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

  • Rajiv Radhakrishnan (a1), Sinan Guloksuz (a1) (a2), Margreet ten Have (a3), Ron de Graaf (a3), Saskia van Dorsselaer (a3), Nicole Gunther (a2) (a4), Christian Rauschenberg (a2), Ulrich Reininghaus (a2) (a5), Lotta-Katrin Pries (a2), Maarten Bak (a2) and Jim van Os (a2) (a6) (a7)...
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 × 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.

Copyright
Corresponding author
Author for correspondence: Jim van Os, E-mail: vanosj@gmail.com
Footnotes
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These authors contributed as joint first authors.

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References
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Psychological Medicine
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