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Mitochondrial Dysfunction and Psychiatric Disorders

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Abstract

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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Abbreviations

5-HT1A:

5-Hydroxytryptamine 1A

5-HT1B:

5-Hydroxytryptamine 1B

ACC:

Anterior cingulate cortex

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

cAMP:

Adenosine monophosphate cyclic

CREB:

cAMP response element-binding

HPA:

Hypothalamic-pituitary-adrenal

mtDNA:

Mitochondrial deoxyribonucleic acid

mRNA:

Messenger ribonucleic acid

MRS:

Magnetic resonance spectroscopy

PCR:

Polymerase chain reaction

PET:

Positron emission tomography

rCBF:

Regional cerebral blood flow

ROS:

Reactive oxygen species

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Acknowledgments

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.

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Authors and Affiliations

  1. Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciuma, SC, Brazil

    Gislaine T. Rezin & Emilio L. Streck

  2. Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciuma, SC, Brazil

    Graziela Amboni, Alexandra I. Zugno & João Quevedo

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  1. Gislaine T. Rezin
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  2. Graziela Amboni
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Correspondence to Emilio L. Streck.

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Rezin, G.T., Amboni, G., Zugno, A.I. et al. Mitochondrial Dysfunction and Psychiatric Disorders. Neurochem Res 34, 1021–1029 (2009). https://doi.org/10.1007/s11064-008-9865-8

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