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Clinical indicators of treatment-resistant psychosis.
- Source :
-
The British journal of psychiatry : the journal of mental science [Br J Psychiatry] 2020 May; Vol. 216 (5), pp. 259-266. - Publication Year :
- 2020
-
Abstract
- Background: Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.<br />Aims: To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).<br />Method: In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.<br />Results: Younger age at onset (odds ratio 0.94, P = 7.79 × 10-13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10-4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10-3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.<br />Conclusions: People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.
- Subjects :
- Adult
Aging
Antipsychotic Agents therapeutic use
DNA Copy Number Variations
Female
Genetic Predisposition to Disease
Humans
Intelligence Tests
Male
Maternal Age
Multifactorial Inheritance genetics
Odds Ratio
Social Adjustment
Treatment Outcome
Young Adult
Age of Onset
Drug Resistance genetics
Marijuana Smoking
Paternal Age
Psychotic Disorders drug therapy
Psychotic Disorders genetics
Schizophrenia drug therapy
Schizophrenia genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1472-1465
- Volume :
- 216
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The British journal of psychiatry : the journal of mental science
- Publication Type :
- Academic Journal
- Accession number :
- 31155017
- Full Text :
- https://doi.org/10.1192/bjp.2019.120