Neurobiology

Risk Genes

ST3GAL3

Golgi enzyme: beta-galactoside-alpha-2,3,-sialyltransferase-III
Terminal sialylation of glycoproteins involved in myelination and some gangliosides
Risk gene for intellectual disability

Decreased oligodendrocyte progenitor cells & hypomyelination in ST3GAL3-deficient mice
ST3GAL3 initiates polysiaylation of NCAM1

NCAM1

Promotes cell-cell & cell-extracellular matrix (ECM) adhesion via homophilic and heterophilic interactions
Expressed in both neurons and glia
Involved in:
- Brain development (cell proliferation/migration, neurite outgrowth, pathfinding, synaptogenesis)
- Adult brain (synaptic plasticity, learning & memory)

MEF2C

Myocyte enhancer factor 2C
Risk gene for intellectual disability, featuring deficits in white matter integrity and myelination
Negatively regulates dendritic spines

LPHN3

Paisa: Genetic isolate of Europeans in Antioquia, Columbia
Linkage study ADHD risk haplotype of LPHN3
Mediates synapse specificity
Discovery of its function
- Latrodectism by the black widow causes massive release of neurotransmitters
  - OG treatment is a dance called tarantella which starts slowly and then accelerates to sweat out the venom
- Morpholino injection in zebrafish can knock out LPHN3 and then study embryos, locomotor behavior, and neuroanatomy

Neuropeptide Y

Frontostriatal dysfunction

Hippocampus, SN, VTA, amygdala, NAc, dSTR, and PFC interactions are disrupted in ADHD

Interneuron-myelination interplay and excitation/inhibition (E/I) balance

Maternal stress
Alcohol, smoking, drug consumption during pregnancy (meth…)
Environmental toxins (organophosphates, polychlorinated biphenyls (PCBs), lead)
Preterm birth, low birth weight
Unfavorable psychosocial conditions (severe early-childhood deprivation, maternal hostility, physical abuse)