Mitochondrial oxidative phosphorylation is the major ATP-producing pathway, which supplies more than 95% of the total energy requirement in the cells. Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders. Tissues with high energy demands, such as the brain, contain a large number of mitochondria, being therefore more susceptible to reduction of the aerobic metabolism. Mitochondrial dysfunction results from alterations in biochemical cascade and the damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neuropsychiatric disorders, such as bipolar disorder, depression and schizophrenia. Bipolar disorder is a prevalent psychiatric disorder characterized by alternating episodes of mania and depression. Recent studies have demonstrated that important enzymes involved in brain energy are altered in bipolar disorder patients and after amphetamine administration, an animal model of mania. Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Several works have demonstrated that metabolism is impaired in some animal models of depression, induced by chronic stress, especially the activities of the complexes of mitochondrial respiratory chain. Schizophrenia is a devastating mental disorder characterized by disturbed thoughts and perception, alongside cognitive and emotional decline associated with a severe reduction in occupational and social functioning, and in coping abilities. Alterations of mitochondrial oxidative phosphorylation in schizophrenia have been reported in several brain regions and also in platelets. Abnormal mitochondrial morphology, size and density have all been reported in the brains of schizophrenic individuals. Considering that several studies link energy impairment to neuronal death, neurodegeneration and disease, this review article discusses energy impairment as a mechanism underlying the pathophysiology of some psychiatric disorders, like bipolar disorder, depression and schizophrenia.
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The authors would like to thank UNESC (Brazil), FAPESC (Brazil) and CNPq (Brazil) that supported the studies of our group that are cited in this review.
Calabrese V, Scapagnini G, Giuffrida-Stella AM et al (2001) Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res 26:739–764. doi:10.1023/A:1010955807739PubMedCrossRefGoogle Scholar
Horn D, Barrientos A (2008) Mitochondrial copper metabolism and delivery to cytochrome c oxidase. IUBMB life. doi:10.1002/iub.50
Sun X, Wang JF, Tseng M et al (2006) Downregulation in components of the mitochondrial electron transport chain in the postmortem frontal cortex of subjects with bipolar disorder. J Psychiatry Neurosci 31:189–196PubMedGoogle Scholar
Schnyder T, Gross H, Winkler H et al (1991) Crystallization of mitochondrial creatine kinase. Growing of large protein crystals and electron microscopic investigation of microcrystals consisting of octamers. J Biol Chem 266:5318–5322PubMedGoogle Scholar
Wallimann T, Wyss M, Brdiczka D et al (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281:21–40PubMedGoogle Scholar
Artigas F (2008) Serotonin receptors: role in depression. Actas Esp Psiquiatr 36:28–30Google Scholar
Ruhé HG, Mason NS, Schene AH (2007) Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 12:331–359. doi:10.1038/sj.mp.4001949PubMedCrossRefGoogle Scholar
Rezin GT, Cardoso MR, Gonçalves CL et al (2008) Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int. doi:10.1016/j.neuint.2008.09.012
Konarski JZ, McIntyre RS, Kennedy SH et al (2008) Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder. Bipolar Disord 10:1–37PubMedGoogle Scholar
Lee BT, Seok JH, Lee BC et al (2008) Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32:778–785. doi:10.1016/j.pnpbp.2007.12.009PubMedCrossRefGoogle Scholar
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders DSM-IV-TR (4th edn, text revision). American Psychiatric Association, WashingtonCrossRefGoogle Scholar
McGlashan TH, Fenton WS (1992) The positive/negative distinction in schizophrenia: review of natural history validators. Arch Gen Psychiatry 49:63–72PubMedGoogle Scholar
Dror N, Karry R, Mazor M et al (2002) State dependent alterations in mitochondrial complex I activity in platelets: A potential peripheral marker for schizophrenia. Mol Psychiatry 7:995–1001. doi:10.1038/sj.mp.4001116PubMedCrossRefGoogle Scholar
Tamminga CA, Thaker GK, Buchanan R et al (1992) Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry 49:522–530PubMedGoogle Scholar
Hazlett EA, Buchsbaum MS, Byne W et al (1999) Three-dimensional analysis with MRI and PET of the size, shape, and function of the thalamus in the schizophrenia spectrum. Am J Psychiatry 156:1190–1199PubMedGoogle Scholar
Chua SE, McKenna PJ (1995) Schizophrenia: A brain disease? A critical review of structural and functional cerebral abnormality in the disorder. Br J Psychiatry 166:563–582PubMedCrossRefGoogle Scholar
Uranova NA, Aganova EA (1989) Ultrastructure of synapses of the anterior limbic cortex in schizophrenia. Zh Nevropatol Psikhiatr Im S S Korsakova 89:56–59PubMedGoogle Scholar
Kung L, Roberts RC (1999) Mitochondrial pathology in human schizophrenic striatum: a post-mortem ultrastructural study. Synapse 31:67–75. doi:10.1002/(SICI)1098-2396(199901)31:1<67::AID-SYN9>3.0.CO;2-#PubMedCrossRefGoogle Scholar