Neurotoxic Vulnerability Underlying Schizophrenia Spectrum Disorders

Neurotoxic vulnerability that putatively contributes to the etiopathogenesis of schizophrenia spectrum disorders encompasses perinatal adversity, genetic linkage, epigenetic disadvantage and neurodegenerative propensities that affect both symptom domains, positive, negative and cognitive, and biomarkers of the disorder. Molecular and cellular apoptosis/excitotoxicity that culminates in regional brain loss, reductions in reelin expression, trophic disruption, perinatal adversity, glycogen synthase kinase-3 dysregulation and various instances of oxidative stress all influence the final end-point disorder. The existence of prodromal psychotic phases, structural-functional aspects of regional neuroimaging, dopamine signal overexpression and psychosis propensity provide substance for neurodegenerative influences. The pathophysiology of schizophrenia spectrum disorder encompasses the destruction of normal functioning of the neurotrophins, in particular brain-derived neurotrophic factor (BDNF), dyskinesia of necessary movements, and metabolic-metabolomic and proteomic markers. Neurotoxic accidents combined with genetic susceptibility appears to play a role in interfering normal neurodevelopment or in the tissue-destructive neurodegeneration or both, thereby elevating the eventual risk for disorder tendencies and eventual expression.