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

Published online by Cambridge University Press:  04 October 2018

Rajiv Radhakrishnan ,
Sinan Guloksuz ,
Margreet ten Have ,
Ron de Graaf ,
Saskia van Dorsselaer ,
Nicole Gunther ,
Christian Rauschenberg ,
Ulrich Reininghaus ,
Lotta-Katrin Pries  and
Maarten Bak
...Show all authors
Rajiv Radhakrishnan
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
Sinan Guloksuz
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
Margreet ten Have
Affiliation:
Department of Epidemiology, Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands
Ron de Graaf
Affiliation:
Department of Epidemiology, Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands
Saskia van Dorsselaer
Affiliation:
Department of Epidemiology, Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands
Nicole Gunther
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands School of Psychology, Open University, Heerlen, The Netherlands
Christian Rauschenberg
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
Ulrich Reininghaus
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands Health Service and Population Research Department, Centre for Epidemiology and Public Health, Institute of Psychiatry, Psychology & Neuroscience, King's College, London, UK
Lotta-Katrin Pries
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
Maarten Bak
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands
Jim van Os*
Affiliation:
Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, the Netherlands Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands Department of Psychosis Studies, King's College London, King's Health Partners, Institute of Psychiatry, London, UK
*
Author for correspondence: Jim van Os, E-mail: [email protected]
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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.

Keywords

Affective dysregulationcannabischildhood adversityfamilial riskpopulation surveypsychosesrisk factorsurbanicity
Type
Original Articles
Information
Psychological Medicine , Volume 49 , Issue 11 , August 2019 , pp. 1879 - 1889
Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

These authors contributed as joint first authors.

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