Objective: Recognizing the prodrome of a first psychotic episode prospectively creates the opportunity of intervention, which could delay, ameliorate or even prevent onset. Valid criteria and a reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, the Comprehensive Assessment of At-Risk Mental States (CAARMS), which has been designed for such a purpose. It has two functions: (i) to assess psychopathology thought to indicate imminent development of a first-episode psychotic disorder; and (ii) to determine if an individual meets criteria for being at ultra high risk (UHR) for onset of first psychotic disorder. This paper describes the pilot evaluation of the CAARMS.Method: Several methodologies were used to test the CAARMS. First, CAARMS scores in a group of UHR young people and the association between CAARMS scores and the risk of transition to psychotic disorder, were analysed. Second, CAARMS scores in a UHR group were compared to a control group. To asses...

Mapping the onset of psychosis: the Comprehensive Assessment of At-Risk Mental States

As the number of studies related to the early identification of and intervention in the schizophrenia prodrome continues to grow, it becomes increasingly critical to develop methods to diagnose this new clinical entity with validity. Furthermore, given the low incidence of patients and the need for multisite collaboration, diagnostic and symptom severity reliability is also crucial. This article provides further data on these psychometric parameters for the prodromal assessment instruments developed by the Prevention through Risk Identification, Management, and Education (PRIME) prodromal research team at Yale University: the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms. It also presents data suggesting that excellent interrater reliability can be established for diagnosis in a day-and-a-half-long training workshop.

https://cdr.lib.unc.edu/downloads/b5644t84j

Prodromal Assessment With the Structured Interview for Prodromal Syndromes and the Scale of Prodromal Symptoms: Predictive Validity, Interrater Reliability, and Training to Reliability

Context Early detection and prospective evaluation of individuals who will develop schizophrenia or other psychotic disorders are critical to efforts to isolate mechanisms underlying psychosis onset and to the testing of preventive interventions, but existing risk prediction approaches have achieved only modest predictive accuracy. Objectives To determine the risk of conversion to psychosis and to evaluate a set of prediction algorithms maximizing positive predictive power in a clinical high-risk sample. Design, Setting, and Participants Longitudinal study with a 2½-year follow-up of 291 prospectively identified treatment-seeking patients meeting Structured Interview for Prodromal Syndromes criteria. The patients were recruited and underwent evaluation across 8 clinical research centers as part of the North American Prodrome Longitudinal Study. Main Outcome Measure Time to conversion to a fully psychotic form of mental illness. Results The risk of conversion to psychosis was 35%, with a decelerating rate of transition during the 2½-year follow-up. Five features assessed at baseline contributed uniquely to the prediction of psychosis: a genetic risk for schizophrenia with recent deterioration in functioning, higher levels of unusual thought content, higher levels of suspicion/paranoia, greater social impairment, and a history of substance abuse. Prediction algorithms combining 2 or 3 of these variables resulted in dramatic increases in positive predictive power (ie, 68%-80%) compared with the prodromal criteria alone. Conclusions These findings demonstrate that prospective ascertainment of individuals at risk for psychosis is feasible, with a level of predictive accuracy comparable to that in other areas of preventive medicine. They provide a benchmark for the rate and shape of the psychosis risk function against which standardized preventive intervention programs can be compared.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/482556/yoa70062_28_37.pdf

Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America.

CONTEXT: A major limitation on the development of biomarkers and novel interventions for schizophrenia is that its pathogenesis is unknown. Although elevated striatal dopamine activity is thought to be fundamental to schizophrenia, it is unclear when this neurochemical abnormality develops in relation to the onset of illness and how this relates to the symptoms and neurocognitive impairment seen in individuals with prodromal symptoms of schizophrenia. OBJECTIVES: To determine whether striatal dopamine function is elevated in individuals with prodromal symptoms of schizophrenia before the onset of psychosis and to assess how this relates to the symptoms and neurocognitive impairment. DESIGN: Case-control study of in vivo striatal dopaminergic function. SETTING: Academic research. Patients Patients were recruited from a community mental health service. Twenty-four patients having prodromal symptoms of schizophrenia were compared with 7 patients having schizophrenia and with 12 matched healthy control subjects from the same community. Main Outcome Measure Striatal 6-fluoro-l-dopa F 18-dopa uptake measured using positron emission tomographic (18)F-dopa imaging. RESULTS: Striatal (18)F-dopa uptake was elevated in patients with prodromal symptoms of schizophrenia (effect size, 0.75) to an intermediate degree compared with that in patients with schizophrenia (effect size, 1.25). The elevation was localized in the associative striatum in both groups. Moreover, striatal (18)F-dopa uptake in patients with prodromal symptoms of schizophrenia was correlated with the severity of prodromal psychopathologic and neuropsychological impairment but not with the severity of anxiety or depressive symptoms. CONCLUSIONS: These findings indicate that dopamine overactivity predates the onset of schizophrenia in individuals with prodromal psychotic symptoms, is predominantly localized in the associative striatum, and is correlated with the severity of symptoms and neurocognitive dysfunction.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/482943/yoa80079_13_20.pdf

Elevated Striatal Dopamine Function Linked to Prodromal Signs of Schizophrenia

Context Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. Objective To develop a differential predictive clinical model of transition to first-episode psychosis. Design Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. Setting Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. Participants Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom–based criterion cognitive disturbances (COGDIS). Main Outcome Measure Incidence of transition to psychosis. Results At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. Conclusions The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

/pdf/prediction-of-psychosis-in-adolescents-and-young-adults-at-2v9zjdrcse.pdf

Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study

OBJECTIVE: This study was conducted to determine the interrater reliability and predictive validity of a set of diagnostic criteria for the prodrome of the first episode of schizophrenic psychosis when based on the Structured Interview for Prodromal Syndromes. METHOD: The subjects were patients referred for evaluation because of a suspected schizophrenia prodromal syndrome. For the reliability study, two to four raters independently diagnosed 18 patients on the basis of face-to-face or videotaped interviews. For the validity study, 6- and 12-month outcome data were collected for 29 patients. RESULTS: Agreement in differentiating prodromal from nonprodromal patients was 93%. The prodromal features had converted to schizophrenic psychosis for 46% of the prodromal patients at 6 months and for 54% at 12 months. CONCLUSIONS: In small groups of subjects, these diagnostic criteria for the schizophrenic prodrome and the Structured Interview for Prodromal Syndromes showed promising interrater reliability and predi...

/pdf/prospective-diagnosis-of-the-initial-prodrome-for-1xzws4drpg.pdf

Prospective Diagnosis of the Initial Prodrome for Schizophrenia Based on the Structured Interview for Prodromal Syndromes: Preliminary Evidence of Interrater Reliability and Predictive Validity

Duration of untreated psychosis (DUP), the period between psychosis onset and entry into care, is a time of great vulnerability. Longer DUP predicts poorer outcomes, and delayed treatment access can limit the effectiveness of coordinated specialty care (CSC) services. This column details one component of a broader early detection campaign, a quality improvement intervention focusing on reducing the delay between confirmation of eligibility and admission to care within a benchmark period of 7 days. Median delay significantly fell (from 13.5 to 3 days), and the proportion of admissions that met the benchmark increased (from 33% to 71%) over 4 years. This intervention provides a sustainable model to reduce wait times at CSC services.

Philip J. Markovich

Papers

Prospective Diagnosis of the Initial Prodrome for Schizophrenia Based on the Structured Interview for Prodromal Syndromes: Preliminary Evidence of Interrater Reliability and Predictive Validity

Reducing Delay From Referral to Admission at a U.S. First-Episode Psychosis Service: A Quality Improvement Initiative.