Insights into the genomics of affective disorders

Abstract

Abstract Affective disorders, or mood disorders, are a group of neuropsychiatric illnesses that are characterized by a disturbance of mood or affect. Most genetic research in this field to date has focused on bipolar disorder and major depression. Symptoms of major depression include a depressed mood, reduced energy, and a loss of interest and enjoyment. Bipolar disorder is characterized by the occurrence of (hypo)manic episodes, which generally alternate with periods of depression. Formal and molecular genetic studies have demonstrated that affective disorders are multifactorial diseases, in which both genetic and environmental factors contribute to disease development. Twin and family studies have generated heritability estimates of 58–85 % for bipolar disorder and 40 % for major depression. Large genome-wide association studies have provided important insights into the genetics of affective disorders via the identification of a number of common genetic risk factors. Based on these studies, the estimated overall contribution of common variants to the phenotypic variability (single-nucleotide polymorphism [SNP]-based heritability) is 17–23 % for bipolar disorder and 9 % for major depression. Bioinformatic analyses suggest that the associated loci and implicated genes converge into specific pathways, including calcium signaling. Research suggests that rare copy number variants make a lower contribution to the development of affective disorders than to other psychiatric diseases, such as schizophrenia or the autism spectrum disorders, which would be compatible with their less pronounced negative impact on reproduction. However, the identification of rare sequence variants remains in its infancy, as available next-generation sequencing studies have been conducted in limited samples. Future research strategies will include the enlargement of genomic data sets via innovative recruitment strategies; functional analyses of known associated loci; and the development of new, etiologically based disease models. Researchers hope that deeper insights into the biological causes of affective disorders will eventually lead to improved diagnostics and disease prediction, as well as to the development of new preventative, diagnostic, and therapeutic strategies. Pharmacogenetics and the application of polygenic risk scores represent promising initial approaches to the future translation of genomic findings into psychiatric clinical practice.