as well as medical or biological approaches to prevent conversion in at-risk individuals all hold promise.

In his concluding remarks he said that work by Alan Brown’s group suggests schizophrenia can be subdivided according to potential causal factors; persons with schizophrenia who were exposed to influenza prenatally display distinct pathologies and cognitive deficits from schizophrenics whose mothers were not infected.

Mary-Jo DelVecchio Good, a professor of social medicine at Harvard, presented the last commentary of the session. She reflected on how beautifully Elyn Saks conveyed the love she received from her friends and the support she received from mental health practitioners during her terrifying experiences with psychosis. She also noted the many levels through which Pak Kereta’s experiences can be interpreted, particularly the sinister overtones of the spirits when the story is presented in a political context.

She described the amazing complexity (of both stories) in terms of looking through so many layers of narrative. She compared Elyn’s narrative, in which she is controlling the story she is telling us, to the different versions of Pak Kereta’s story, noting that Shadows and Illuminations is a far more personal story than the narrative that appears in 40 Years of Silence, another ethnographic film by Robert Lemelson that focuses on the events of 1965, in which Pak Kereta’s psychosis might be considered a protective mechanism in reaction to the horrors he experienced.

In closing she said one of the questions we need to ask is, how these various narratives (the neuroscientific, the ethnographic, the political, the personal, and so on) are structured. She said that a common thread among them is emotion, noting the affective power of brain images, as well as personal stories. She also asked the audience to consider how the stories we tell relate to ourselves as subjects and to others, like Pak Kereta, as subjects and to remain mindful of the moral consequences of our interpretations.

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.