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The molecular self: genetics and neurochemistry of self-consciousness

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The empirical study of self-consciousness has ontological and clinical relevance. The current Research Topic aims to elucidate which molecular mechanisms shape neural circuits related to self-consciousness and confer risk for disease.

Self-consciousness is a construct comprising ...

The empirical study of self-consciousness has ontological and clinical relevance. The current Research Topic aims to elucidate which molecular mechanisms shape neural circuits related to self-consciousness and confer risk for disease.

Self-consciousness is a construct comprising component processes such as bodily self-consciousness, self-agency, self-affectivity, and semantic self-knowledge. The wide spectrum of associated neurological and psychiatric disorder indicates that, although interconnected to create a unified sense of self, these are dissociated processes, thus highlighting the complexity of molecular mechanisms involved in self-consciousness.

In genetic terms, the heterogeneity of self-consciousness sub-processes best classifies it as a complex trait. The investigation of the genetic underpinning of other complex traits related to neuropsychiatric diseases demonstrates a wealth of partially overlapping polygenic influences. Pertinent genome-wide screening technologies (GWAS, whole exome sequencing, WES) are unravelling the genetic and non-genetic sources of variation, as well as their interplay influencing genetic architectures. Discoveries comprise common variants of small effect sizes, as well as rare and de novo variants of intermediate and large effects. They are likely to interact with the individual’s genetic background (gene-by-gene interaction, epistasis), as well as environmental factors and resulting epigenetic programming that ultimately involves multi-layered regulatory mechanisms operating at the neural network level. Causative polygenic pathomechanisms of disease coexist with pleiotropic consequences of a single genetic variation influencing multiple phenotypic expression patterns. To date, scarce evidence supports the role of polygenic mechanisms in self-consciousness, but details of candidate genes, influencing factors as well as potential overlap remains to be fully elucidated for most of its constituent processes.

The role of neurotransmitters in emergence and modulation of self-consciousness is robustly supported by early studies on drug-induced altered states of consciousness. Individual variations in response to hallucinogen intake, expressed in the concept of “set and setting”, hint for the existence of an equally complex array of candidate transmitters correlates of self-consciousness and their deficits underlying disorders of the self, as those suggested in genetic research. How to approach the interaction between principal transmitters, such as glutamate and GABA, which balance the general level of brain activity, with modulatory transmitters, e.g. dopamine and serotonin, whose widespread connections to many brain areas confers them with an extending integrative potential, a mechanism of “volume control”? Shall the research be restricted to identification of endogenous transmitters and their receptor pathways, or shall intracellular processes also be targeted such as ligand-dependent signalling cascades in accordance to the functional selectivity hypothesis of neuromodulation already investigated in animal model psychosis research? And most importantly, which are the links between self-related circuit function and genetic variants, which are related to neurotransmitter signalling?

The current Research Topic represents an unique opportunity to call attention to this widely neglected molecular approach to self-consciousness, gathering new evidence for novel concepts, and opening debate for future directions of research in the field. We welcome articles from all domains of neuroscience research, including e.g. neurology, psychiatry and philosophy. All types of articles are accepted, original research, methods, hypothesis, theory and opinions.


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