The endophenotype project and the validation theory: integration of neurobiology and psychiatry

In this paper we set forth the major meta-empirical concepts for mental disorders determination. We especially focus on the methodological prerequisites and particular compounds and the endophenotype construct in a case study of bipolar disorders. It is discussed as a mediating level between the genetic causation and the environmental influences in the mental disorder causation. This epigenetic area includes such constructs as cognitive neuropsychological markers, neurotrophic proteins impairment, instability of circadian rhythms (other chronobiological disturbances as well), deregulation of the motivation and reward mechanisms, changes in the GABA metabolism, symptom provocation with "psychotomymetic" agents, etc. Eventually the core ideas of the original validation theory in comparison with the endophenotype concept are shown as milestones of the novel integration of neurobiology and psychiatry. The major issue posed in the endophenotype debate concerns "the independence from the state". According to the formulation of Hassler and Drevets this notion indicates the presentation of the endophenotype regardless of the activity of the disorder, i.e., its presence even in the pre-morbid and remission periods. In the present study we argue that there is another dimension of "state independence" to be assessed. The validation theory in particular defines the entire space-and-time sequence disposition of the endophenotype indicators, e.g. cognitive-psychological and neuroimaging. It is well known that mental states, whether normal or pathological, are very dynamical, just as their neurophysiological correlates are. By this reason it is necessary to explore their relationships simultaneously.