Presentation and Management of Acute Mania in Fanconi–Bickel Syndrome, A Metabolic Genetic Disorder

Figure 1

A loss of GLUT2 induces and overactivation of the PVT-to-nucleus accumbens and PVT-to-amygdala circuit, contributing to acute mania and impulsivity in FBS. As demonstrated by Labouebe et al. [17], the PVT harbors a GLUT2+ glutamatergic population. Critically, they demonstrated that GLUT2 inactivation or local hypoglycemia induces activation of the PVT. On top is a cartoon depiction of the PVT, which has been found to regulate reward seeking and fear memory. The PVT neurons facilitate these behaviors by innervating regions involved in such as the nucleus accumbens and amygdala. On the bottom, we depict what may occur in FBS, with the chronic loss of GLUT2 inducing an overactive PVT network. Thus, we propose that FBS patients may exhibit a chronically overactive PVT and thus dysregulate regions involved in motivational salience and emotional processing such as the amygdala and nucleus accumbens. An overactive amygdala/nucleus accumbens circuit may thus contribute to manic episodes.