Neurochemical Research

, 34:1021

Mitochondrial Dysfunction and Psychiatric Disorders

  • Gislaine T. Rezin
  • Graziela Amboni
  • Alexandra I. Zugno
  • João Quevedo
  • Emilio L. Streck
Overview

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.

Keywords

Mitochondria Metabolism Brain Bipolar disorder Depression Schizophrenia 

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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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gislaine T. Rezin
    • 1
  • Graziela Amboni
    • 2
  • Alexandra I. Zugno
    • 2
  • João Quevedo
    • 2
  • Emilio L. Streck
    • 1
  1. 1.Laboratório de Fisiopatologia Experimental, Programa de Pós-graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciumaBrazil
  2. 2.Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciumaBrazil

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