Research in people with psychosis risk syndrome: a review of the current evidence and future directions

Abstract

After decades of research, schizophrenia and related psychotic disorders are still among the most debilitating disorders in medicine. The chronic illness course in most individuals, greater treatment responsiveness during the first episode, progressive grey matter decline during early disease stages, and retrospective accounts of "prodromal" or early illness signs and symptoms formed the basis for research on the psychosis risk syndrome,, known variably as "clinical high risk"(CHR), or "ultra-high risk" (UHR), or "prodromal". The pioneering era of research on the psychosis risk syndrome focused on the development and validation of specific assessment tools and the delineation of high risk criteria. This was followed by the examination of conversion rates in psychosis risk cohorts followed naturalistically, identification of predictors of conversion to psychosis, and investigation of interventions able to abort or delay the development of full psychosis. Despite initially encouraging results concerning the predictive validity of the psychosis risk syndrome criteria, recent findings of declining conversion rates demonstrate the need for further investigations. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioral therapy, are encouraging, but are currently still insufficient to make treatment recommendations for this early, relatively non-specific illness phase. The next phase of research on the psychosis risk syndrome just now beginning, has moved to larger, "multi-site" projects to increase generalizability and to ensure that sufficiently large samples at true risk for psychosis are included. Emphasis in these emerging studies is on: 1) identification of biomarkers for conversion to psychosis; 2) examination of non-antipsychotic, neuroprotective and low-risk pharmacologic and non-pharmacologic interventions; 3) testing of potentially phase-specific interventions; 4) examination of the relationship between treatment response during yhre of psychosis risk syundrome and prognosis for the course of illness; 5) follow-up of patients who developed schizophrenia despite early interventions and comparison of illness trajectories with patients who did not receive early interventions; 6) characterization of individuals with outcomes other than schizophrenia spectrum disorders, including bipolar disorder and remission from the psychosis risk syndrome, including false positive cases; 7) assessment of Corresponding Author: Christoph U. Correll, MD, The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, NY 11004, USA; telephone: 718-470-4812; fax: 718-343-1659; ccorrell@lij.edu. Financial Disclosure: Dr. Correll has been a consultant or Data Safety Monitoring Board member to or has received honoraria from Actelion, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GSK, Hoffman-La Roche, Lundbeck, OrthoMcNeill-Janssen/J&J, Medicure, Otsuka, Pfizer, Schering-Plough, Supernus and Vanda, and has served on the speaker's bureau of AstraZeneca, BristolMyers...

Decreased pain sensitivity among people with schizophrenia

“…The authors found a greater BOLD response in patients in the primary sensory-discriminative pain processing region (S1) compared to controls, and noticed reduced activity in the posterior cingulate cortex, insula and brain stem, suggesting abnormal central processing during painful stimuli. Taken together, these findings suggest decreased pain sensitivity as a potential endophenotype of schizophrenia, which may be relevant to enhance diagnostic precision in general, or predictive validity during the ultra-high risk syndrome for psychosis [9]. Furthermore, studies should investigate if symptomatic response to antipsychotic treatment is related to a normalization of pain sensitivity and/or if baseline values could be predictive of future symptomatic response.…”

Clinical characteristics and influence of childhood trauma on the prodrome of bipolar disorder

“…Symptom frequency is rated as 1 = infrequent, 2 = recurrent, 3 = very frequent, or 4 = static lifetime or character trait. Consistent with conventions used for the psychotic prodrome, 25 symptoms were included in the analysis if they were of at least moderate severity and were not considered a character trait, unless the severity had increased by at least one point before the onset of the disorder. Regarding onset pattern, the prodrome was classified as acute (o 1 month in duration), subacute (1-12 months in duration), or insidious (4 1 year in duration).…”

Delays in Treatment: A Literature Review of Pathways to Treatment for Psychosis

“…A prodromal period is a period of functional decline in individuals (i.e., social withdrawal, fluctuations in thinking, avolition, etc.) preceding more severe symptoms (i.e., acute psychosis) such as hallucinations and delusions that the DUP figure captures (Correll, et al, 2010). During the search in the literature, little evidence showed researchers considered this phase into their calculations of average delay in treatment.…”

“…At the level of the individual are educational, social, and vocational opportunities that can be cut short because of the illness's debilitating effects. Numerous qualitative studies in the literature reveal such costs as key themes when researching individuals (Bay et al, 2016;Connor et al, 2016;Correll, C. U. et al, 2010;Melton & Blajeski, 2017). The same researchers hypothesize that early intervention can reduce and even eliminate these costs if treatment is given early enough.…”

“…Individuals who develop psychosis may experience symptoms such as visual and auditory hallucinations, delusions of grandeur, paranoia, social isolation, school disengagement, lack of appetite, poverty of speech, perseveration, catatonia, and other psychomotor or cognitive alterations (Correll et al, 2010;Melton & Blajeseki, 2017). Main causes of psychosis include substance abuse, schizophrenia, lack of sleep, postpartum depression, and severe stress.…”