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.”
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.