Mitochondrial Dysfunction in Neuropsychiatric Disorders

Mitochondrial disorders were first described in 1962 (Luft, Ikkos, Palmieri, Ernster, & Afzelius, 1962), and were initially thought to be uniformly progressive and fatal with onset in infancy or early childhood, typically associated with severe neurological manifestations, including strokelike episodes, seizures, neuronal degeneration, organ failure and dementia. More recently, clinical observation and research has increasingly discovered a tremendous variety of more mild cases of adult-onset mitochondrial disorders and mitochondrial dysfunction in many diseases not previously thought of as “mitochondrial” in nature, suggesting that mitochondrial dysfunction not only manifests a diverse array of phenotypes, but may be a final common pathway in many disease states, as well as normal ageing. For a variety of reasons, the brain and nervous system are uniquely vulnerable to mitochondrial dysfunction, and many neurobehavioral symptoms may be related to impaired mitochondrial activity. This paper will discuss the origin and function of mitochondria, the pathogenesis of mitochondrial disease, and the neurobehavioral effects of mitochondrial dysfunction.