Negative Prognostic Effect of Baseline Antipsychotic Exposure in Clinical High Risk for Psychosis (CHR-P): Is Pre-Test Risk Enrichment the Hidden Culprit?

INTRODUCTION: Sample enrichment is a key factor in contemporary early-detection strategies aimed at the identification of help-seekers at increased risk of imminent transition to psychosis. We undertook a meta-analytic investigation to ascertain the role of sample enrichment in the recently highlighted negative prognostic effect of baseline antipsychotic (AP) exposure in clinical high-risk (CHR-P) of psychosis individuals. METHODS: Systematic review and meta-analysis of all published studies on CHR-P were identified according to a validated diagnostic procedure. The outcome was the proportion of transition to psychosis, which was calculated according to the Freeman‐Tukey double arcsine transformation. RESULTS: Thirty-three eligible studies were identified, including 16 samples with details on AP exposure at baseline and 17 samples with baseline AP exposure as exclusion criterion for enrollment. Those with baseline exposure to AP (n = 395) had higher transition rates (29.9%; 95% CI: 25.1%–34.8%) than those without baseline exposure to AP in the same study (n = 1289; 17.2%; 15.1%–19.4%) and those coming from samples that did not include people who were exposed to AP at baseline (n = 2073; 16.2%; 14.6%–17.8%; P < .05 in both the fixed-effects and the random-effects models). Heterogeneity within studies was substantial, with values above 75% in all comparisons. CONCLUSIONS: Sample enrichment is not a plausible explanation for the higher risk of transition to psychosis of CHR-P individuals who were already exposed to AP at the enrollment in specialized early-detection programs. Baseline exposure to AP at CHR-P assessment is a major index of enhanced, imminent risk of psychosis

The Silent Side of the Spectrum: Schizotypy and the Schizotaxic Self

The identification of individuals carrying unexpressed genetic liability to schizophrenia is crucial for both etiological research and clinical risk stratification. Subclinical psychopathological features detectable in the nonpsychotic part of the schizophrenia spectrum could improve the delineation of informative vulnerability phenotypes. Inspired by Meehl's schizotaxia-schizotypy heuristic model, we tested anomalous subjective experiences (self-disorders, SDs) as a candidate vulnerability phenotype in a sample of nonpsychotic, genetically high-risk subjects. A total of 218 unaffected members of 6 extended multiplex families (assessed between 1989 and 1999 during the Copenhagen Schizophrenia Linkage Study) were stratified into 4 groups of increasing psychopathological expressivity: no mental illness (NMI), no mental illness with schizotypal traits (NMI-ST), personality disorders not fulfilling other personality disorders (OPDs), and schizotypal personality disorder (SPD). We tested the distribution of SDs among the subgroups, the effect of SDs on the risk of belonging to the different subgroups, and the effect of experimental grouping and concomitant psychopathology (ie, negative symptoms (NSs) and subpsychotic formal thought disorder [FTD]) on the chances of experiencing SDs. SDs distribution followed an incremental pattern from NMI to SPD. SDs were associated with a markedly increased risk of NMI-ST, OPDs, or SPD. The odds of SDs increased as a function of the diagnostic category assignment, independently of sociodemographics and concomitant subclinical psychopathology (NSs and FTD). The results support SDs as an expression of schizotaxic vulnerability and indicate a multidimensional model of schizotypy—characterized by SDs, NSs, FTD—as a promising heuristic construct to address liability phenotypes in genetically high-risk studies