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Identifying an elusive target with the help of an unproven technique

Molecular Psychiatry volume 26, pages 7074–7075 (2021)Cite this article

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Schizophrenia is a chronic, developmental disease which affects all aspects of social, family and vocational life, hence the search for prediction enabling prevention is well justified. To enable this, it is essential to define a population at risk and intervene before, or very early in the course of the illness, before irreparable damage occurs. For example, treating metabolic syndrome preceding predicting later myocardial infarction, or early identification and treatment of stroke.

In schizophrenia, premorbid/prodromal manifestations characterize the population at risk, and transition into the first psychotic episode is considered the milestone event to be predicted and prevented. Delayed development [1], clumsy motor behavior in toddlers [2], poor scholastic achievements, mild cognitive, and social impairment in adolescents [3] are premorbid/prodromal manifestations more common in future patients. However, these are too common in the general population of children and adolescents to enable prediction. Pioneering, diligent research in the early 1990s [4] attempted to narrow-down and crystalize these risk factors, defining the ultra-high risk (UHR) clinical criteria including attenuated and/or brief psychotic symptoms, and/or decreased social/vocational functioning in a person with a first degree relative with schizophrenia. Although initial studies using these UHR criteria were successful in identifying one in four future patients, more recent studies using the same criteria identify fewer than 10% of individuals reaching the milestone event [5]. Among the reasons for this relatively low rate of predictive accuracy are the presence of attenuated or brief psychotic symptoms in 10–20% of normal, un-diagnosed people, particularly adolescents and young adults, the typical age of onset of psychotic disorders [6]. Attenuated or brief psychotic symptoms are also present in other, non-psychotic disorders such as anxiety, affective disorder, ADHD or personality disorders. Furthermore, these symptoms are typically transient and improve over time, as do social and role functioning [7]. In addition, the timing and precise characterization of transition into psychosis is not easy to define. For all of these reasons, clinical criteria alone do not enable prediction or prevention.

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References

  1. Jones P, Rodgers B, Murray R, Marmot M. Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet. 1994;344:1398–402.

    Article  CAS  Google Scholar 

  2. Schiffman J, Walker E, Ekstrom M, Schulsinger F, Sorensen H, Mednick S. Childhood videotaped social and neuromotor precursors of schizophrenia: a prospective investigation. Am J Psychiatry. 2004;161:2021–7.

    Article  Google Scholar 

  3. Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents. Am J Psychiatry. 1999;156:1328–35.

    CAS  PubMed  Google Scholar 

  4. Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rossler A, Schultze-Lutter F, et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013;70:107–20.

    Article  Google Scholar 

  5. Formica M, Phillips L, Hartmann J, Yung A, Wood S, Lin A et al. Has improved treatment contributed to the declining rate of transition to psychosis in ultra-high-risk cohorts? Schizophrenia Res. 2020.

  6. Werbeloff N, Drukker M, Dohrenwend BP, Levav I, Yoffe R, van Os J, et al. Self-reported attenuated psychotic symptoms as forerunners of severe mental disorders later in life. Arch Gen Psychiatry. 2012;69:467–75.

    Article  Google Scholar 

  7. Addington J, Cornblatt BA, Cadenhead KS, Cannon TD, McGlashan TH, Perkins DO, et al. At clinical high risk for psychosis: outcome for nonconverters. Am J Psychiatry. 2011;168:800–5.

    Article  Google Scholar 

  8. Perkins DO, Olde Loohuis L, Barbee J, Ford J, Jeffries CD, Addington J, et al. Polygenic risk score contribution to psychosis prediction in a target population of persons at clinical high risk. Am J Psychiatry. 2020;177:155–63.

    Article  Google Scholar 

  9. Chung Y, Allswede D, Addington J, Bearden CE, Cadenhead K, Cornblatt B, et al. Cortical abnormalities in youth at clinical high-risk for psychosis: Findings from the NAPLS2 cohort. Neuroimage Clin. 2019;23:101862.

    Article  Google Scholar 

  10. Johnstone E, Frith C, Crow T, Husband J, Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet. 1976;308:924–26.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Sheba Medical Center, Tel Hashomer, Israel

    Mark Weiser

  2. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Mark Weiser

  3. Nicosia University School of Medicine, Nicosia, Cyprus

    Michael Davidson

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Correspondence to Mark Weiser.

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Dr WM has received payment for advisory boards/ fees/speaker fees/performed PANSS training from Teva, Jansen, Dexel and Lundbeck. Dr DM is an employee and owns stock options of Minerva Neurosciences, a Biotech developing CNS drugs.

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Weiser, M., Davidson, M. Identifying an elusive target with the help of an unproven technique. Mol Psychiatry 26, 7074–7075 (2021). https://doi.org/10.1038/s41380-021-01213-y

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