Association of preceding psychosis risk states and non‐psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS‐2 cohort

Abstract

The validity and clinical utility of the concept of “clinical high risk” (CHR) for psychosis have so far been investigated only in risk‐enriched samples in clinical settings. In this population‐based prospective study, we aimed – for the first time – to assess the incidence rate of clinical psychosis and es­timate the population attributable fraction (PAF) of that incidence for preceding psychosis risk states and DSM‐IV diagnoses of non‐psychotic mental disorders (mood disorders, anxiety disorders, alcohol use disorders, and drug use disorders). All analyses were adjusted for age, gender and education. The incidence rate of clinical psychosis was 63.0 per 100,000 person‐years. The mutually‐adjusted Cox proportional hazards model indicated that preceding diagnoses of mood disorders (hazard ratio, HR=10.67, 95% CI: 3.12‐36.49), psychosis high‐risk state (HR=7.86, 95% CI: 2.76‐22.42) and drug use disorders (HR=5.33, 95% CI: 1.61‐17.64) were associated with an increased risk for clinical psychosis incidence. Of the clinical psychosis incidence in the population, 85.5% (95% CI: 64.6‐94.1) was attributable to prior psychopathology, with mood disorders (PAF=66.2, 95% CI: 33.4‐82.9), psychosis high‐risk state (PAF=36.9, 95% CI: 11.3‐55.1), and drug use disorders (PAF=18.7, 95% CI: –0.9 to 34.6) as the most important factors. Although the psychosis high‐risk state displayed a high relative risk for clinical psychosis outcome even after adjusting for other psychopathology, the PAF was comparatively low, given the low prevalence of psychosis high‐risk states in the population. These findings provide empirical evidence for the “prevention paradox” of targeted CHR early intervention. A comprehensive prevention strategy with a focus on broader psychopathology may be more effective than the current psychosis‐focused approach for achieving population‐based improvements in prevention of psychotic disorders.

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum

“…For the case-control analyses, as utilised in previous studies (Guloksuz et al ., 2019; Guloksuz et al ., 2020), ES-SCZ and PRS-SCZ were dichotomised at the quartile cut-off points based on the control distribution within each country (to account for differences between countries that may arise due to ethnic and geographical variation). The highest quartile was considered the binary risk state for schizophrenia (hereafter PRS-SCZ 75 and ES-SCZ 75 ).…”

“…weighted estimates of individual exposures from meta-analyses or simple summation of exposures. Recent studies indicate that the ES-SCZ is associated with psychosis risk states (Guloksuz et al ., 2020) as well as mental and physical health (Pries et al ., 2020b) in the general population.…”

Genetic liability in individuals at ultra-high risk of psychosis: A comparison study of 9 psychiatric traits

“…Previous studies have reported that the schizophrenia PRS identified and discriminated healthy individuals from individuals with first episode psychosis, schizophrenia and other psychoses [46][47][48][49][50]. More recently, Perkins et al (2020) [51] reported that the schizophrenia PRS discriminated psychosis converters from non-converters in an at-risk sample of European ancestry, while He et al (2019) [52] found no association between schizophrenia PRS and conversion to psychosis.…”

Dr. Strangelove, or how we learned to stop worrying and love uncertainty

“…Early psychopathology consists of a pluripotent mixed bag of phenotypic expressions that follow diverse trajectories defying traditional diagnoses. However, psychiatry has constructed balkanized frameworks modeled after traditional diagnostic silos, such as the clinical high-risk concept 4,5 . More recently, the transdiagnostic clinical staging model has been introduced to capture heterogeneity in clinical and functional outcomes, in order to improve prediction and prevention of illness progression 6 .…”

“…This situation is further exacerbated by the frequent co-occurrence of drug use disorders with other mental health conditions (dual disorders) 2 , a phenomenon associated with increases in emergency department admissions 3 and psychiatric hospitalizations 4 , higher risk of relapse to drug use 5 , and increased likelihood of premature deaths 6 , including those resulting from suicide 7 . The individual, social and public health impact of dual disorders is very high, and a multidisciplinary and comprehensive response to the needs of persons with these disorders is required.…”