Twin Study Shows Factors Associated With Schizophrenia and Bipolar Disorder

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Identification of biomarkers, genetic and epigenetic variation and the development of specific and common endophenotypes are potential gains from this cohort.
Identification of biomarkers, genetic and epigenetic variation and the development of specific and common endophenotypes are potential gains from this cohort.

A unique cohort consisting of monozygotic and dizygotic same-sex twins diagnosed with schizophrenia or bipolar disorder was characterized for psychiatric symptoms, cognitive function, genetic variation, and relevant biomarkers to support ongoing and planned analyses of these conditions, according to a study published in Schizophrenia Research.

The authors of this large, nationwide cohort study sought to investigate genetic and environmental factors contributing to schizophrenia and bipolar disorders, including the inheritance of neural dysfunctions, by examining same-sex twins who have these conditions. They further sought to identify genetic variations responsible for abnormalities, isolate nongenetic influences, and estimate the extent of overlap between the 2 conditions.

The study cohort recruited 462 same-sex monozygotic and dizygotic twins, born between 1940 and 1986, identified through the Swedish Twin Register. At least 1 twin in each pair met the diagnostic criteria for schizophrenia or bipolar disorder. Five healthy control pairs randomly selected from the Swedish Twin Register were matched to each affected pair by sex and birth year. Participants completed questionnaires about physical health, demographics, smoking habits, personality traits, stressful life events, coping, and social support. Researchers further characterized them using brain imaging, neuropsychological assessments, biomarkers from various lab analyses, and genetic testing.

Of the twins who completed the diagnostic assessment, 16.4% were diagnosed with schizophrenia, 18% with bipolar disorder, 19.8% with major depression, and 45.7% were not affected. In 17% of cases, the presumptive diagnosis reported in the lifetime register changed status during the clinical interview. Cigarette smoking was reported by 15.7% of the overall cohort. In twins with schizophrenia, 25.4% reported smoking daily, whereas 20.3% of twins with bipolar disorder and 19.7% of twins with depression reported smoking. The majority of twins did not live together as adults, but 65.5% kept in frequent touch with their twin partner.

Studies based on the data collected for this cohort — including genetic and epigenetic variation, psychiatric symptoms, cognitive ability, and brain function — have revealed a number of novel associations. For example, co-twins with bipolar disorder scored higher on positive temperaments and cognitive performance whereas enhanced sociability and verbal fluency were associated with liability for bipolar disorder. Impulsivity was a shared expression of endophenotypes found in schizophrenia, bipolar disorder, and depression. Schizophrenia was linked to memory-related genes; structural anomalies found the in the brain along with certain microglia-related markers were associated with liability for both schizophrenia and bipolar disorder.

A limitation of the study was the low response rate of 38.2% during initial recruitment, which was even lower for twins with presumed schizophrenia or bipolar disorder.

The authors indicate that by establishing a unique cohort of monozygotic and dizygotic twins with schizophrenia or bipolar disorder, they have provided the opportunity for future research to identify biomarkers and discover new leads for preventing schizophrenia and bipolar disorder.

This study was sponsored by the National Institute of Health and ALF, a regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Instituet.

Reference                                                                                                                       

Johansson V, Hultman CM, Kizling I, et al. The schizophrenia and bipolar twin study in Sweden (STAR) [published online August 15, 2018]. Schizophr Res. doi: 10.1016/j.schres.2018.08.001

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