Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia.

The haploinsufficiency of genes within the 22q11.2 region leads to multifaceted mitochondrial dysfunction with consequences to neuronal function, viability, and wiring. Overlap between in vitro and in vivo studies implies a causal role between impaired mitochondrial function and the development of schizophrenia in 22q11.2DS.22q11.2 deletion syndrome leads to changes in energy metabolism: Lower ATP levels, enhanced glycolysis and decreased OXPHOS rates, decreased antioxidant capacity, and aberrant calcium homeostasis. Although 22q11.2DS is the strongest single genetic risk factor for schizophrenia development, prenatal or postnatal insults (as indicated by the second hit) are necessary for schizophrenia to develop.