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New Evidence for the Involvement of Mitochondrial Inheritance in Schizophrenia: Results From a Cross-Sectional Study Evaluating the Risk of Illness in Relatives of Schizophrenia Patients

J Clin Psychiatry 2012;73(5):684-690
10.4088/JCP.10m06718

Objective: One of the hypotheses about the genetic factors that contribute to schizophrenia involves mitochondrial DNA (mtDNA), an approximately 16,569-base pair molecule inherited only from the mother. If this hypothesis were true, one would expect a higher frequency of schizophrenia among matrilineal relatives who share mtDNA with a schizophrenia patient than among relatives who do not. This article reports the risk of presenting with schizophrenia, other psychiatric disorders, and conditions related to mitochondrial disorders in relatives who share mtDNA with a schizophrenia patient versus those who do not.

Method: We interviewed 100 schizophrenia patients (DSM-IV criteria) and 147 of their first-degree relatives from November 2007 to November 2009 to collect clinical data from patients and from both sides of each patient’s pedigree. The study was conducted at of a psychiatric teaching hospital in Reus, Spain. Contingency tables were established, and odds ratios were calculated to estimate relative risk.

Results: Relatives who shared mtDNA with a schizophrenia patient had a higher risk of presenting with schizophrenia than those who did not share mtDNA (odds ratio [OR] = 3.05; 95% CI, 1.65–5.72; P < .001). Female but not male relatives who shared mtDNA with a schizophrenia patient also had a higher risk of unipolar depression (OR =10.19; 95% CI, 4.07–32.80; P < .001), panic attack (OR = 15.52; 95% CI, 2.41–643.6; P < .001), and other anxiety disorders (OR = 4.14; 95% CI, 1.84–9.71; P < .001). Some conditions frequently associated with mitochondrial disorders were also more frequent among female relatives who shared mtDNA with a schizophrenia patient than among those who did not.

Conclusions: The results of this study support the hypothesis that mtDNA may be involved in schizophrenia. In females, mtDNA could also be involved in the development of other psychiatric and nonpsychiatric conditions. Further studies are needed to confirm the role of mtDNA in psychiatric disorders.

J Clin Psychiatry 2012; 73(5): 648-690