Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit
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.
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2022, European NeuropsychopharmacologyCitation Excerpt :In general, healthcare operators should focus on patients’ preferences and priorities on the level of knowledge that they would like to receive. Methods of disclosing at-risk designations (Mittal et al., 2015; Sisti and Calkins, 2016; Woods et al., 2021) that match cultural preference toward the type of disclosure of risk should be better developed elucidating the variable stakeholder perceptions (Mittal et al., 2015). For example, pilot studies showed that sharing results with clinicians and not with the patients can allow for nuanced and personalised communication of risk in the context of clinical care (Oliver et al., 2020).