Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis

JAMA Psychiatry. 2019 Jan 1;76(1):61-70. doi: 10.1001/jamapsychiatry.2018.2552.


Importance: The clinical high-risk state in psychosis is most often characterized by subthreshold psychotic symptoms (STPS) and represents a target for psychosis prevention. However, evidence suggests that between 30% and 50% of patients with a first episode of psychosis (FEP) report no prior history of STPS, indicating that not all patients with FEP experience a previous clinical high-risk phase. As with other early characteristics of illness onset, this diversity in the early course of symptoms may offer prognostic value for subsequent clinical trajectories.

Objective: To determine whether a history of pre-onset STPS is associated with differential 1-year treatment outcomes in an early intervention service for FEP.

Design, setting, and participants: Data on 195 patients 15 to 35 years of age who were recruited between January 17, 2003, and October 17, 2013, were collected from a catchment-based specialized early intervention service for FEP. Patients who reported experiencing at least 1 STPS prior to the onset of FEP were identified as STPS present (STPSp; n = 135); those who reported no such history were identified as STPS absent (STPSa; n = 60). Statistical analysis was conducted from December 15, 2016, to February 15, 2018.

Main outcomes and measures: Summary scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Hamilton Anxiety Rating Scale, Global Assessment of Functioning scores, and Social and Occupational Functioning Assessment Scale scores at baseline and after 1 year of treatment were analyzed to evaluate 1-year outcomes.

Results: Individuals in the STPSp group (39 female and 96 male participants; mean [SD] age, 23.4 [4.2] years) and the STPSa group (20 female and 40 male participants; mean [SD] age, 23.9 [5.1] years) did not differ in symptom severity or functioning at baseline. Although both groups improved by 1 year of treatment, mixed analyses of covariance (controlling for duration of untreated psychosis) revealed group-by-time interactions for scores on the Scale for the Assessment of Negative Symptoms (F1,192 = 6.17; P = .01), the Global Assessment of Functioning (F1,188 = 7.54; P = .006), and the Social and Occupational Functioning Assessment Scale (F1,192 = 3.79; P = .05). Mixed analyses of covariance also revealed a group effect for scores on the Scale for the Assessment of Positive Symptoms (F1,192 = 5.31; P = .02). After controlling for multiple comparisons, all significant results indicate poorer 1-year outcomes for patients with STPSp compared with patients with STPSa.

Conclusions and relevance: A history of pre-onset STPS consistent with a prior clinical high-risk state is associated with poorer outcomes in psychotic symptoms and global functioning for patients after 1 year of treatment for FEP. The presence or absence of pre-onset STPS therefore has prognostic value for treatment outcomes, even during a later stage of psychotic illness.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use
  • Case-Control Studies
  • Early Medical Intervention / methods*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Prodromal Symptoms
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / diagnosis*
  • Psychotic Disorders / drug therapy
  • Young Adult


  • Antipsychotic Agents