Etiopathogenesis of bipolar affective disorder - the state of the art for 2021.

The contemporary clinical idea of bipolar affective disorder (BD) has been shaped as an aftermath of Emil Kraepelin's thought named "manisch-depressives Irresein", put forward in 1899, with essential modifications during the last half-century. Acurrent paradigm for the etiopathogenesis of BD postulates the emergence of the illness as a result of an interaction between genetic and epigenetic factors with environmental influences.The most important for the molecular genetics of BD were the analyses of so-called candidate genes and genome-wide association studies (GWAS). The genetic BD profile includes many genes predisposing to other psychiatric disorders. Epigenetic disturbances constitute a mediating mechanism for the influence of environmental factors in the early period of life. Some neurobiological concepts of BD have a pharmacological origin, resulting from the mechanisms of the drugs used in the illness. They include catecholamine, cation transport, and purinergic theories. Such concepts as the neuroplasticity disturbances, "inflammatory" theory, and stress axis dysfunction resulted as an extrapolation of the initial pathogenetic hypotheses of depression. New pathogenetic theories of BD include the disturbances of biological rhythms and mitochondrial and oxidative stress dysfunctions. In BD there are abnormalities of the functions of the brain structures, in particular, the so-called anterior limbic system. Pathogenetic environmental influences include factors operating in pregnancy, early childhood trauma, stressful events in later life as well as seasonal and climatic factors. Both the pathogenesis and the course of BD are presently perceived in a developmental context, reflected by the staging concepts of the illness.