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On a Quest for the Elusive Schizophrenia Biomarker

  • Zafiris J. Daskalakis
    Correspondence
    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
    Affiliations
    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.
      Schizophrenia.
      ), 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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      References

        • 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.
        Schizophr Bull. 2007; 33: 69-94
        • Owen M.J.
        • O'Donovan M.C.
        • Gottesman I.I.
        Schizophrenia.
        in: McGuffin P. Owen M.J. Gottesman I.I. Psychiatric Genetics and Genomics. Oxford University Press, Oxford2002: 247-266
        • Gottesman I.I.
        • Gould T.D.
        The endophenotype concept in psychiatry: etymology and strategic intentions.
        Am J Psychiatry. 2003; 160: 636-645
        • Benes F.M.
        • McSparren J.
        • Bird E.D.
        • SanGiovanni J.P.
        • Vincent S.L.
        Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients.
        Arch Gen Psychiatry. 1991; 48: 996-1001
        • Akbarian S.
        • Kim J.J.
        • Potkin S.G.
        • Hagman J.O.
        • Tafazzoli A.
        • Bunney Jr, W.E.
        • et al.
        Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics [see comments].
        Arch Gen Psychiatry. 1995; 52 (discussion 267–278): 258-266
        • Hasan A.
        • Wobrock T.
        • Grefkes C.
        • Labusga M.
        • Levold K.
        • Schneider-Axmann T.
        • et al.
        Deficient inhibitory cortical networks in antipsychotic-naive subjects at risk of developing first-episode psychosis and first-episode schizophrenia patients: A cross-sectional study.
        Biol Psychiatry. 2012; 72: 744-751
        • Liu S.K.
        • Fitzgerald P.B.
        • Daigle M.
        • Chen R.
        • Daskalakis Z.J.
        The relationship between cortical inhibition, antipsychotic treatment, and the symptoms of schizophrenia.
        Biol Psychiatry. 2009; 65: 503-509
        • Lewis D.A.
        • Hashimoto T.
        • Volk D.W.
        Cortical inhibitory neurons and schizophrenia.
        Nat Rev Neurosci. 2005; 6: 312-324
        • Richter M.A.
        • de Jesus D.R.
        • Hoppenbrouwers S.
        • Daigle M.
        • Deluce J.
        • Ravindran L.N.
        • et al.
        Evidence for cortical inhibitory and excitatory dysfunction in obsessive compulsive disorder.
        Neuropsychopharmacology. 2012; 37: 1144-1151
        • Greenwood T.A.
        • Braff D.L.
        • Light G.A.
        • Cadenhead K.S.
        • Calkins M.E.
        • Dobie D.J.
        • et al.
        Initial heritability analyses of endophenotypic measures for schizophrenia: The consortium on the genetics of schizophrenia.
        Arch Gen Psychiatry. 2007; 64: 1242-1250

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