Is a "Mitochondrial Psychiatry" in the Future? A Review

The field of "mitochondrial medicine" has advanced rapidly since the first patient with a mitochondrial disorder, a concept primarily used for defects of the respiratory chain, was described in 1962 and the first mitochondrial DNA (mtDNA) mutations were described in 1988. Because of the ubiquitous requirement for energy and unique aspects of mtDNA genetics, mtDNA mutations are known to cause a bewildering spectrum of clinical manifestations. However, because of its high-energy requirement, brain is the primary tissue affected in mitochondrial disorders. Using a variety of approaches, mitochondrial function has been shown in numerous studies to be abnormal in patients with schizophrenia and depression. Although less studied, an increase of psychiatric symptoms and disorders, in particular depression, are likely present in patients with mitochondrial disorders. The major categories of drugs used to treat schizophrenia and depression have been demonstrated to exert effects on mitochondria. The authors conclude that an association between energy metabolism and the mental disorders of schizophrenia and depression has been well documented, but that no conclusive evidence as yet demonstrates a causal relationship. A "mitochondrial psychiatry" model is proposed in which a moderate reduction in mitochondrial energy metabolism, genetically determined and/or acquired, is one predisposing factor in the multi-factorial development of certain chronic mental disorders. Clinical implications of our hypothesis, present and future, include the presence of co-morbid somatic symptoms/conditions, and specific treatment at least in highly-selected cases.