The relationship between sex and functional outcome in first-episode schizophrenia: the role of premorbid adjustment and insight

Joseph Ventura, Kenneth L. Subotnik, Sam Han, Gerhard S. Hellemann, Michael F. Green, Keith H. Nuechterlein

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1 Scopus citations


Background Studies that examined sex differences in first-episode patients consistently show that males compared to females have poor premorbid adjustment, earlier age of onset, worse clinical characteristics, and poorer outcomes. However, little is known about potential mediators that could explain these sex differences. Methods Our sample consisted of 137 individuals with first episode schizophrenia (males, n = 105; 77%) with a mean age of 22.1(s.d. = 4.1) years and mean education of 12.5(s.d. = 1.7) years. At entry, patients were within 2 years of their first psychotic episode onset. Baseline assessments were conducted for premorbid adjustment, symptoms, cognitive functioning, insight, and at 6-months for role and social functioning. Results Males as compared to females had poorer premorbid adjustment across several key developmental periods (p < 0.01), an earlier age of onset [M = 20.3(3.3) v. 22.8(5.6), p = 0.002], more negative symptoms (p = 0.044), poorer insight (p = 0.031), and poorer baseline and 6-month role (p = 0.002) and social functioning (p = 0.034). Several of these variables in which males showed impairment were significant predictors of 6-month role and social functioning. Premorbid adjustment and insight mediated the relationship between sex and role and social functioning at 6-months, but not negative symptoms. Discussion Males compared to females were at lower levels across several key premorbid and clinical domains which are strongly associated with functional outcome supporting the hypothesis that males might have a more disabling form of schizophrenia. The relationship between sex with role and social functioning was mediated through premorbid adjustment and insight suggesting pathways for understanding why females might have a less disabling form of schizophrenia.

Original languageEnglish
Pages (from-to)6878-6887
Number of pages10
JournalPsychological Medicine
Issue number14
StatePublished - 14 Oct 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s), 2023.


  • Age of onset
  • first episode schizophrenia
  • functional outcome
  • insight
  • mediation analysis
  • neurocognition
  • premorbid adjustment
  • sex differences


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