Postmortem studies on mitochondria in schizophrenia

Schizophr Res. 2017 Sep:187:17-25. doi: 10.1016/j.schres.2017.01.056. Epub 2017 Feb 9.

Abstract

The aim of this paper is to provide a brief review of mitochondrial structure as it relates to function and then present abnormalities in mitochondria in postmortem schizophrenia with a focus on ultrastructure. Function, morphology, fusion, fission, motility, ΔΨmem, ATP production, mitochondrial derived vesicles, and mitochondria-associated ER membranes will be briefly covered. Pathology in mitochondria has long been implicated in schizophrenia, as shown by genetic, proteomic, enzymatic and anatomical abnormalities. The cortex and basal ganglia will be reviewed. In the anterior cingulate cortex, the number of mitochondria per neuronal somata in layers 5/6 in schizophrenia is decreased by 43%. There are also fewer mitochondria in terminals forming axospinous synapses. In the caudate and putamen the number of mitochondria is abnormal in both glial cells and neurons in schizophrenia subjects, the extent of which depends on treatment, response and predominant lifetime symptoms. Treatment-responsive schizophrenia subjects had about a 40% decrease in the number of mitochondria per synapse in the caudate nucleus and putamen, while treatment resistant cases had normal values. A decrease in mitochondrial density in the neuropil distinguishes paranoid from undifferentiated schizophrenia. The appearance, size and density of mitochondria were normal in the nucleus accumbens. In the substantia nigra, COX subunits were affected in rostral regions. Mitochondrial hyperplasia occurs within axon terminals that synapse onto dopamine neurons, but mitochondria in dopamine neuronal somata are similar in size and number. In schizophrenia, mitochondria are differentially affected depending on the brain region, cell type, subcellular location, treatment status, treatment response and symptoms.

Keywords: Cytochrome oxidase; Electron microscopy; Neuropathology; Postmortem; Psychosis.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure*
  • Mitochondrial Diseases / drug therapy
  • Mitochondrial Diseases / metabolism
  • Mitochondrial Diseases / pathology
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*
  • Schizophrenia / pathology*

Substances

  • Antipsychotic Agents