Fibromyalgia & Bipolar Spectrum Disorder: A Shared Pathophysiology May Lead to Better Drug Targets

Fibromyalgia is a chronic, disabling condition associated with psychological distress, sleep disturbances and fatigue. Interestingly, many of these symptoms overlap with those of bipolar spectrum disorder. Moreover, accumulating evidence suggests that a shared pathophysiological process may underlie the overlap in symptoms. Beatrice Bortolato, MD, director of psychiatric medicine at Veneto Orientale in Italy, and colleagues published their review of the evidence of the association between fibromyalgia and bipolar spectrum disorder in the February 2016 issue of Current Molecular Medicine.¹ In their review, the authors suggest that a better understanding of the potential biological underpinning shared by fibromyalgia and bipolar disorder may lead to the identification of novel drug targets.

One such thought-provoking example is the observation that individuals with fibromyalgia, as well as individuals with bipolar spectrum disorder, appear to have an overactivation of the kynurenine pathway that drives tryptophan away from the production of serotonin and melatonin. This overactivation can lead to affective symptoms, circadian rhythm disturbances and abnormalities in processing pain. Several studies have also provided evidence of a disturbed stress response in individuals with fibromyalgia and bipolar spectrum disorder. This second observation led the authors to suggest that a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis may be important for the pathophysiology of both fibromyalgia and bipolar spectrum disorder.

Although some research has been performed in the area of melatonin, immune dysfunction and genetic substrates, the bulk of the research implicating a shared pathophysiological pathway between fibromyalgia and bipolar spectrum disorder comes from brain imaging studies. In addition to identifying overlapping structural manifestations, the results suggest that both disorders are associated with impaired neuroplasticity.

Structure
Typically, fibromyalgia is considered the result of aberrant pain transmission, in general, and a dysregulation of descending regulatory pain pathways, in particular. This conclusion is supported by magnetic resonance imaging (MRI) studies of individuals with fibromyalgia that revealed a decrease in gray matter density in areas of the brain involved with pain transmission and processing. Functional MRI has also demonstrated that individuals with fibromyalgia have greater activation of the pain matrix areas of the brain when compared with healthy controls. Finally, magnetic resonance spectroscopy has revealed that individuals with fibromyalgia have alterations in the activity of the insula, the cingulate cortex, the amygdala and the nucleus accumbens.

Although imaging studies of fibromyalgia patients appear to form a clear pattern, generalizing the images of individuals with bipolar disorder syndrome can be more challenging because the patient population is heterogeneous with regard to duration of illness and treatment status. Nevertheless, imaging studies of individuals with bipolar spectrum disorder suggest some structural and functional abnormalities in the prefrontal cortices (PFC). Additionally, patients have significantly decreased volume in the subgenual anterior cingulate cortex (ACC) and increased volume in the amygdala. The increased amygdala volume is associated with heightened activity, particularly during mania. Studies that use diffusion tensor imaging revealed that patients with bipolar disorder also have altered connectivity between the subgenual ACC and the amygdala, the frontal and occipital cortices, the insula and the thalamus.