Gene Variant Related Neurological and Molecular Biomarkers Predict Psychosis Progression, with Potential for Monitoring and Prevention

The (<i>MTHFR)</i> C677T gene polymorphism is associated with neurological disorders and schizophrenia. Patients diagnosed with schizophrenia and schizoaffective disorder and controls (<i>n</i> 134) had data collected for risk factors, molecular and neuro-sensory variables, symptoms, and functional outcomes. Promising gene variant-related predictive biomarkers were identified for diagnosis by Receiver Operating Characteristics and for illness duration by linear regression. These were then analyzed using Spearman's correlation in relation to the duration of illness. Significant correlations were ranked by strength and plotted on graphs for each <i>MTHFR</i> C677T variant. Homozygous <i>MTHFR</i> 677 TT carriers displayed a mid-illness switch to depression, with suicidality and a late-phase shift from lower to higher methylation, with activated psychosis symptoms. <i>MTHFR</i> 677 CC variant carriers displayed significant premorbid correlates for family history, developmental disorder, learning disorder, and head injury. These findings align with those of low methylation, oxidative stress, multiple neuro-sensory processing deficits, and disability outcomes. Heterozygous <i>MTHFR</i> 677 CT carriers displayed multiple shifts in mood and methylation with multiple adverse outcomes. The graphically presented ranked biomarker correlates for illness duration allow a perspective of psychosis development across gene variants, with the potential for phase of illness monitoring and new therapeutic insights to prevent or delay psychosis and its adverse outcomes.