Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study

Abstract

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

Risk and coaggregation of major psychiatric disorders among first-degree relatives of patients with bipolar disorder: a nationwide population-based study

“…The diagnostic codes used were based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The NHIRD has been used extensively in many epidemiologic studies in Taiwan (Chen et al ., 2013; Chen et al ., 2016; Chen et al ., 2018; Cheng et al ., 2018). Taipei Veterans General Hospital institutional review board approved this study.…”

Increased risk of type 2 diabetes among the siblings of patients with schizophrenia

“…The NHIRD has been used extensively in many epidemiologic studies in Taiwan. [31][32][33][34] Inclusion criteria for the unaffected siblings of schizophrenia probands and the control group Individuals who were born before 1990 and had no diagnosis of schizophrenia (ICD-9-CM code: 295) at any time but had siblings with schizophrenia were enrolled as the schizophrenia sibling cohort. The age-, sex-, and birth time-matched (1:4) control cohort was randomly identified after eliminating the study cases, those who had been given a diagnosis of major psychiatric disorders at any time, and those with any sibling with major psychiatric disorders.…”

Increased responses of the reward circuitry to positive task feedback following acute stress in healthy controls but not in siblings of schizophrenia patients

“…patients would complicate the interpretation of data from such investigations. Therefore, in this study we investigated the effects of stress on reward processing in unaffected siblings of schizophrenia patients who do not take any antipsychotics but who are at risk for multiple psychiatric disorders including schizophrenia, bipolar disorder and major depressive disorder (Cheng et al, 2017). Siblings and offspring of schizophrenia patients share on average 50% of the genetic material with the affected patient and exhibit increased baseline dopamine synthesis capacity and transmission (Huttunen et al, 2008;Brunelin et al, 2010) and altered ventral striatum and OFC responses during reward processing in the absence of stress (de Leeuw, Kahn and Vink, 2014;Vink et al, 2015).…”