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Metabolic Gating and the Evolution of Human Cognitive Plasticity: A Comparative Genomic Analysis
1Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, 650 W. Baltimore Street, Baltimore, MD 21201, U.S.A.
Biorxiv : the Preprint Server for Biology
|June 29, 2026
Summary
Genetic links between scientific innovation and neuropsychiatric conditions like schizophrenia are revealed. A "Vanguard Engine" of genes supports cognitive plasticity but may cause collapse on a high-carbohydrate diet.
Area of Science:
- Neurogenetics
- Cognitive Neuroscience
- Psychiatric Genetics
Background:
- The genetic underpinnings of exceptional cognitive plasticity in human innovators are not well understood.
- Existing research suggests potential overlaps between genes associated with scientific creativity and those linked to neuropsychiatric disorders.
Purpose of the Study:
- To investigate the genomic architecture of scientific innovation.
- To explore the relationship between genetic factors for innovation and neuropsychiatric phenotypes.
- To identify key genetic networks involved in cognitive plasticity.
Main Methods:
- Comparative genomic analysis using psychiatric cohorts (Psychiatric Genomics Consortium) and UK Biobank (Scientific Creativity).
- Identification of specific genes and genetic variants associated with cognitive traits and neuropsychiatric risks.
- Analysis of metabolic and epigenetic regulators linked to neural plasticity.
Main Results:
- A coordinated genetic network, termed the "Vanguard Engine," was identified, including genes for voltage-gated calcium channels (CACNA1C, CACNB2), glutamatergic receptors (GRIN2A), synaptic plasticity (BDNF), and language (FOXP2).
- This network appears to create a high-voltage neural environment conducive to associative divergence.
- Metabolic loci (PDHB, HCAR2) and epigenetic factors (HDAC2) were linked to the regulation of this plasticity network, influenced by fuel availability (β-hydroxybutyrate).
Conclusions:
- Extreme cognitive innovation and psychiatric pathology may exist on a spectrum driven by a "fuel-mismatch."
- A high-performance cognitive architecture, potentially supported by a carbohydrate-rich diet, may lead to systemic thermodynamic failure.
- This framework offers a unified explanation for the link between cognitive innovation and neuropsychiatric conditions.
Keywords:
Balancing SelectionBeta-hydroxybutyrateCognitive PlasticityEvolutionary PsychiatryHCAR1 (GPR81)HCAR2 (GPR109A)LactateMetabolic PsychiatryPolygenic ArchitectureSchizophreniaMore Related Videos
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