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The impact of childhood adversity on the persistence of psychotic symptoms: a systematic review and meta-analysis

Published online by Cambridge University Press:  23 April 2015

A. Trotta ,
R. M. Murray  and
H. L. Fisher
A. Trotta*
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
R. M. Murray
Affiliation:
Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
H. L. Fisher
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
*
*Address for correspondence: Dr A. Trotta, PO52 Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, 16 De Crespigny Park, London SE5 8AF, UK. (Email: [email protected])
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Abstract

Background

Evidence suggests that childhood adversity is associated with the development of psychotic experiences (PE), psychotic symptoms and disorders. However, less is known regarding the impact of early adversity on the persistence of PE and clinically relevant psychosis. Thus we conducted a systematic review of the association between childhood adversity and the course of PE and symptoms over time.

Method

A systematic search of Medline, EMBASE and PsychINFO databases was undertaken to identify articles published between January 1956 and November 2014. We included studies conducted on general population samples, individuals at ultra-high risk (UHR) of psychosis, and patients with full-blown psychotic disorders. A meta-analysis was performed on a subgroup.

Results

A total of 20 studies were included. Of these, 17 reported positive associations between exposure to overall or specific subtypes of childhood adversity and persistence of PE or clinically relevant psychotic symptoms. A meta-analysis of nine studies yielded a weighted odds ratio of 1.76 [95% confidence interval (CI) 1.19–2.32, p < 0.001] for general population studies and 1.55 (95% CI 0.32–2.77, p = 0.007) for studies conducted using clinical populations.

Conclusions

The available evidence is limited but tentatively suggests that reported exposure to adverse events in childhood is associated with persistence of PE and clinically relevant psychotic symptoms. This partially strengthens the case for addressing the consequences of early adversity in individuals presenting with psychotic phenomena to improve long-term outcomes. However, the heterogeneity of studies was high which urges caution in interpreting the results and highlights the need for more methodologically robust studies.

Keywords

Adversitycoursemeta-analysispersistencepsychosispsychotic symptoms
Type
Review Article
Information
Psychological Medicine , Volume 45 , Issue 12 , September 2015 , pp. 2481 - 2498
Copyright
Copyright © Cambridge University Press 2015 

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References

Alvarez, MJ, Roura, P, Osés, A, Foguet, Q, Solà, J, Arrufat, FX (2011). Prevalence and clinical impact of childhood trauma in patients with severe mental disorders. Journal of Nervous and Mental Disease 199, 156–161.Google Scholar
Álvarez-Jiménez, M, Gleeson, JF, Henry, LP, Harrigan, SM, Harris, MG, Amminger, GP, Killackey, E, Yung, AR, Herrman, H, Jackson, HJ, McGorry, PD (2011). Prediction of a single psychotic episode: a 7.5-year, prospective study in first-episode psychosis. Schizophrenia Research 125, 236–246.Google Scholar
Arseneault, L, Cannon, M, Fisher, HL, Polanczyk, G, Moffitt, TE, Caspi, A (2011). Childhood trauma and children's emerging psychotic symptoms: a genetically sensitive longitudinal cohort study. American Journal of Psychiatry 168, 65–72.Google Scholar
Beards, S, Gayer-Anderson, C, Borges, S, Fisher, HL, Morgan, C (2013). Life events and psychosis: a review and meta-analysis. Schizophrenia Bulletin 39, 740–747.CrossRefGoogle ScholarPubMed
Bebbington, PE, Bhugra, D, Brugha, T, Singleton, N, Farrell, M, Jenkins, R, Lewis, G, Meltzer, H (2004). Psychosis, victimisation and childhood disadvantage: evidence from the second British National Survey of Psychiatric Morbidity. British Journal of Psychiatry 185, 220–226.CrossRefGoogle ScholarPubMed
Bechdolf, A, Thompson, A, Nelson, B, Cotton, S, Simmons, MB, Amminger, GP, Leicester, S, Francey, SM, McNab, C, Krstev, H, Sidis, A, McGorry, PD, Yung, AR (2010). Experience of trauma and conversion to psychosis in an ultra-high-risk (prodromal) group. Acta Psychiatrica Scandinavica 121, 377–384.Google Scholar
Bendall, S, Jackson, HJ, Hulbert, CA, McGorry, PD (2008). Childhood trauma and psychotic disorders: a systematic, critical review of the evidence. Schizophrenia Bulletin 34, 568–579.Google Scholar
Bentall, RP, de Sousa, P, Varese, F, Wickham, S, Sitko, K, Haarmans, M, Read, J (2014). From adversity to psychosis: pathways and mechanisms from specific adversities to specific symptoms. Social Psychiatry & Psychiatric Epidemiology 49, 1011–1022.Google Scholar
Brown, GW, Craig, TK, Harris, TO, Handley, RV, Harvey, AL (2007). Development of a retrospective interview measure of parental maltreatment using the Childhood Experience of Care and Abuse (CECA) instrument – A life-course study of adult chronic depression – 1. Journal of Affective Disorders, 103, 205–215.Google Scholar
Butchart, A, Putney, H, Furniss, T, Kahane, T (2006). Preventing child maltreatment: a guide to taking action and generating evidence. World Health Organisation: Geneva.Google Scholar
Cicchetti, D (1994). Editorial: advances and challenges in the study of the sequelae of child maltreatment. Developmental Psychopathology 6, 1–3.Google Scholar
Cohen, CI, Palekar, N, Barker, J, Ramirez, PM (2012). The relationship between trauma and clinical outcome variables among older adults with schizophrenia spectrum disorders. American Journal of Geriatric Psychiatry 20, 408–415.CrossRefGoogle ScholarPubMed
Collip, D, Myin-Germeys, I, van Os, J (2008). Does the concept of ‘sensitization’ provide a plausible mechanism for the putative link between the environment and schizophrenia? Schizophrenia Bulletin 34, 220–225.Google Scholar
Conus, P, Cotton, S, Schimmelmann, BG, McGorry, PD, Lambert, M (2010). Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients. Schizophrenia Bulletin 36, 1105–1114.CrossRefGoogle Scholar
Cougnard, A, Mercelis, M, Myin-Germeys, I, de Graaf, R, Vollebergh, WAM, Krabbendam, L, Lieb, R, Wittchen, HU, Henquet, C, Spauwen, J, van Os, J (2007). Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model. Psychological Medicine 37, 513–527.CrossRefGoogle ScholarPubMed
Davidson, G, Shannon, C, Mulholland, C, Campbell, J (2009). A longitudinal study of the effects of childhood trauma on symptoms and functioning of people with severe mental health problems. Journal of Trauma and Dissociation 10, 57–68.CrossRefGoogle ScholarPubMed
Dominguez, MD, Saka, MC, Lieb, R, Wittchen, HU, van Os, J (2010). Early expression of negative/disorganized symptoms predicting psychotic experiences and subsequent clinical psychosis: a 10-year study. American Journal of Psychiatry 167, 1075–1082.CrossRefGoogle Scholar
De Loore, E, Drukker, M, Gunther, N, Feron, F, Deboutte, D, Sabbe, B, Mengelers, R, van Os, J, Myin-Germeys, I (2007). Childhood negative experiences and subclinical psychosis in adolescence: a longitudinal general population study. Early Intervention in Psychiatry 1, 201–207.CrossRefGoogle Scholar
Der Simonian, R, Laird, N (1986). Meta-analysis in clinical trials. Controlled Clinical Trials 7, 177–188.Google Scholar
Egger, M, Davey Smith, G, Schneider, M, Minder, C (1997). Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 315, 629–634.Google Scholar
Escher, S, Romme, M, Buiks, A, Delespaul, P, van Os, J (2002). Formation of delusional ideation in adolescents hearing voices: a prospective study. American Journal of Medical Genetics 114, 913–920.Google Scholar
Fisher, HL, Craig, TK, Fearon, P, Morgan, K, Dazzan, P, Lappin, J, Hutchinson, G, Doody, GA, Jones, PB, McGuffin, P, Murray, RM, Leff, J, Morgan, C (2011). Reliability and comparability of psychosis patients’ retrospective reports of childhood abuse. Schizophrenia Bulletin 37, 546–553.Google Scholar
Fisher, HL, Jones, PB, Fearon, P, Craig, TK, Dazzan, P, Morgan, K, Hutchinson, G, Doody, GA, McGuffin, P, Leff, J, Murray, RM, Morgan, C (2010). The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder. Psychological Medicine 40, 1967–1978.CrossRefGoogle ScholarPubMed
Fisher, HL, Schreier, A, Zammit, S, Maughan, B, Munafò, MR, Lewis, G, Wolke, D (2013). Pathways between childhood victimization and psychosis-like symptoms in the ALSPAC birth cohort. Schizophrenia Bulletin 39, 1045–1055.CrossRefGoogle ScholarPubMed
Garety, PA, Bebbington, P, Fowler, D, Freeman, D, Kuipers, E (2007). Implications for neurobiological research of cognitive models of psychosis: a theoretical paper. Psychological Medicine, 37, 1377–1391.Google Scholar
Garno, JL, Goldberg, JF, Ramirez, PM, Ritzler, BA (2005). Impact of childhood abuse on the clinical course of bipolar disorder. British Journal of Psychiatry 186, 121–125.CrossRefGoogle ScholarPubMed
Gil, A, Gama, CS, de Jesus, DR, Lobato, MI, Zimmer, M, Belmonte-de-Abreu, P (2009). The association of child abuse and neglect with adult disability in schizophrenia and the prominent role of physical neglect. Child Abuse and Neglect 33, 618–624.CrossRefGoogle ScholarPubMed
Goff, DC, Brotman, AW, Kindlon, D, Waites, M, Amico, E (1991). Self-reports of childhood abuse in chronically psychotic patients. Psychiatry Research 37, 73–80.Google Scholar
Green, JG, Berglund, P, Gruber, MJ, McLaughlin, KA, Sampson, NA, Zaslavsky, AM, Kessler, RC (2010). Childhood adversities and adult psychopathology in the National Comorbidity Survey Replication (NCS-R). I: associations with first onset of DSM–IV disorders. Archives of General Psychiatry 67, 113–123.Google Scholar
Greenfield, SF, Strakowski, SM, Tohen, M, Batson, SC, Kolbrener, ML (1994). Childhood abuse in first-episode psychosis. British Journal of Psychiatry 164, 831–834.CrossRefGoogle ScholarPubMed
Heins, M, Simons, C, Lataster, T, Pfeifer, S, Versmissen, D, Lardinois, M, Marcelis, M, Delespaul, P, Krabbendam, L, van Os, J, Myin-Germeys, I (2011). Childhood trauma and psychosis: a case-control and case-sibling comparison across different levels of genetic liability, psychopathology, and type of trauma. American Journal of Psychiatry 168, 1286–1294.Google Scholar
Higgins, JPT, Thompson, SG, Deeks, JJ, Altman, DG (2003). Measuring inconsistency in meta-analyses. British Medical Journal 327, 557–560.Google Scholar
Howes, OD, Murray, RM (2014). Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 383, 1677–1687.CrossRefGoogle ScholarPubMed
Kelleher, I, Keeley, H, Corcoran, P, Ramsay, H, Wasserman, C, Carli, V, Sarchiapone, M, Hoven, C, Wasserman, D, Cannon, M (2013). Childhood trauma and psychosis in a prospective cohort study: cause, effect, and directionality. American Journal of Psychiatry 170, 734–741.CrossRefGoogle Scholar
Kessler, RC, McLaughlin, KA, Green, JG, Gruber, MJ, Sampson, NA, Zaslavsky, AM, Aguilar-Gaxiola, S, Alhamzawi, AO, Alonso, J, Angermeyer, M, Benjet, C, Bromet, E, Chatterji, S, de Girolamo, G, Demyttenaere, K, Fayyad, J, Florescu, S, Gal, G, Gureje, O, Haro, JM, Hu, CY, Karam, EG, Kawakami, N, Lee, S, Lépine, JP, Ormel, J, Posada-Villa, J, Sagar, R, Tsang, A, Ustün, TB, Vassilev, S, Viana, MC, Williams, DR (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. British Journal of Psychiatry 197, 378–385.Google Scholar
Kim, D, Kaspar, V, Noh, S, Nam, JH (2006). Sexual and physical abuse among Korean female inpatients with schizophrenia. Journal of Traumatic Stress 19, 279–289.CrossRefGoogle ScholarPubMed
Konings, M, Stefanis, N, Kuepper, R, de Graaf, R, ten Have, M, van Os, J, Bakoula, C, Henquet, C (2012). Replication in two independent population-based samples that childhood maltreatment and cannabis use synergistically impact on psychosis risk. Psychological Medicine 42, 149–159.Google Scholar
Lecomte, T, Spidel, A, Leclerc, C, MacEwan, GW, Greaves, C, Bentall, RP (2008). Predictors and profiles of treatment non-adherence and engagement in services problems in early psychosis. Schizophrenia Research 102, 295–302.Google Scholar
Linscott, RJ, 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, 1133–1149.Google Scholar
Lysaker, PH, Beattie, NL, Strasburger, AM, Davis, LW (2005). Reported history of child sexual abuse in schizophrenia: associations with heightened symptom levels and poorer participation over four months in vocational rehabilitation. Journal of Nervous and Mental Disease 193, 790–795.Google Scholar
Mackie, CJ, Castellanos-Ryan, N, Conrod, PJ (2011). Developmental trajectories of psychotic-like experiences across adolescence: impact of victimization and substance use. Psychological Medicine 41, 47–58.CrossRefGoogle ScholarPubMed
Manly, JT, Cicchetti, D, Barnett, D (1994). The impact of subtype, frequency, chronicity, and severity of child maltreatment on social competence and behaviour problems. Developmental Psychopatholology 6, 121–143.CrossRefGoogle Scholar
McCrory, E, De Brito, SA, Viding, E (2011). The impact of childhood maltreatment: a review of neurobiological and genetic factors. Frontiers in Psychiatry 2, 48.Google Scholar
Mondelli, V, Cattaneo, A, Belvederi Murri, M, Di Forti, M, Handley, R, Hepgul, N, Miorelli, A, Navari, S, Papadopoulos, AS, Aitchison, KJ, Morgan, C, Murray, RM, Dazzan, P, Pariante, CM (2011). Stress and inflammation reduce brain-derived neurotrophic factor expression in first episode psychosis: a pathway to smaller hippocampal volume. Journal of Clinical Psychiatry 72, 1677–1684.Google Scholar
Moher, D, Liberati, A, Tetzlaff, J, Altman, DG, The PRISMA Group (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. British Medical Journal 339, b2535.Google Scholar
Morgan, C, Fisher, H (2007). Environmental factors in schizophrenia: childhood trauma–a critical review. Schizophrenia Bulletin 33, 3–10.Google Scholar
Morgan, C, Kirkbride, J, Leff, J, Craig, T, Hutchinson, G, McKenzie, K, Morgan, K, Dazzan, P, Doody, GA, Jones, P, Murray, R, Fearon, P (2007). Parental separation, loss and psychosis in different ethnic groups: a case-control study. Psychological Medicine 37, 495–503.Google Scholar
Murphy, J, Houston, JE, Shevlin, M, Adamson, G (2013). Childhood sexual trauma, cannabis use and psychosis: statistically controlling for pre-trauma psychosis and psychopathology. Social Psychiatry and Psychiatric Epidemiology 48, 853–861.Google Scholar
Nanni, V, Uher, R, Danese, A (2012). Childhood maltreatment predicts unfavourable course of illness and treatment outcome in depression: a meta-analysis. American Journal of Psychiatry 169, 141–151.Google Scholar
Newman, JM, Turnbull, A, Berman, BA, Rodrigues, S, Serper, MR (2010). Impact of traumatic and violent victimization experiences in individuals with schizophrenia and schizoaffective disorder. Journal of Nervous and Mental Disease 198, 708–714.Google Scholar
Radford, L, Corral, S, Bradley, C, Fisher, H, Bassett, C, Howat, N, Collishaw, S (2011). Child Abuse and Neglect in the UK Today. NSPCC: London.Google Scholar
Read, J, van Os, J, Morrison, AP, Ross, CA (2005). Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica 112, 330–350.Google Scholar
Ross, CA, Anderson, G, Clark, P (1994). Childhood abuse and the positive symptoms of schizophrenia. Hospital & Community Psychiatry 45, 489–491.Google Scholar
Rössler, W, Hengartner, MP, Ajdacic-Gross, V, Haker, H, Angst, J (2014). Impact of childhood adversity on the onset and course of subclinical psychosis symptoms–results from a 30-year prospective community study. Schizophrenia Research 153, 189–195.Google Scholar
Schäfer, I, Fisher, HL (2011). Childhood trauma and psychosis – what is the evidence? Dialogues in Clinical Neuroscience 13, 360–365.Google Scholar
StataCorp (2009). Stata Statistical Software: Release 11. College Station, TX: StataCorp LP.Google Scholar
Spauwen, J, Krabbendam, L, Lieb, R, Wittchen, HU, van Os, J (2006). Impact of psychological trauma on the development of psychotic symptoms: relationship with psychosis proneness. British Journal of Psychiatry 188, 527–533.Google Scholar
Thapar, A, Heron, J, Jones, RB, Owen, MJ, Lewis, G, Zammit, S (2012). Trajectories of change in self-reported psychotic-like experiences in childhood and adolescence. Schizophrenia Research 140, 104–109.Google Scholar
Thompson, AD, Nelson, B, Yuen, HP, Lin, A, Amminger, GP, McGorry, PD, Wood, SJ, Yung, AR (2014). Sexual trauma increases the risk of developing psychosis in an ultra-high-risk ‘prodromal’ population. Schizophrenia Bulletin 40, 697–706.CrossRefGoogle Scholar
Trotta, A, Di Forti, M, Mondelli, V, Dazzan, P, Pariante, C, David, A, Mulè, A, Ferraro, L, Formica, I, Murray, RM, Fisher, HL (2013). Prevalence of bullying victimisation among first-episode psychosis patients and unaffected controls. Schizophrenia Research 150, 169–175.Google Scholar
Uçok, A, Bikmaz, S (2007). The effects of childhood trauma in patients with first-episode schizophrenia. Acta Psychiatrica Scandinavica 116, 371–377.Google Scholar
van Dam, DS, van Nierop, M, Viechtbauer, W, Velthorst, E, van Winkel, R, Genetic Risk and Outcome of Psychosis (GROUP) investigators, Bruggeman, R, Cahn, W, de Haan, L, Kahn, RS, Meijer, CJ, Myin-Germeys, I, van Os, J, Wiersma, D (2014). Childhood abuse and neglect in relation to the presence and persistence of psychotic and depressive symptomatology. Psychological Medicine 17, 1–15.Google Scholar
van Goozen, SHM, Fairchild, G (2008). How can the study of biological processes help design new interventions for children with severe antisocial behavior? Development and Psychopathology 20, 941–973.Google Scholar
van Nierop, M, Janssens, M, Genetic Risk OUtcome of Psychosis Investigators, Bruggeman, R, Cahn, W, de Haan, L, Kahn, RS, Meijer, CJ, Myin-Germeys, I, van Os, J, Wiersma, D (2013). Evidence that transition from health to psychotic disorder can be traced to semi-ubiquitous environmental effects operating against background genetic risk. PLoS ONE 8, e76690.Google Scholar
van Os, J (2014). The many continua of psychosis. JAMA Psychiatry 71, 985–986.Google Scholar
van Os, J, Linscott, RJ, Myin-Germeys, I, Delespaul, P, Krabbendam, L (2009). A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychological Medicine 39, 179–195.Google Scholar
van Winkel, R, Stefanis, NC, Myin-Germeys, I (2008). Psychosocial stress and psychosis. A review of the neurobiological mechanisms and the evidence for gene-stress interaction. Schizophrenia Bulletin 34, 1095–1105.Google Scholar
Varese, F, Smeets, F, Drukker, M, Lieverse, R, Lataster, T, Viechtbauer, W, Read, J, van Os, J, Bentall, RP (2012). Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies. Schizophrenia Bulletin 38, 661–671.Google Scholar
Verdoux, H, van Os, J, Maurice-Tison, S, Gay, B, Salamon, R, Bourgeois, ML (1999). Increased occurrence of depression in psychosis-prone subjects: a follow-up study in primary care settings. Comprehensive Psychiatry 40, 462–468.CrossRefGoogle ScholarPubMed
Vorontsova, N, Garety, P, Freeman, D (2013). Cognitive factors maintaining persecutory delusions in psychosis: the contribution of depression. Journal of Abnormal Psychology 122, 1121–1131.Google Scholar
Walker, E, Diforio, D (1997). Schizophrenia: a neural diathesis-stress model. Psychological Review 104, 667–685.Google Scholar
Wang, M, Bodner, TE (2007). Growth mixture modeling: identifying and predicting unobserved subpopulations with longitudinal data. Organizational Research Methods 10, 635–656.CrossRefGoogle Scholar
Wigman, JT, van Nierop, M, Vollebergh, WA, Lieb, R, Beesdo-Baum, K, Wittchen, HU, van Os, J (2012). Evidence that psychotic symptoms are prevalent in disorders of anxiety and depression, impacting on illness onset, risk, and severity: implications for diagnosis and ultra-high risk research. Schizophrenia Bulletin 38, 247–257.CrossRefGoogle ScholarPubMed
Wigman, JT, van Os, J, Abidi, L, Huibers, MJ, Roelofs, J, Arntz, A, Kelleher, I, Peeters, FP (2014). Subclinical psychotic experiences and bipolar spectrum features in depression: association with outcome of psychotherapy. Psychological Medicine 44, 325–336.Google Scholar
Wigman, JT, van Winkel, R, Jacobs, N, Wichers, M, Derom, C, Thiery, E, Vollebergh, WA, van Os, J (2011 a). A twin study of genetic and environmental determinants of abnormal persistence of psychotic experiences in young adulthood. American Journal of Medical Genetics Part B 156, 546–552.Google Scholar
Wigman, JT, van Winkel, R, Raaijmakers, QA, Ormel, J, Verhulst, FC, Reijneveld, SA, van Os, J, Vollebergh, WA (2011 b). Evidence for a persistent, environment-dependent and deteriorating subtype of subclinical psychotic experiences: a 6-year longitudinal general population study. Psychological Medicine 41, 2317–2329.Google Scholar
Willett, JB, Sayer, AG (1994). Using covariance structure analysis to detect correlates and predictors of individual change over time. Psychological Bulletin 116, 363–381.Google Scholar
Wolke, D, Lereya, ST, Fisher, HL, Lewis, G, Zammitt, S (2013). Bullying in elementary school and psychotic symptoms at 18 years: a longitudinal, population based cohort study. Psychological Medicine 17, 1–13.Google Scholar
Yung, AR, Phillips, LJ, Yuen, HP, McGorry, PD (2004). Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophrenia Research 67, 131–142.CrossRefGoogle Scholar
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