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.