Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-25T04:47:24.367Z Has data issue: false hasContentIssue false

Disentangling heterogeneity of psychosis expression in the general population: sex-specific moderation effects of environmental risk factors on symptom networks

Published online by Cambridge University Press:  25 August 2021

Linda T. Betz*
Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Nora Penzel
Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany
Marlene Rosen
Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Kamaldeep Bhui
Department of Psychiatry, University of Oxford, Oxford, UK Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
Rachel Upthegrove
Institute for Mental Health and Centre for Human Brain Health, University of Birmingham, Birmingham, UK Birmingham Early Intervention Service, Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Joseph Kambeitz
Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
Author for correspondence: Linda T. Betz, E-mail:



Psychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called ‘symptom network’. Differences in demographics, as well as exposure to adversities and risk factors, may produce substantial heterogeneity in symptom networks, highlighting potential etiological divergence in psychosis risk.


To explore this idea in a data-driven way, we employed a novel recursive partitioning approach in the 2007 English National Survey of Psychiatric Morbidity (N = 7242). We sought to identify ‘network phenotypes’ by explaining heterogeneity in symptom networks through potential moderators, including age, sex, ethnicity, deprivation, childhood abuse, separation from parents, bullying, domestic violence, cannabis use, and alcohol.


Sex was the primary source of heterogeneity in symptom networks. Additional heterogeneity was explained by interpersonal trauma (childhood abuse and domestic violence) in women and domestic violence, cannabis use, ethnicity in men. Among women, especially those exposed to early interpersonal trauma, an affective loading within psychosis may have distinct relevance. Men, particularly those from minority ethnic groups, demonstrated a strong network connection between hallucinatory experiences and persecutory ideation.


Symptom networks of psychosis expression in the general population are highly heterogeneous. The structure of symptom networks seems to reflect distinct sex-related adversities, etiologies, and mechanisms of symptom-expression. Disentangling the complex interplay of sex, minority ethnic group status, and other risk factors may help optimize early intervention and prevention strategies in psychosis.

Original Article
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


National Centre for Social Research, University of Leicester (2017). Adult psychiatric morbidity survey, 2007 (4th ed., Version 6379) [Data set]. UK Data Service. Scholar
Adams, J., Mrug, S., & Knight, D. C. (2018). Characteristics of child physical and sexual abuse as predictors of psychopathology. Child Abuse & Neglect, 86, 167177. ScholarPubMed
Barnow, S., Arens, E. A., Sieswerda, S., Dinu-Biringer, R., Spitzer, C., & Lang, S. (2010). Borderline personality disorder and psychosis: A review. Current Psychiatry Reports, 12(3), 186195. ScholarPubMed
Bebbington, P. (2015). Unravelling psychosis: Psychosocial epidemiology, mechanism, and meaning. Shanghai Archives of Psychiatry, 27(2), 70. ScholarPubMed
Bentall, R. P., Wickham, S., Shevlin, M., & Varese, F. (2012). Do specific early-life adversities lead to specific symptoms of psychosis? A study from the 2007 the adult psychiatric morbidity survey. Schizophrenia Bulletin, 38(4), 734740. ScholarPubMed
Berg, A. O., Andreassen, O. A., Aminoff, S. R., Romm, K. L., Hauff, E., & Melle, I. (2014). The impact of immigration and visible minority status on psychosis symptom profile. Social Psychiatry and Psychiatric Epidemiology, 49(11), 17471757. ScholarPubMed
Betz, L. T., Penzel, N., Kambeitz-Ilankovic, L., Rosen, M., Chisholm, K., Stainton, A., … PRONIA Consortium (2020). General psychopathology links burden of recent life events and psychotic symptoms in a network approach. npj Schizophrenia, 6(1), 40. Scholar
Binbay, T., Drukker, M., Elbi, H., Tanık, F. A., Özkınay, F., Onay, H., … Alptekin, K. (2012). Testing the psychosis continuum: Differential impact of genetic and nongenetic risk factors and comorbid psychopathology across the entire spectrum of psychosis. Schizophrenia Bulletin, 38(5), 9921002. ScholarPubMed
Bloomfield, M. A. P., Yusuf, F. N. I. B., Srinivasan, R., Kelleher, I., Bell, V., & Pitman, A. (2020). Trauma-informed care for adult survivors of developmental trauma with psychotic and dissociative symptoms: A systematic review of intervention studies. The Lancet Psychiatry, 7(5), 449462. ScholarPubMed
Davis, M. C., Matthews, K. A., & Twamley, E. W. (1999). Is life more difficult on Mars or Venus? A meta-analytic review of sex differences in major and minor life events. Annals of Behavioral Medicine, 21(1), 8397. ScholarPubMed
DeRosse, P., & Karlsgodt, K. H. (2015). Examining the psychosis continuum. Current Behavioral Neuroscience Reports, 2(2), 8089. ScholarPubMed
DeSantis, S. M., Baker, N. L., Back, S. E., Spratt, E., Ciolino, J. D., Moran-Santa Maria, M., … Brady, K. T. (2011). Gender differences in the effect of early life trauma on hypothalamic-pituitary-adrenal axis functioning. Depression and Anxiety, 28(5), 383392. ScholarPubMed
Dow-Edwards, D. (2020). Sex differences in the interactive effects of early life stress and the endocannabinoid system. Neurotoxicology and Teratology, 80, 106893. ScholarPubMed
Epskamp, S., Borsboom, D., & Fried, E. I. (2018). Estimating psychological networks and their accuracy: A tutorial paper. Behavior Research Methods, 50(1), 195212. ScholarPubMed
Epskamp, S., Cramer, A. O. J., Waldorp, L. J., Schmittmann, V. D., & Borsboom, D. (2012). qgraph: Network visualizations of relationships in psychometric data. Journal of Statistical Software, 48(4), 118. Scholar
Forbes, M. K., Wright, A. G. C., Markon, K. E., & Krueger, R. F. (2017). Evidence that psychopathology symptom networks have limited replicability. Journal of Abnormal Psychology, 126(7), 969988. ScholarPubMed
Freeman, D. (2007). Suspicious minds: The psychology of persecutory delusions. Clinical Psychology Review, 27(4), 425457. ScholarPubMed
Freeman, D., Brugha, T., Meltzer, H., Jenkins, R., Stahl, D., & Bebbington, P. (2010). Persecutory ideation and insomnia: Findings from the second British national survey of psychiatric morbidity. Journal of Psychiatric Research, 44(15), 10211026. ScholarPubMed
Freeman, D., Sheaves, B., Goodwin, G. M., Yu, L.-M., Nickless, A., Harrison, P. J., … Espie, C. A. (2017). The effects of improving sleep on mental health (OASIS): A randomised controlled trial with mediation analysis. The Lancet. Psychiatry, 4(10), 749758. ScholarPubMed
Fried, E. I., Eidhof, M. B., Palic, S., Costantini, G., Huisman-van Dijk, H. M., Bockting, C. L. H., … Karstoft, K.-I. (2018). Replicability and generalizability of posttraumatic stress disorder (PTSD) networks: A cross-cultural multisite study of PTSD symptoms in four trauma patient samples. Clinical Psychological Science, 6(3), 335351. ScholarPubMed
Garety, P. A., Kuipers, E., Fowler, D., Freeman, D., & Bebbington, P. E. (2001). A cognitive model of the positive symptoms of psychosis. Psychological Medicine, 31(2), 189195. ScholarPubMed
Gold, S. N., Elhai, J. D., Lucenko, B. A., Swingle, J. M., & Hughes, D. M. (1998). Abuse characteristics among childhood sexual abuse survivors in therapy: A gender comparison. Child Abuse & Neglect, 22(10), 10051012. ScholarPubMed
Guloksuz, S., van Nierop, M., Bak, M., de Graaf, R., Ten Have, M., van Dorsselaer, S., … van Os, J. (2016). Exposure to environmental factors increases connectivity between symptom domains in the psychopathology network. BMC Psychiatry, 16, 223. ScholarPubMed
Guloksuz, S., van Nierop, M., Lieb, R., van Winkel, R., Wittchen, H.-U., & van Os, J. (2015). Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology. Psychological Medicine, 45(11), 23892401. ScholarPubMed
Hardy, A., O'Driscoll, C., Steel, C., van der Gaag, M., & van den Berg, D. (2020). A network analysis of post-traumatic stress and psychosis symptoms. Psychological Medicine, 18. ScholarPubMed
Hartung, C. M., & Lefler, E. K. (2019). Sex and gender in psychopathology: DSM-5 and beyond. Psychological Bulletin, 145(4), 390409. ScholarPubMed
Hawes, S. W., Trucco, E. M., Duperrouzel, J. C., Coxe, S., & Gonzalez, R. (2019). Developmental pathways of adolescent cannabis use: Risk factors, outcomes and sex-specific differences. Substance Use & Misuse, 54(2), 271281. ScholarPubMed
Hodes, G. E., & Epperson, C. N. (2019). Sex differences in vulnerability and resilience to stress across the life span. Biological Psychiatry, 86(6), 421432. ScholarPubMed
Hothorn, T., Hornik, K., van de Wiel, M., & Zeileis, A. (2008). Implementing a class of permutation tests: The coin package. Journal of Statistical Software, 28(8), 123. Scholar
Isvoranu, A.-M., Borsboom, D., van Os, J., & Guloksuz, S. (2016). A network approach to environmental impact in psychotic disorder: Brief theoretical framework. Schizophrenia Bulletin, 42(4), 870873. ScholarPubMed
Isvoranu, A.-M., Guloksuz, S., Epskamp, S., van Os, J., Borsboom, D., & GROUP Investigators (2019). Toward incorporating genetic risk scores into symptom networks of psychosis. Psychological Medicine, 50(4), 18. ScholarPubMed
Isvoranu, A.-M., van Borkulo, C. D., Boyette, L.-L., Wigman, J. T. W., Vinkers, C. H., Borsboom, D.Group Investigators (2017). A network approach to psychosis: Pathways between childhood trauma and psychotic symptoms. Schizophrenia Bulletin, 43(1), 187196. ScholarPubMed
Jones, P. J., Mair, P., Simon, T., & Zeileis, A. (2020). Network trees: A method for recursively partitioning covariance structures. Psychometrika, 85(4), 926945. Scholar
Kelleher, I., & Cannon, M. (2011). Psychotic-like experiences in the general population: Characterizing a high-risk group for psychosis. Psychological Medicine, 41(1), 16. Scholar
Kelleher, I., Keeley, H., Corcoran, P., Lynch, F., Fitzpatrick, C., Devlin, N., … Cannon, M. (2012). Clinicopathological significance of psychotic experiences in non-psychotic young people: Evidence from four population-based studies. The British Journal of Psychiatry: The Journal of Mental Science, 201(1), 2632. ScholarPubMed
Kendall-Tackett, K. A., Williams, L. M., & Finkelhor, D. (1993). Impact of sexual abuse on children: A review and synthesis of recent empirical studies. Psychological Bulletin, 113(1), 164180. ScholarPubMed
Lin, S.-Y., Fried, E. I., & Eaton, N. R. (2019). The association of life stress with substance use symptoms: A network analysis and replication. Journal of Abnormal Psychology, 129(2), 204214. ScholarPubMed
Linscott, R. J., & van Os, J. (2013). An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: On the pathway from proneness to persistence to dimensional expression across mental disorders. Psychological Medicine, 43(6), 11331149. ScholarPubMed
McManus, S., Meltzer, H., Brugha, T. S., Bebbington, P. E., & Jenkins, R. (2009). Adult psychiatric morbidity in England, 2007: Results of a household survey. Leeds: The NHS Information Centre for Health and Social Care. Scholar
McNally, R. J. (2021). Network analysis of psychopathology: Controversies and challenges. Annual Review of Clinical Psychology, 17, 3153. ScholarPubMed
Moffa, G., Catone, G., Kuipers, J., Kuipers, E., Freeman, D., Marwaha, S., … Bebbington, P. (2017). Using directed acyclic graphs in epidemiological research in psychosis: An analysis of the role of bullying in psychosis. Schizophrenia Bulletin, 43(6), 12731279. ScholarPubMed
Morgan, C., Fearon, P., Lappin, J., Heslin, M., Donoghue, K., Lomas, B., … Dazzan, P. (2017). Ethnicity and long-term course and outcome of psychotic disorders in a UK sample: The ÆSOP-10 study. The British Journal of Psychiatry: The Journal of Mental Science, 211(2), 8894. Scholar
Moriarity, D. P., van Borkulo, C., & Alloy, L. B. (2020). Inflammatory phenotype of depression symptom structure: A network perspective. Brain, Behavior, and Immunity, 93, 3542. ScholarPubMed
Murphy, J., McBride, O., Fried, E., & Shevlin, M. (2018). Distress, impairment and the extended psychosis phenotype: A network analysis of psychotic experiences in an US general population sample. Schizophrenia Bulletin, 44(4), 768777. Scholar
Myin-Germeys, I., & van Os, J. (2007). Stress-reactivity in psychosis: Evidence for an affective pathway to psychosis. Clinical Psychology Review, 27(4), 409424. ScholarPubMed
Popovic, D., Ruef, A., Dwyer, D. B., Antonucci, L. A., Eder, J., Sanfelici, R., … PRONIA Consortium (2020). Traces of trauma: A multivariate pattern analysis of childhood trauma, brain structure, and clinical phenotypes. Biological Psychiatry, 88(11), 829842. ScholarPubMed
Riecher-Rössler, A., Butler, S., & Kulkarni, J. (2018). Sex and gender differences in schizophrenic psychoses-a critical review. Archives of Women's Mental Health, 21(6), 627648. ScholarPubMed
Robinaugh, D. J., Hoekstra, R. H. A., Toner, E. R., & Borsboom, D. (2020). The network approach to psychopathology: A review of the literature 2008–2018 and an agenda for future research. Psychological Medicine, 50(3), 353366. Scholar
Rosen, M., Haidl, T. K., Ruhrmann, S., Vogeley, K., & Schultze-Lutter, F. (2019). Sex differences in symptomatology of psychosis-risk patients and in prediction of psychosis. Archives of Women's Mental Health, 23, 339349. ScholarPubMed
Russell, J. D., Keding, T. J., He, Q., Li, J. J., & Herringa, R. J. (2020). Childhood exposure to interpersonal violence is associated with greater transdiagnostic integration of psychiatric symptoms. Psychological Medicine, 19. ScholarPubMed
Singh, S. P., Brown, L., Winsper, C., Gajwani, R., Islam, Z., Jasani, R., … Birchwood, M. (2015). Ethnicity and pathways to care during first episode psychosis: The role of cultural illness attributions. BMC Psychiatry, 15, 287. ScholarPubMed
Singleton, N., Bumpstead, R., O'Brien, M., Lee, A., & Meltzer, H. (2003). Psychiatric morbidity among adults living in private households, 2000. International Review of Psychiatry, 15(1–2), 6573. ScholarPubMed
Smeets, F., Lataster, T., Dominguez, M.-D.-G., Hommes, J., Lieb, R., Wittchen, H.-U., & van Os, J. (2012). Evidence that onset of psychosis in the population reflects early hallucinatory experiences that through environmental risks and affective dysregulation become complicated by delusions. Schizophrenia Bulletin, 38(3), 531542. ScholarPubMed
Smeets, F., Lataster, T., Viechtbauer, W., Delespaul, P., & G.R.O.U.P. (2014). Evidence that environmental and genetic risks for psychotic disorder may operate by impacting on connections between core symptoms of perceptual alteration and delusional ideation. Schizophrenia Bulletin, 41(3), 687697. ScholarPubMed
Stainton, A., Chisholm, K., Woodall, T., Hallett, D., Reniers, R. L. E. P., Lin, A., & Wood, S. J. (2021). Gender differences in the experience of psychotic-like experiences and their associated factors: A study of adolescents from the general population. Schizophrenia Research, 228, 410416. ScholarPubMed
Strobl, C., Malley, J., & Tutz, G. (2009). An introduction to recursive partitioning: Rationale, application, and characteristics of classification and regression trees, bagging, and random forests. Psychological Methods, 14(4), 323348. ScholarPubMed
Thompson, M. P., Kingree, J. B., & Desai, S. (2004). Gender differences in long-term health consequences of physical abuse of children: Data from a nationally representative survey. American Journal of Public Health, 94(4), 599604. ScholarPubMed
Tolin, D. F., & Foa, E. B. (2002). Gender and PTSD: A cognitive model. In Kimerling, R. (Ed.), Gender and PTSD (Vol. 460, pp. 7697). New York, NY, USA: The Guilford Press. Retrieved from Scholar
Upthegrove, R., Chard, C., Jones, L., Gordon-Smith, K., Forty, L., Jones, I., & Craddock, N. (2015). Adverse childhood events and psychosis in bipolar affective disorder. The British Journal of Psychiatry: The Journal of Mental Science, 206(3), 191197. ScholarPubMed
Upthegrove, R., Lalousis, P., Mallikarjun, P., Chisholm, K., Griffiths, S. L., Iqbal, M., … PRONIA Consortium (2020). The psychopathology and neuroanatomical markers of depression in early psychosis. Schizophrenia Bulletin, 47(1), 249258. Scholar
Upthegrove, R., Marwaha, S., & Birchwood, M. (2017). Depression and schizophrenia: Cause, consequence, or trans-diagnostic issue? Schizophrenia Bulletin, 43(2), 240244. ScholarPubMed
Vanheusden, K., Mulder, C. L., van der Ende, J., Selten, J.-P., van Lenthe, F. J., Verhulst, F. C., & Mackenbach, J. P. (2008). Associations between ethnicity and self-reported hallucinations in a population sample of young adults in The Netherlands. Psychological Medicine, 38(8), 10951102. Scholar
van Nierop, M., Lecei, A., Myin-Germeys, I., Collip, D., Viechtbauer, W., Jacobs, N., … van Winkel, R. (2018). Stress reactivity links childhood trauma exposure to an admixture of depressive, anxiety, and psychosis symptoms. Psychiatry Research, 260, 451457. Scholar
van Nierop, M., Viechtbauer, W., Gunther, N., van Zelst, C., de Graaf, R., Ten Have, M., … van Winkel, R. (2015). Childhood trauma is associated with a specific admixture of affective, anxiety, and psychosis symptoms cutting across traditional diagnostic boundaries. Psychological Medicine, 45(6), 12771288. ScholarPubMed
van Os, J., & Reininghaus, U. (2016). Psychosis as a transdiagnostic and extended phenotype in the general population. World Psychiatry, 15(2), 118124. ScholarPubMed
Wagner, F. A., & Anthony, J. C. (2007). Male-female differences in the risk of progression from first use to dependence upon cannabis, cocaine, and alcohol. Drug and Alcohol Dependence, 86(2–3), 191198. ScholarPubMed
Williams, D. R. (2021). Bayesian estimation for Gaussian graphical models: Structure learning, predictability, and network comparisons. Multivariate Behavioral Research, 56(2), 117. ScholarPubMed
Williams, D. R., & Mulder, J. (2019). BGGM: A R package for Bayesian Gaussian Graphical Models. Preprint. Retrieved from Scholar
Williams, D. R., Rast, P., Pericchi, L. R., & Mulder, J. (2020). Comparing Gaussian graphical models with the posterior predictive distribution and Bayesian model selection. Psychological Methods, 25(5), 653672. ScholarPubMed
Wüsten, C., Schlier, B., Jaya, E. S., Genetic Risk and Outcome of Psychosis (GROUP) Investigators, Fonseca-Pedrero, E., Peters, E., … Lincoln, T. M. (2018). Psychotic experiences and related distress: A cross-national comparison and network analysis based on 7141 participants from 13 countries. Schizophrenia Bulletin, 44(6), 11851194. ScholarPubMed
Zeileis, A., Hothorn, T., & Hornik, K. (2008). Model-based recursive partitioning. Journal of Computational and Graphical Statistics, 17(2), 492514. Scholar
Supplementary material: File

Betz et al. supplementary material

Betz et al. supplementary material

Download Betz et al. supplementary material(File)
File 5.4 MB