Duration of the psychosis prodrome

The recognition of a prodromal period preceding the onset of frank psychosis dates back to its first descriptions. Despite insights gained from a prospective approach to the study of the Clinical High Risk syndrome for psychosis (CHR-P), a prospectively-based understanding of the duration of the psychosis prodrome and the factors that may influence is not well-established. Here we analyze data from the second North American Prodrome Longitudinal Study (NAPLS-2) to characterize prodrome duration in those who converted to psychosis. Of the 764 participants identified as being at CHR-P, 94 converted to psychosis and 92 of these had recorded estimates of prodrome onset. Estimates of prodrome duration were derived from CHR-P syndrome onset and conversion dates from the Structured Interview for Psychosis-risk Syndromes. Results identified a mean prodrome duration of 21.6 months. Neither CHR-P sub-syndrome nor medication exposure was found to significantly influence prodrome duration in this sample. These results provide the most precise estimate of prodrome duration to date, although results are limited to prodromes identified by ascertainment as being at CHR-P. Our findings also suggest a rule of thirds with regard to prodrome duration in those followed for two years: one third of CHR-P patients who convert will do so by 1 year after CHR-P syndrome onset, another third 1–2 years after onset, and the final third more than 2 years after onset

Lack of diagnostic pluripotentiality in patients at clinical high risk for psychosis: Specificity of comorbidity persistence and search for pluripotential subgroups

More than 20 years after the clinical high risk syndrome for psychosis (CHR) was first articulated, it remains controversial whether the CHR syndrome predicts onset of psychosis with diagnostic specificity or predicts pluripotential diagnostic outcomes. Recently, analyses of observational studies, however, have suggested that the CHR syndrome is not pluripotential for emergent diagnostic outcomes. The present report conducted additional analyses in previously reported samples to determine (1) whether comorbid disorders were more likely to persist in CHR patients compared to a comparison group of patients who responded to CHR recruitment efforts but did not meet criteria, termed help-seeking comparison subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups could be identified. All data were derived from 2 multisite studies in which DSM-IV structured diagnostic interviews were conducted at baseline and at 6-month intervals. Across samples we observed persistence of any nonpsychotic disorder in 80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with persistence of anxiety, depressive, and bipolar disorders considered separately were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful. These findings add additional support to the view that the CHR syndrome is not pluripotential for predicting various diagnostic outcomes but rather is specific for predicting emergent psychosis

Predictive validity of conversion from the clinical high risk syndrome to frank psychosis

Although the clinical high risk for psychosis (CHR) paradigm has become well-established over the past two decades, one key component has received surprisingly little investigative attention: the predictive validity of the criteria for conversion or transition to frank psychosis. The current study evaluates the predictive validity of the transition to psychosis as measured by the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR individuals. Participants included 33 SIPS converters and 399 CHR non-converters both from the North American Prodromal Longitudinal Study (NAPLS-2), as well as a sample of 67 separately ascertained first-episode psychosis (FEP) patients from the STEP program. Comparisons were made at baseline and one-year follow-up on demographic, diagnostic stability (SCID), and available measurement domains relating to severity of illness (psychotropic medication, psychosocial treatment, and resource utilization). Principal findings are: 1) a large majority of cases in both SIPS converters (n = 27/33, 81.8%) and FEP (n = 57/67, 85.1%) samples met criteria for continued psychosis at one-year follow-up; 2) follow-up prescription rates for current antipsychotic medication were higher in SIPS converters (n = 17/32, 53.1%) compared to SIPS non-converters (n = 81/397, 20.4%), and similar as compared to FEP cases (n = 39/65, 60%); and 3) at follow-up, SIPS converters had higher rates of resource utilization (psychiatric hospitalizations, day hospital admissions, and ER visits) than SIPS non-converters and were similar to FEP in most categories. The results suggest that the SIPS definition of psychosis onset carries substantial predictive validity. Limitations and future directions are discussed

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

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

The association between migrant status and transition in an ultra-high risk for psychosis population

Purpose: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. Methods: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. Results: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147–756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62–1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70–1.51). Conclusions: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics

Aetiological investigations in early developmental impairment: are they worth it?

OBJECTIVE: To study the frequency a diagnosis is made in children with early developmental impairment (EDI), and the contribution made to diagnosis by specific investigations. DESIGN: Retrospective case note review. SETTING: Community, neurodisability and neurology department at a UK tertiary centre. PARTICIPANTS: Children referred to determine the aetiology of EDI where a cause was not evident on history and examination. Participants were divided into two groups: EDI and no additional features (EDI-) and EDI with additional features (EDI+). MAIN OUTCOME MEASURES: The frequency a cause was found for the child's EDI and which tests contributed to a diagnosis. RESULTS: 699 participants, 68.8% boys, median age at investigation 2 years 8 months (range 3 months to 11 years 5 months). 61 (8.7%) of participants had no investigations, and children with EDIâˆ' were less likely to be investigated (χ(2)=12.5, p<0.05). A diagnosis was made in 166 children (23.7%) and was more frequent in EDI+ (EDI- 9.9%, EDI+ 27.3%, χ(2)=19.0; p<0.05). Full blood count, zinc protoporphyrin, renal or liver function, bone profile, biotinidase, creatine kinase or lead level revealed no diagnoses. The following investigations found causes for EDI: MRI (23.1%), microarray (11.5%), Fragile X (0.9%), plasma amino acids (1.2%), urine organic acids (0.9%) and thyroid function tests (0.5%). CONCLUSIONS: The majority of 'screening' investigations for EDI do not contribute to a diagnosis, highlighting an area of cost saving for the NHS and reduced burden for patients and families. We propose a streamlined guideline for the investigation of EDI based on our data