CASE PREDICTIVE and PROGNOSTIC BIOMARKERS FOR SCHIZOPHRENIA

Dr Stephanie Fryar-Williams. 1Youth in Mind Research Institute, Adelaide, SA, Australia. 2The Queen Elizabeth Hospital, Woodville, SA, Australia. 3Basil Hetzel Institute for Translational Health Research, Woodville, SA. 
Dr Graeme Tucker4 University of Adelaide, Adelaide, South Australia 
Dr Peter Clements4 University of Adelaide, Waite Research Institute, South Australia. 
Dr Yichao Huang 4 University of Adelaide, Waite Research Institute, South Australia
Dr Jörg Strobel 4 The University of Adelaide, Adelaide, South Australia.


Background:

Methylation plays a key role in regulating DNA expression and in regulating biochemistry pathways related to indole catecholamine synthesis and metabolism.
Enzymes in these pathways are also regulated by vitamin and trace element cofactors.

Objectives:
The primary objective was discover biomarkers for schizophrenia related to the main rate-limiting MTHFR C677T gene for methylation.

The secondary objective was to assess the predictive capacity of these biomarkers 

The tertiary objective was to integrate these markers with sensory processing markers to allow more comprehensive prediction and patient prognosis.
Materials and Methods:

67 well characterised non-acute cases from ward and community settings and 67 normal subjects had blood and urine testing for intermediate peptides and cofactors in biochemistry pathways associated the  MTHFR C677T gene.
Standardised neuro-physiological equipment was used for a range of visual and auditory sensory processing assessments.
Data analysis was by receiver operating (ROC) characteristics, Spearman’s correlation, logistic and linear regression with likelihood ratios, odds ratios and 95% confidence interval.
Results and Conclusions:
Methylation cofactors and their related catecholamine and oxidative stress levels achieved biomarker status and differentiated between  MTHFR 677 genotypes.

Genotype-dependent classification models achieved  90 - 95% % sensitivity and specificity for schizophrenia diagnosis, based upon blood and urine results, alone, 

Biomedical and sensory processing variables together predicted diagnosis  for MTHFR 677 genotypes with  92 - 100% sensitivity and specificity. 

The genotype-differentiated biomarkers related to different and generally contrasting trends in cofactor and catecholamine levels as well as sensory processing performance.
The genotype-differentiated biomarkers also predict severity, disability and cost-care burden for persons with schizophrenia. 
If validated in wider population, these findings have potential to enhance traditional symptom-based assessments. They also have implications for precision treatment approaches in schizophrenia and psychosis.

12 - CASE PREDICTIVE AND PROGNOSTIC BIOMARKERS FOR SCHIZOPHRENIA