Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway


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Van Os J., Pries L., Ten Have M., De Graaf R., Van Dorsselaer S., Delespaul P., ...More

Psychological Medicine, vol.52, no.10, pp.1910-1922, 2022 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 52 Issue: 10
  • Publication Date: 2022
  • Doi Number: 10.1017/s0033291720003748
  • Journal Name: Psychological Medicine
  • Journal Indexes: Science Citation Index Expanded, Social Sciences Citation Index, Scopus, Academic Search Premier, ASSIA, IBZ Online, PASCAL, Abstracts in Social Gerontology, AgeLine, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Psycinfo, Public Affairs Index, Veterinary Science Database
  • Page Numbers: pp.1910-1922
  • Keywords: Affective pathway, childhood adversity, environment, genetics, psychosis, MENTAL-HEALTH SURVEY, SCHIZOPHRENIA SPECTRUM DISORDERS, 1ST EPISODE PSYCHOSIS, CHILDHOOD TRAUMA, PSYCHIATRIC-DISORDERS, CLINICAL PSYCHOSIS, GENERAL-POPULATION, NEGATIVE SYMPTOMS, NETWORK APPROACH, SHORT-FORM

Abstract

Copyright © The Author(s) 2020. Published by Cambridge University Press.Background There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation. Methods We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls. Results The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: -0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465). Conclusions The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.