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A population-based study of the risk of schizophrenia and bipolar disorder associated with parent–child separation during development

Published online by Cambridge University Press:  08 May 2015

D. Paksarian*
Affiliation:
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA National Institute of Mental Health, Bethesda, MD, USA
W. W. Eaton
Affiliation:
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
P. B. Mortensen
Affiliation:
The National Center For Register-Based Research, Aarhus, Denmark Center for Integrated Register-Based Research at Aarhus University (CIRRAU), Aarhus, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark
K. R. Merikangas
Affiliation:
National Institute of Mental Health, Bethesda, MD, USA
C. B. Pedersen
Affiliation:
The National Center For Register-Based Research, Aarhus, Denmark Center for Integrated Register-Based Research at Aarhus University (CIRRAU), Aarhus, Denmark The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus and Copenhagen, Denmark
*
*Address for correspondence: D. Paksarian, Ph.D., Genetic Epidemiology Research Branch, National Institute of Mental Health, 35A Convent Drive, MSC3720, Bethesda, MD 20892, USA. (Email: diana.paksarian@nih.gov)

Abstract

Background

There is growing interest in the role of childhood adversities, including parental death and separation, in the etiology of psychotic disorders. However, few studies have used prospectively collected data to specifically investigate parental separation across development, or assessed the importance of duration of separation, and family characteristics.

Method

We measured three types of separation not due to death: maternal, paternal, and from both parents, across the ages of 1–15 years among a cohort of 985 058 individuals born in Denmark 1971–1991 and followed to 2011. Associations with narrowly and broadly defined schizophrenia and bipolar disorder in the psychiatric register were assessed in terms of separation occurrence, age of separation, and number of years separated. Interactions with parental history of mental disorder were assessed.

Results

Each type of separation was associated with all three outcomes, adjusting for age, sex, birth period, calendar year, family history of mental disorder, urbanicity at birth and parental age. Number of years of paternal separation was positively associated with both schizophrenia and bipolar disorder. Associations between separation from both parents and schizophrenia were stronger when separation occurred at later ages, while those with bipolar disorder remained stable across development. The first occurrence of paternal separation appeared to increase risk more when it occurred earlier in childhood. Associations differed according to parental history of mental disorder, although in no situation was separation protective.

Conclusions

Effects of parental separation may differ by type, developmental timing and family characteristics. These findings highlight the importance of considering such factors in studies of childhood adversity.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2015 

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References

Agid, O, Shapira, B, Zislin, J, Ritsner, M, Hanin, B, Murad, H, Troudart, T, Bloch, M, Heresco-Levy, U, Lerer, B (1999). Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Molecular Psychiatry 4, 163172.CrossRefGoogle ScholarPubMed
Andersen, SL (2003). Trajectories of brain development: point of vulnerability or window of opportunity? Neuroscience and Biobehavioral Reviews 27, 318.CrossRefGoogle ScholarPubMed
Anglin, DM, Cohen, PR, Chen, H (2008). Duration of early maternal separation and prediction of schizotypal symptoms from early adolescence to midlife. Schizophrenia Research 103, 143150.Google Scholar
Bentall, RP, Fernyhough, C (2008). Social predictors of psychotic experiences: specificity and psychological mechanisms. Schizophrenia Bulletin 34, 10121020.Google Scholar
Blakemore, SJ, Choudhury, S (2006). Development of the adolescent brain: implications for executive function and social cognition. Journal of Child Psychology and Psychiatry 47, 296312.Google Scholar
Bloch, M, Peleg, I, Koren, D, Aner, H, Klein, E (2007). Long-term effects of early parental loss due to divorce on the HPA axis. Hormones and Behavior 51, 516523.Google Scholar
Breslow, NE (1996). Generalized linear models: checking assumptions and strengthening conclusions. Statistica Applicata 8, 2341.Google Scholar
Canetti, L, Bachar, E, Bonne, O, Agid, O, Lerer, B, De-Nour, AK, Shalev, AY (2000). The impact of parental death versus separation from parents on the mental health of Israeli adolescents. Comprehensive Psychiatry 41, 360368.Google Scholar
Cantor-Graae, E, Pedersen, CB (2013). Full spectrum of psychiatric disorders related to foreign migration: a Danish population-based cohort study. JAMA Psychiatry 70, 427435.CrossRefGoogle ScholarPubMed
Clarke, MC, Tanskanen, A, Huttunen, MO, Cannon, M (2013). Sudden death of father or sibling in early childhood increases risk for psychotic disorder. Schizophrenia Research 143, 363366.CrossRefGoogle ScholarPubMed
Crook, T, Eliot, J (1980). Parental death during childhood and adult depression: a critical review of the literature. Psychological Bulletin 87, 252.Google Scholar
Daban, C, Vieta, E, Mackin, P, Young, A (2005). Hypothalamic–pituitary–adrenal axis and bipolar disorder. Psychiatric Clinics of North America 28, 469480.CrossRefGoogle ScholarPubMed
Erlenmeyer-Kimling, L, Rock, D, Squires-Wheeler, E, Roberts, S, Yang, J (1991). Early life precursors of psychiatric outcomes in adulthood in subjects at risk for schizophrenia or affective disorders. Psychiatry Research 39, 239256.CrossRefGoogle ScholarPubMed
Etain, B, Henry, C, Bellivier, F, Mathieu, F, Leboyer, M (2008). Beyond genetics: childhood affective trauma in bipolar disorder. Bipolar Disorders 10, 867876.Google Scholar
Feinberg, I (1983). Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? Journal of Psychiatric Research 17, 319334.Google Scholar
Fisher, HL, Jones, PB, Fearon, P, Craig, TK, Dazzan, P, Morgan, K, Hutchinson, G, Doody, GA, McGuffin, P, Leff, J (2010). The varying impact of type, timing and frequency of exposure to childhood adversity on its association with adult psychotic disorder. Psychological Medicine 40, 19671978.Google Scholar
Freedman, D, Brown, AS (2011). The developmental course of executive functioning in schizophrenia. International Journal of Developmental Neuroscience 29, 237243.CrossRefGoogle ScholarPubMed
Furukawa, T, Mizukawa, R, Hirai, T, Fujihara, S, Kitamura, T, Takahashi, K (1998). Childhood parental loss and schizophrenia: evidence against pathogenic but for some pathoplastic effects. Psychiatry Research 81, 353362.Google Scholar
Furukawa, TA, Ogura, A, Hirai, T, Fujihara, S, Kitamura, T, Takahashi, K (1999). Early parental separation experiences among patients with bipolar disorder and major depression: a case–control study. Journal of Affective Disorders 52, 8591.CrossRefGoogle ScholarPubMed
Harris, T, Brown, GW, Bifulco, A (1986). Loss of parent in childhood and adult psychiatric disorder: the role of lack of adequate parental care. Psychological Medicine 16, 641659.Google Scholar
Horesh, N, Apter, A, Zalsman, G (2011). Timing, quantity and quality of stressful life events in childhood and preceding the first episode of bipolar disorder. Journal of Affective Disorders 134, 434437.Google Scholar
Jakobsen, KD, Frederiksen, JN, Hansen, T, Jansson, LB, Parnas, J, Werge, T (2005). Reliability of clinical ICD-10 schizophrenia diagnoses. Nordic Journal of Psychiatry 59, 209212.CrossRefGoogle ScholarPubMed
Kaplow, JB, Widom, CS (2007). Age of onset of child maltreatment predicts long-term mental health outcomes. Journal of Abnormal Psychology 116, 176187.CrossRefGoogle ScholarPubMed
Kendler, KS, Neale, MC, Kessler, RC, Heath, AC, Eaves, LJ (1992). Childhood parental loss and adult psychopathology in women: a twin study perspective. Archives of General Psychiatry 49, 109116.CrossRefGoogle ScholarPubMed
Kendler, KS, Neale, MC, Prescott, CA, Kessler, RC, Heath, AC, Corey, LA, Eaves, LJ (1996). Childhood parental loss and alcoholism in women: a causal analysis using a twin-family design. Psychological Medicine 26, 7995.Google Scholar
Kendler, KS, Sheth, K, Gardner, CO, Prescott, CA (2002). Childhood parental loss and risk for first-onset of major depression and alcohol dependence: the time-decay of risk and sex differences. Psychological Medicine 32, 11871194.CrossRefGoogle ScholarPubMed
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, Lepine, JP, Ormel, J, Posada-Villa, J, Sagar, R, Tsang, A, Ustun, 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, 378385.CrossRefGoogle ScholarPubMed
Kumari, M, Head, J, Bartley, M, Stansfeld, S, Kivimaki, M (2013). Maternal separation in childhood and diurnal cortisol patterns in mid-life: findings from the Whitehall II study. Psychological Medicine 43, 633643.CrossRefGoogle ScholarPubMed
Laird, N, Olivier, D (1981). Covariance analysis of censored survival data using log-linear analysis techniques. Journal of the American Statistical Association 76, 231240.Google Scholar
Laursen, TM, Munk-Olsen, T, Nordentoft, M, Mortensen, PB (2007). A comparison of selected risk factors for unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia from a Danish population-based cohort. Journal of Clinical Psychiatry 68, 16731681.Google Scholar
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience 10, 434445.CrossRefGoogle ScholarPubMed
Mallett, R, Leff, J, Bhugra, D, Pang, D, Zhao, JH (2002). Social environment, ethnicity and schizophrenia. A case–control study. Social Psychiatry and Psychiatric Epidemiology 37, 329335.Google Scholar
Marco, EM, Adriani, W, Llorente, R, Laviola, G, Viveros, M (2009). Detrimental psychophysiological effects of early maternal deprivation in adolescent and adult rodents: altered responses to cannabinoid exposure. Neuroscience and Biobehavioral Reviews 33, 498507.Google Scholar
Morgan, C, Fisher, H (2007). Environment and schizophrenia: environmental factors in schizophrenia: childhood trauma – a critical review. Schizophrenia Bulletin 33, 310.CrossRefGoogle ScholarPubMed
Morgan, C, Fisher, H, Hutchinson, G, Kirkbride, J, Craig, TK, Morgan, K, Dazzan, P, Boydell, J, Doody, GA, Jones, PB, Murray, RM, Leff, J, Fearon, P (2009). Ethnicity, social disadvantage and psychotic-like experiences in a healthy population based sample. Acta Psychiatrica Scandinavica 119, 226235.Google Scholar
Morgan, C, Kirkbridge, 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, 495503.Google Scholar
Morris, AS, Silk, JS, Steinberg, L, Myers, SS, Robinson, LR (2007). The role of the family context in the development of emotion regulation. Social Development 16, 361388.CrossRefGoogle ScholarPubMed
Mors, O, Perto, GP, Mortensen, PB (2011). The Danish psychiatric central research register. Scandinavian Journal of Public Health 39, 5457.CrossRefGoogle ScholarPubMed
Mortensen, PB, Pedersen, CB, Melbye, M, Mors, O, Ewald, H (2003). Individual and familial risk factors for bipolar affective disorders in Denmark. Archives of General Psychiatry 60, 12091215.Google Scholar
Mortensen, PB, Pedersen, CB, Westergaard, T, Wohlfahrt, J, Ewald, H, Mors, O, Andersen, PK, Melbye, M (1999). Effects of family history and place and season of birth on the risk of schizophrenia. New England Journal of Medicine 340, 603608.Google Scholar
Nicolson, NA (2004). Childhood parental loss and cortisol levels in adult men. Psychoneuroendocrinology 29, 10121018.Google Scholar
Nishi, M, Noriko, H, Sasagawa, T, Matsunaga, W (2012). Effects of early life stress on brain activity: implications from maternal separation model in rodents. General and Comparative Endocrinology 181, 306309.CrossRefGoogle ScholarPubMed
Nomura, Y, Wickramaratne, PJ, Warner, V, Mufson, L, Weissman, MM (2002). Family discord, parental depression, and psychopathology in offspring: ten-year follow-up. Journal of the American Academy of Child and Adolescent Psychiatry 41, 402409.CrossRefGoogle ScholarPubMed
Parker, KJ, Maestripieri, D (2011). Identifying key features of early stressful experiences that produce stress vulnerability and resilience in primates. Neuroscience and Biobehavioral Reviews 35, 14661483.Google Scholar
Paus, T (2005). Mapping brain maturation and cognitive development during adolescence. Trends in Cognitive Sciences 9, 6068.Google Scholar
Pedersen, CB, Gøtzsche, H, Møller, , Mortensen, PB (2006). The Danish civil registration system. Danish Medical Bulletin 53, 441449.Google ScholarPubMed
Penn, DL, Sanna, LJ, Roberts, DL (2008). Social cognition in schizophrenia: an overview. Schizophrenia Bulletin 34, 408411.CrossRefGoogle ScholarPubMed
Pert, L, Ferriter, M, Saul, C (2004). Parental loss before the age of 16 years: a comparative study of patients with personality disorder and patients with schizophrenia in a high secure hospital's population. Psychology and Psychotherapy: Theory, Research and Practice 77, 403407.CrossRefGoogle Scholar
Pesonen, AK, Räikkönen, K, Feldt, K, Heinonen, K, Osmond, C, Phillips, DI, Barker, DJ, Eriksson, JG, Kajantie, E (2010). Childhood separation experience predicts HPA axis hormonal responses in late adulthood: a natural experiment of World War II. Psychoneuroendocrinology 35, 758767.Google Scholar
Pfohl, B, Stangl, D, Tsuang, MT (1983). The association between early parental loss and diagnosis in the Iowa 500. Archives of General Psychiatry 40, 965.CrossRefGoogle ScholarPubMed
Phillips, LJ, McGorry, PD, Garner, B, Thompson, KN, Pantelis, C, Wood, SJ, Berger, G (2006). Stress, the hippocampus and the hypothalamic–pituitary–adrenal axis: implications for the development of psychotic disorders. Australian and New Zealand Journal of Psychiatry 40, 725741.CrossRefGoogle ScholarPubMed
Pilowsky, DJ, Wickramaratne, P, Nomura, Y, Weissman, MM (2006). Family discord, parental depression, and psychopathology in offspring: 20-year follow-up. Journal of the American Academy of Child and Adolescent Psychiatry 45, 452460.CrossRefGoogle ScholarPubMed
Räikkönen, K, Lahti, M, Heinonen, K, Pesonen, A-K, Wahlbeck, K, Kajantie, E, Osmond, C, Barker, DJP, Eriksson, JG (2011). Risk of severe mental disorders in adults separated temporarily from their parents in childhood: The Helsinki Birth Cohort Study. Journal of Psychiatric Research 45, 332338.CrossRefGoogle ScholarPubMed
Read, J, Os, J, Morrison, AP, Ross, CA (2005). Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatrica Scandinavica 112, 330350.Google Scholar
Rubino, IA, Nanni, RC, Pozzi, DM, Siracusano, A (2009). Early adverse experiences in schizophrenia and unipolar depression. Journal of Nervous and Mental Disease 197, 6568.Google Scholar
Rutter, M (1971). Parent–child separation: psychological effects on the children. Journal of Child Psychology and Psychiatry 12, 233260.CrossRefGoogle ScholarPubMed
Salas, M, Hotman, A, Stricker, BH (1999). Confounding by indication: an example of variation in the use of epidemiologic terminology. American Journal of Epidemiology 149, 981983.Google Scholar
SAS Institute (2008). SAS Statistical Software. SAS Institute: Cary, NC.Google Scholar
Scott, KM, Smith, DR, Ellis, PM (2010). Prospectively ascertained child maltreatment and its association with DSM-IV mental disorders in young adults. Archives of General Psychiatry 67, 712719.Google Scholar
Stilo, SA, Di Forti, M, Mondelli, V, Falcone, AM, Russo, M, O'Connor, J, Palmer, E, Paparelli, A, Kolliakou, A, Sirianni, M (2012). Social disadvantage: cause or consequence of impending psychosis? Schizophrenia Bulletin 39, 12881295.CrossRefGoogle ScholarPubMed
Susser, E, Widom, CS (2012). Still searching for lost truths about the bitter sorrows of childhood. Schizophrenia Bulletin 38, 672675.CrossRefGoogle ScholarPubMed
Tennant, C (1988). Parental loss in childhood: its effect in adult life. Archives of General Psychiatry 45, 10451050.Google Scholar
Tottenham, N, Sheridan, MA (2010). A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing. Frontiers in Human Neuroscience 8, 68.Google Scholar
Tsuchiya, KJ, Agerbo, E, Mortensen, PB (2005). Parental death and bipolar disorder: a robust association was found in early maternal suicide. Journal of Affective Disorders 86, 151159.Google Scholar
Tyrka, AR, Wier, L, Price, LH, Ross, N, Anderson, GM, Wilkinson, CW, Carpenter, LL (2008). Childhood parental loss and adult hypothalamic–pituitary–adrenal function. Biological Psychiatry 63, 11471154.Google Scholar
Ubbesen, MB, Petersen, L, Mortensen, PB, Kristensen, OS (2013). Temporal stability of entries and predictors for entry into out-of-home care before the third birthday: a Danish population-based study of entries from 1981 to 2008. Children and Youth Services Review 35, 15261535.CrossRefGoogle Scholar
Uggerby, P, Østergaard, SD, Røge, R, Correll, CU, Nielsen, J (2013). The validity of the schizophrenia diagnosis in the Danish Psychiatric Central Research Register is good. Danish Medical Journal 60, A4578A4578.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, 661671.Google Scholar
Walker, E, Mittal, V, Tessner, K (2008). Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia. Annual Review of Clinical Psychology 4, 189216.Google Scholar
Walker, EF, Cudeck, R, Mednick, SA, Schulsinger, F (1981). Effects of parental absence and institutionalization on the development of clinical symptoms in high-risk children. Acta Psychiatrica Scandinavica 63, 95109.Google Scholar
Werner, S, Malaspina, D, Rabinowitz, J (2007). Socioeconomic status at birth is associated with risk of schizophrenia: population-based multilevel study. Schizophrenia Bulletin 33, 13731378.CrossRefGoogle ScholarPubMed
Wicks, S, Hjern, A, Gunnell, D, Lewis, G, Dalman, C (2005). Social adversity in childhood and the risk of developing psychosis: a national cohort study. American Journal of Psychiatry 162, 16521657.CrossRefGoogle ScholarPubMed
Woodward, L, Fergusson, DM, Belsky, J (2000). Timing of parental separation and attachment to parents in adolescence: results of a prospective study from birth to age 16. Journal of Marriage and Family 62, 162174.Google Scholar
World Health Organization (1967). International Classification of Diseases, Eighth Revision (ICD-8) . World Health Organization: Geneva.Google Scholar
World Health Organization (1992). The ICD-10 Classification of Mental and Behavioral Disorders. Clinical Descriptions and Diagnostic Guidelines. World Health Organization: Geneva.Google Scholar
Zammit, S, Owen, MJ, Lewis, G (2010). Misconceptions about gene–environment interactions in psychiatry. Evidence-Based Mental Health 13, 6568.Google Scholar
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