On a Quest for the Elusive Schizophrenia Biomarker

  • Zafiris J. Daskalakis
    Address correspondence to Zafiris J. Daskalakis, M.D., Ph.D., F.R.C.P.(C.), Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada
    Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
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      There is a desperate need to identify biomarkers for psychiatric illness. Biomarkers facilitate the development of etiologic rather than symptom-based diagnostic methods, foster early identification and treatment, and advance our understanding of the complex genetic and neurobiological mechanisms involved in psychiatric disorders. Biomarkers also reflect a genetic predisposition to a disorder with or without phenotypic evidence for the disorder (
      • Turetsky B.I.
      • Calkins M.E.
      • Light G.A.
      • Olincy A.
      • Radant A.D.
      • Swerdlow N.R.
      Neurophysiological endophenotypes of schizophrenia: The viability of selected candidate measures.
      ). Schizophrenia is one of the most severe neuropsychiatric disorders, the diagnosis of which remains symptom-based, not etiologically based. Moving to more etiologically based diagnostic methods is preferable for disorder identification compared with the status quo of relying on subjective symptom reports and observation. True biomarkers should also facilitate identification and treatment of a population at high risk for the disorder, which may ultimately translate into prevention in a subset of individuals. Furthermore, biomarkers also provide an entry point from which to study the molecular mechanisms underlying schizophrenia that may lead to new treatments. Lastly, although the heritability of schizophrenia has been estimated to be as high as 80% (
      • Owen M.J.
      • O'Donovan M.C.
      • Gottesman I.I.
      ), it is now clear that the genetics of schizophrenia are complex, with many susceptibility genes and epigenetic, stochastic, and nongenetic (i.e., environmental) influences. Biomarkers may uncover further variants in the structural genome by avoiding the heterogeneity that exists when relying exclusively on clinical presentation.
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