Genetic risk for schizophrenia: convergence on synaptic pathways Involved in plasticity

摘要: Recent large-scale genomic studies have revealed two broad classes of risk alleles for schizophrenia: a polygenic component mediated through multiple common variants and rarer more highly penetrant submicroscopic chromosomal deletions duplications, known as copy number variants. The focus this review is on the emerging findings from latter subsequent exome sequencing data smaller, deleterious single nucleotide indels. In these studies, schizophrenia patients were found to enriched de novo mutations in genes belonging postsynaptic density at glutamatergic synapses, particularly components N-methyl-D-aspartate receptor signaling complex, including PSD-95 activity-regulated cytoskeleton-associated protein interactors, fragile X mental retardation voltage-gated calcium channels, implicated actin cytoskeletal dynamics. convergence onto coherent biological pathway synapse, with specific role plasticity, provides significant advance understanding pathogenesis points new targets investigation. We consider implications context existing genetic potential need reassess diagnostic boundaries neuropsychiatric disorders before discussing ways forward directed mechanistic develop stratified, novel therapeutic approaches future.