Mitochondrial dysfunction in schizophrenia: With a focus on postmortem studies

Among the many brain abnormalities in schizophrenia are those related to mitochondrial functions such as oxidative stress, energy metabolism and synaptic efficacy. The aim of this paper is to provide a brief review of mitochondrial structure and function and then to present abnormalities in mitochondria in postmortem brain in schizophrenia with a focus on anatomy. Deficits in expression of various mitochondrial genes have been found in multiple schizophrenia cohorts. Decreased activity of complexes I and IV are prominent as well as abnormal levels of individual subunits that comprise the complexes of the electron transport chain. Ultrastructural studies have shown layer, input and cell specific decreases in mitochondria. In cortex, there are fewer mitochondria in axon terminals, neuronal somata of pyramidal neurons and oligodendrocytes in both grey and white matter. In the caudate and putamen mitochondrial number is linked with symptoms and symptom severity. While there is a decrease in the number of mitochondria in astrocytes, mitochondria are smaller in oligodendrocytes. In the nucleus accumbens and substantia nigra, mitochondria are similar in density, size and structural integrity in schizophrenia compared to controls. Mitochondrial production of ATP and calcium buffering are essential in maintaining synaptic strength and abnormalities in these processes could lead to decreased metabolism and defective synaptic activity. Abnormalities in mitochondria in oligodendrocytes might contribute to myelin pathology and underlie dysconnectivity in the brain. In schizophrenia, mitochondria are affected differentially depending on the brain region, cell type in which they reside, subcellular location, treatment status, treatment response and predominant symptoms.