From circadian genes to psychiatric semiology

Psychiatric disorders, such as bipolar disorder and autism spectrum disorders, are highly inherited. Many studies have reported a higher relative risk of developing these disorders than in general population when there is already an affected individual in the family. The heritability of these disorders varies from 70% to 90%. However, the identification of susceptibility genes to these disorders remains difficult, due to their high clinical and etiological heterogeneity. The combination of endophenotypes and environmental factors in genetic studies shed new lights on the biological pathways that are affected in subjects with psychiatric disorders. In particular, sleep disorders and circadian rhythm abnormalities have been frequently reported in these two disorders. Here, we summarize several associations between sleep disorders or circadian rhythm abnormalities and single nucleotide polymorphisms in circadian genes and in genes encoding enzymes of the melatonin synthesis pathway. In particular, we describe studies reporting that polymorphisms in the circadian genes TIMELESS and RORA may increase the risk of developing bipolar disorder by altering circadian rhythms. In addition, we describe studies showing that genetic variations in acetylserotonin methyltransferase (ASMT) identified in patients with psychiatric disorders affect its enzymatic activity. This approach may have therapeutic benefits in bipolar disorders, through the assessment of sleep and circadian rhythms, and a personal management of these alterations. (C) 2021 Elsevier Masson SAS. All rights reserved.