Fig. 2. Network of a wide variety of factors involved in the etiopathogenesis of bipolar affective disorder (BD).

Main factors described are differences in genetics (especially risk variants), epigenetics (DNA and histone modifications, non-coding RNAs), metabolic alterations; aberrant calcium signaling; alterations in circadian rhythms; oxidative stress, characteristic low-grade chronic inflammation, HPA axis hyperactivation, related to psychological stress and different psychosocial factors, accompanied with multiple changes in different neural circuitries, aberrant neurotransmission and altered neuropeptides. Peripheral blood concentrations of neurotransmitters are altered in BD, where in each phase there seems to be a different pattern of activity for every neurotransmissor. These differences are relevant with respect to healthy controls. Many of these events, together with additional mechanisms like altered biological clocks, mitochondrial dysfunction or telomere shortening can be considered as signs of premature aging. Beyond, all these factors influences and are directly influence by the dysregulation of the MGB axis which acts as a central element of psychiatric disorders. HPA hypothalamic–pituitary–adrenal, GABA gamma-aminobutyric acid.