Major psychiatric illnesses are profound disorders of thought and emotion, which are strongly associated with underlying impairments in synaptic plasticity and cellular resilience. Evidence from functional assays, protein expression studies, and linkage analyses, points to a specific role for mitochondria in psychiatric disorders. Individuals with bipolar disorder also have been shown to have impaired brain energy metabolism and increased mitochondrial DNA mutations.
Hermes and colleagues use a genetic model in which mitochondrial responses to energy demands are impaired. The mouse model presented here includes a deletion of uncoupling protein 2 (UCP2), a mitochondrial membrane protein that separates oxidative phosphorylation from ATP synthesis via controlled proton re-entry into the mitochondrial matrix. The authors show that in the absence of UCP2, neurons are less plastic in response to stress. Mitochondrial dysregulation, which may be the result of altered systemic metabolism, may be an important contributor in the etiology of psychiatric disease.