Interaction between environmental and familial affective risk impacts psychosis admixture in states of affective dysregulation

Rajiv Radhakrishnan, Sinan Guloksuz, Margreet ten Have, Ron de Graaf, Saskia van Dorsselaer, Nicole Gunther, Christian Rauschenberg, Ulrich Reininghaus, Lotta-Katrin Pries, Maarten Bak, Jim van Os*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background Evidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming 'complicated' by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms. Methods Data were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was 'complicated' by low-grade psychotic experiences ('attenuated psychosis' - moderately severe) and, overt psychotic symptoms leading to help-seeking ('clinical psychosis' - most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history x environmental risk interaction. Results In proxy gene-environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation. Conclusion Known environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here.

Original languageEnglish
Pages (from-to)1879-1889
Number of pages11
JournalPsychological Medicine
Volume49
Issue number11
Early online date4 Oct 2018
DOIs
Publication statusPublished - Aug 2019

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Keywords

  • Affective dysregulation
  • cannabis
  • childhood adversity
  • familial risk
  • population survey
  • psychoses
  • risk factors
  • urbanicity
  • ANXIETY
  • NETWORK APPROACH
  • SCHIZOPHRENIA
  • STRESS-REACTIVITY
  • CHILDHOOD TRAUMA
  • MENTAL-HEALTH SURVEY
  • EXPERIENCES
  • AFFECTIVE PATHWAY
  • CANNABIS USE
  • DISORDER

Cite this

Radhakrishnan, R., Guloksuz, S., ten Have, M., de Graaf, R., van Dorsselaer, S., Gunther, N., Rauschenberg, C., Reininghaus, U., Pries, L-K., Bak, M., & van Os, J. (2019). Interaction between environmental and familial affective risk impacts psychosis admixture in states of affective dysregulation. Psychological Medicine, 49(11), 1879-1889. https://doi.org/10.1017/S0033291718002635