Title : Sensoria driven genetic decoupling and impaired areal integration in diseases of agency
Abstract:
Whole genome studies of diseases of agency, like schizophrenia, have thus far failed to identify gene candidates exerting more than a marginal influence on behavioral symptoms. Affected single nuclear polymorphisms (SNPs) number well above 12,000 indicating likely pool sizes of risk alleles running potentially into the thousands. The indiscriminate and massive number of affected alleles seen in these studies implicates a higher order, organizational and regulatory impairment, rather than one involving specific genetic factors, which affects self- recognition and the ability to execute actions. Such a substrate is likely to be embedded within the interactive properties of large cell clusters such as those comprising neural circuits or even large-scale networks of the brain, which adopt top down regulatory control over behavioral and motor actions. This process of decoupling regulation from genetic oversight to one entailing a systemic and top down supracellular organization raises questions regarding whether the decoupling process itself or the systemic organization are impaired in these diseases. A failure in epigenetic mechanisms, for example, could affect the development of top down neural control, given that decoupling processes involve developmental events. Experience dependent, gene ontology experiments, however, are consistent with a primary defect in the neural regulatory structure itself. Consistent with this latter possibility, impaired body representations are correlated with the inability to attribute actions to oneself. Such representations are built from sensorial input during development, which appears to drive genetic decoupling and the generation of top down control. Several leading proposals link the sensorial representation of the body to the self/agent - and could offer a model for investigating the etiology of the disease. The inability to attribute actions to the self indicates a lack of self recognition, which is likely to represent a failure in sensorial input from the body to drive the formation of a global regulatory structure, points which will be discussed in this talk.
