Stephanie Fryar-Williams
University of Adelaide, Australia
Title: Translational biomarker cross-talk between biochemistry and sensory-process in schizophrenia and schizo-affective disorder
Biography
Biography: Stephanie Fryar-Williams
Abstract
Background: The Mental Health Biomarker Project (2010-2014), selected commercially-available biochemistry markers related to monoamine biochemistry and measures for visual and auditory processing pathways, to investigate biomarkers for schizophrenia and schizoaffective disorder and their translational relationships. Methods: Within a case-control design with multiple exclusion criteria designed to exclude organic causes and confounding variables, 67 independently DSM diagnosed and 67 undiagnosed participants from a defined hospital, clinic and community catchment area were investigated for 30 biochemical and neuro--sensory putative markers. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection and sensory-processing assessment. Outcome measures were analysed from blood and urine samples for monoamine neurotransmitters and vitamins, cofactors and intermediate-substances known to be related to oxidative stress and the synthesis and metabolism of monoamines. Neurocognitive assessment of visual and auditory processing was conducted at both peripheral and central levels. Data analysis by Receiver Operating Curve (ROC), Spearmans correlation, odds ratio of association and Lowess regression translational potential analysis. Results: 21 putative markers, divided into six domains, demonstrated biomarker status for schizophrenia and schizoaffective disorder on ROC analysis. Five rankings of biomarker domains were determined based upon ROC, correlative and odds ratio strengths. On translational analysis biomarkers of lesser strength in the cellular nutrition and biochemistry domain were found to demonstrate a powerful pervasive influence on all other biomarker domains of influence within the structure of schizophrenia. Analyzing inter-domain translational influences in relationship to ranked domain strengths gives evidence of a circular dynamic process whereby primary sensory processing impairment due to neuronal damage at a cellular level activates the hypothalamic pituitary adrenal axis that sets in place a vicious cycle of further-compromised cellular biochemistry leading to further catecholamine elevation with immune activation, oxidative stress and sensory processing dysconnectivity. Conclusions: There is scope for pioneering investigation of specific biological and neuro-cognitive-sensory biomarkers to be useful for identification of schizophrenia and schizoaffective disorder. Peripheral and central sensory processing deficits, oxidative stress, catecholamine elevation and nutritional biochemistry disorders contribute to the aetiology of psychosis in schizophrenia and schizo-affective disorder. In translational terms, nutritional biochemical factors, accumulate and translationally interact in stronger, more pervasive role than historically recognised, triggering a cascade of sensory processing deficits that activate the hypothalamic pituitary axis in a vicious cycle leading to dysconnectivity and psychosis..