FPR-UCLA 4th Interdisciplinary Conference - Summaries

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Session 4 Summary: Cultural and Biological Contexts of Bipolar Disorder

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.

In the next talk, neuroscientist Mary Phillips, professor of psychiatry at the University of Pittsburgh, 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 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 BD 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.


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