Elsevier

Schizophrenia Research

Volume 227, January 2021, Pages 10-17
Schizophrenia Research

Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit

https://doi.org/10.1016/j.schres.2020.04.020Get rights and content

Abstract

Background

Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis.

Method

Response to points of critique.

Results

We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not “extremely difficult”; e) the pattern of progression, although heterogenous, is discernible; f) “psychosis-like symptoms” are common but are not used to identify CHR; and g) on the point described as ‘the real risk,’ CHR diagnosis does not frequently cause harmful stigma.

Discussion

Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the “real risk” of stigma associated with a CHR “label,” however, our view is that avoiding words like “risk” and “psychosis” reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.

Section snippets

Must we fully understand disease mechanisms before we try to help?

Malhi et al. assert that we do not understand the causes and pathophysiology of psychiatric illness to the extent we do medical illnesses such as ischemic heart disease, which we will not dispute. We do not dispute either that “much remains unknown about the biology, aetiology and progression of these syndromes”; however, in our view it does not follow that “the application of early intervention for psychiatric disorders is clearly hamstrung.” Just as molecular understanding of ischemic heart

Is there an absence of reliable biomarkers for etiology and progression of psychosis?

Although what the authors mean by reliable is unclear, it is in fact the case that there are few FDA-registered biomarkers in neurology and none in psychiatry (or in CHR); however, Malhi et al. have pessimistically interpreted a snapshot taken during a period of rapid progress. For example, genomic insights into etiology (Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014; Sekar et al., 2016) and risk prediction for psychosis using polygenic scores (Perkins et al., 2020)

Are the symptoms used to identify CHR not specific to psychotic illnesses?

Patients who meet CHR criteria do not all progress to psychosis or to any single psychiatric diagnosis. This is very much analogous to patients with mild cognitive impairment (MCI) who may progress to Alzheimer's disease, Lewy body or vascular dementia, some combination, or who might not progress at all. In fact, the 15% rate of conversion from CHR to psychosis at one year in a recent meta-analysis (Salazar de Pablo et al., 2020) is comparable to the annualized conversion rate from MCI to

Is CHR diagnosis extremely difficult?

We first note that the CHR syndrome is either a research diagnosis or an innovative clinical one, not one endorsed as independently codable either in DSM-5 or ICD-10. Its status in DSM-5 (as Attenuated Psychosis Syndrome, APS) is somewhat ambiguous, described both as a “Condition for Further Study” (page 783) and also as one of four examples under the codable “Other Specified Schizophrenia Spectrum and Other Psychotic Disorder” (page 122) (American Psychiatric Association, 2013).

Malhi et al.

Does psychotic disorder lack a discernible pattern of progression?

Malhi et al. assert that “psychiatric illnesses do not appear to have a discernible pattern of progression in severity.” In the case of CHR, the evidence for a pattern of progression is actually quite strong, beginning with nonspecific symptoms such as anxiety and depression, followed by negative symptoms, and then by the more specific positive symptoms (Hafner et al., 1993). Most of the evidence on the early course comes from retrospective studies, since prospective population cohort studies

Are psychosis-like symptoms relatively common among non-psychotic individuals?

“Psychosis-like” symptoms or experiences (PLEs) are assessed by self-report. Malhi et al. recapitulate a common error (Schultze-Lutter et al., 2018a) by conflating PLEs with the clinician-assessed attenuated positive symptoms used to diagnose CHR, which unlike PLEs employ an experienced and trained clinician to distinguish pathological from non-pathological experiences. Studies comparing self-report vs interview methods consistently find that rates of attenuated positive symptoms in the CHR

Is confusion and inconsistency hindering CHR research and practice?

Malhi et al. discuss three examples of different nomenclature used to capture youth and young adults at-risk for psychosis: Ultra High Risk (UHR), At-Risk Mental State (ARMS), and Clinical High Risk (CHR), and they comment that at least the term CHR is used in somewhat different ways across research groups, with for example some groups including the basic symptoms approach as fitting under CHR. On this last specific point, we note that many studies are careful to report results for basic

Have CHR researchers become complacent?

Malhi et al. speculate that the field may be possessed of “a false sense that accurate identification of prodromal psychosis is possible and has already been achieved,” which in turn “may foster complacency amongst researchers.” While we do feel some progress has been made in identifying which individuals with CHR are at higher and lower risk with clinically-based risk calculators (Cannon et al., 2016; Carrión et al., 2016; Osborne and Mittal, 2019; Zhang et al., 2018), we note that the

Does the CHR ‘label’ cause harmful stigma?

Malhi et al. are concerned that CHR diagnostic practices may harm patients more often than we realize by creating stigma and may even do more harm than good. There is no question that stigma is harmful or that psychiatric patients face stigma; similarly, there can also be no question that stigmatizing patients is unacceptable and inconsistent with the ethical principle of non-maleficence (Beauchamp and Childress, 2013) or “first do no harm.”

More salient questions, however, are whether, how

Conclusion

Overall, Malhi et al.'s arguments do not fairly characterize the state of progress in the CHR field nor efforts to minimize stigma by empathic discussion with patients and families about the meanings of psychiatric diagnosis and of risk. Despite their various points of critique, which we address above, Malhi et al. do not go so far as to conclude, however, that early intervention with CHR is sufficiently hamstrung and ethically precarious that we should stop trying to intervene early for

Role of the funding source

Preparation of this article was supported in part by US National Institute of Mental Health grants U01MH082022, R01MH121095, R01MH107250, U01MH081928, R01MH111448, K23MH116130, U01MH081857, R01MH105084, U01MH082004, U01MH081944, R01MH105243, U01MH081984, R01MH105178, K23MH115252, U01MH076989, R01MH113565, R01MH107558, R01MH115332, R01MH113533, R01MH112545, R01MH116039, R01MH120088, R01MH112612, R34MH110506, R01MH112613, R21MH119438, R33MH111850, R01MH119219, U01MH081902, R01MH112189, and

Contributors

All authors contributed to the drafting and editing of the manuscript.

Conflict of interest

Dr. Woods reports that he has received sponsor-initiated research funding support from Teva, Boehringer-Ingelheim, Amarex, and SyneuRx. He has consulted to Boehringer-Ingelheim, New England Research Institute, and Takeda. He has been granted US patent no. 8492418 B2 for a method of treating prodromal schizophrenia with glycine agonists. Dr. Hyman serves on the board of directors for Voyager Therapeutics, and on scientific advisory boards for Janssen, BlackThorn Therapeutics, F-Prime Capital,

Acknowledgement

The authors acknowledge the inestimable assistance of their staffs, who are on the front line of minimizing risks and maximizing benefits for individuals with CHR and their families.

References (106)

  • V.B. Perez et al.

    Automatic auditory processing deficits in schizophrenia and clinical high-risk patients: forecasting psychosis risk with mismatch negativity

    Biol. Psychiatry

    (2014)
  • M. Pruessner et al.

    Attenuated cortisol response to acute psychosocial stress in individuals at ultra-high risk for psychosis

    Schizophr. Res.

    (2013)
  • A. Ramyead et al.

    O33. EEG alpha event-related desynchronization deficits predict conversion to psychosis in individuals with the psychosis risk syndrome

    Biol. Psychiatry

    (2019)
  • S. Ruhrmann et al.

    Probably at-risk, but certainly ill - advocating the introduction of a psychosis spectrum disorder in DSM-V

    Schizophr. Res.

    (2010)
  • F. Schultze-Lutter et al.

    Comparing the prodrome of schizophrenia-spectrum psychoses and affective disorders with and without psychotic features

    Schizophr. Res.

    (2012)
  • F. Schultze-Lutter et al.

    Improving the clinical prediction of psychosis by combining ultra-high risk criteria and cognitive basic symptoms

    Schizophr. Res.

    (2014)
  • F. Schultze-Lutter et al.

    EPA guidance on the early detection of clinical high risk states of psychoses

    European Psychiatry

    (2015)
  • A.G. Tabak et al.

    Prediabetes: a high-risk state for diabetes development

    Lancet

    (2012)
  • M.J. van Tricht et al.

    Reduced parietal P300 amplitude is associated with an increased risk for a first psychotic episode

    Biol. Psychiatry

    (2010)
  • N.D. Volkow et al.

    The conception of the ABCD study: from substance use to a broad NIH collaboration

    Developmental Cognitive Neuroscience

    (2018)
  • E.F. Walker et al.

    Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study

    Biol. Psychiatry

    (2013)
  • S.W. Woods et al.

    The case for including attenuated psychotic symptoms syndrome in DSM-5 as a psychosis risk syndrome

    Schizophr. Res.

    (2010)
  • J. Addington et al.

    North American Prodrome Longitudinal

    Schizophr. Res.

    (2020)
  • D.M. Allswede et al.

    Characterizing covariant trajectories of individuals at clinical high risk for psychosis across symptomatic and functional domains

    Am. J. Psychiatr.

    (2020)
  • American Medical Association

    AMA Principles of Medical Ethics

  • American Psychiatric Association

    Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

    (2013)
  • D.M. Anglin et al.

    Spontaneous labelling and stigma associated with clinical characteristics of peers ‘at-risk’ for psychosis

    Early Intervention in Psychiatry

    (2014)
  • A. Anticevic et al.

    Association of thalamic dysconnectivity and conversion to psychosis in youth and young adults at elevated clinical risk

    Jama Psychiatry

    (2015)
  • J. Baron et al.

    Experience of associative stigma in parents of adolescents at risk for psychosis

    Early Interv Psychiatry

    (2019)
  • T.L. Beauchamp et al.

    Principles of Biomedical Ethics

    (2013)
  • G. Bedi et al.

    Automated analysis of free speech predicts psychosis onset in high-risk youths

    NPJ Schizophr.

    (2015)
  • S. Benowitz

    To tell the truth: a cancer diagnosis in other cultures is often a family affair

    JNCI: Journal of the National Cancer Institute

    (1999)
  • M.E. Calkins et al.

    The psychosis spectrum in a young U.S. community sample: findings from the Philadelphia Neurodevelopmental Cohort

    World Psychiatry

    (2014)
  • T.D. Cannon et al.

    An individualized risk calculator for research in prodromal psychosis

    Am. J. Psychiatr.

    (2016)
  • H. Cao et al.

    Progressive reconfiguration of resting-state brain networks as psychosis develops: preliminary results from the North American Prodrome Longitudinal Study (NAPLS) consortium

    Schizophr. Res.

    (2019)
  • E.E. Carol et al.

    What are the implications of psychosis risk syndrome label? A diathesis-stress conceptualization

    Journal of Ethics in Mental Health

    (2018)
  • R.E. Carrión et al.

    Personalized prediction of psychosis: external validation of the NAPLS-2 psychosis risk calculator with the EDIPPP project

    Am. J. Psychiatr.

    (2016)
  • D.E. Clarke et al.

    DSM-5 field trials in the United States and Canada, part I: study design, sampling strategy, implementation, and analytic approaches

    Am. J. Psychiatr.

    (2013)
  • C.M. Corcoran

    Ethical and epidemiological dimensions of labeling psychosis risk

    AMA J. Ethics

    (2016)
  • C. Corcoran et al.

    Ethical issues in psychosis screening and prevention

    Journal of Ethics in Mental Health

    (2018)
  • C.M. Corcoran et al.

    Prediction of psychosis across protocols and risk cohorts using automated language analysis

    World Psychiatry

    (2018)
  • C. Davies et al.

    Lack of evidence to favor specific preventive interventions in psychosis: a network meta-analysis

    World Psychiatry

    (2018)
  • D.J. Dean et al.

    Motor clusters reveal differences in risk for psychosis, cognitive functioning, and thalamocortical connectivity: evidence for vulnerability subtypes

    Clin. Psychol. Sci.

    (2018)
  • J. Dugan et al.

    International classification of diseases, 10th revision, coding for diabetes

    Clin Diabetes

    (2017)
  • P. Fusar-Poli et al.

    Attenuated psychosis syndrome: ready for DSM-5.1?

    Annu. Rev. Clin. Psychol.

    (2014)
  • P. Fusar-Poli et al.

    At risk or not at risk? Meta-analysis of the prognostic accuracy of psychometric interviews for psychosis prediction

    World Psychiatry

    (2015)
  • P. Fusar-Poli et al.

    Disorder, not just state of risk: meta-analysis of functioning and quality of life in people at high risk of psychosis

    Br. J. Psychiatry

    (2015)
  • S.L. Fryer et al.

    Experience-dependent Strengthening of Auditory Prediction Signals in Youth at Clinical High Risk for Psychosis: Effects of Clinical Outcome and Conversion

  • P. Fusar-Poli et al.

    Heterogeneity of psychosis risk within individuals at clinical high risk: a meta-analytical stratification

    JAMA Psychiatry

    (2016)
  • P. Fusar-Poli et al.

    Toward s standard psychometric diagnostic interview for subjects at ultra high risk of psychosis: CAARMS versus SIPS

    Psychiatry Journal (Hindawi)

    (2016)
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