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Like father like daughter: sex-specific parent-of-origin effects in the transmission of liability for psychotic symptoms to offspring

Published online by Cambridge University Press:  29 August 2018

A. Aylott
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Nova Scotia Health Authority, Halifax, NS, Canada
A. Zwicker
Affiliation:
Department of Pathology, Dalhousie University, Halifax, NS, Canada
L. E. MacKenzie
Affiliation:
Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada
J. Cumby
Affiliation:
Nova Scotia Health Authority, Halifax, NS, Canada
L. Propper
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada IWK Health Centre, Halifax, NS, Canada
S. Abidi
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada IWK Health Centre, Halifax, NS, Canada
A. Bagnell
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada IWK Health Centre, Halifax, NS, Canada
H. L. Fisher
Affiliation:
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK
B. Pavlova
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Nova Scotia Health Authority, Halifax, NS, Canada
M. Alda
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Nova Scotia Health Authority, Halifax, NS, Canada
R. Uher*
Affiliation:
Department of Psychiatry, Dalhousie University, Halifax, NS, Canada Nova Scotia Health Authority, Halifax, NS, Canada Department of Pathology, Dalhousie University, Halifax, NS, Canada Department of Psychology and Neuroscience, Dalhousie University, Halifax, NS, Canada IWK Health Centre, Halifax, NS, Canada Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK
*
*Address for correspondence: Dr R. Uher, Dalhousie University, 5909 Veterans Memorial Lane, Halifax, NS, Canada B3H 2E2.E-mail: uher@dal.ca

Abstract

Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8–24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43–4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61–2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018 

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References

1. Dean, K, Stevens, H, Mortensen, PB, et al. Full spectrum of psychiatric outcomes among offspring with parental history of mental disorder. Arch Gen Psychiatry. 2010; 67, 822829.CrossRefGoogle ScholarPubMed
2. Rasic, D, Hajek, T, Alda, M, Uher, R. Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: a meta-analysis of family high-risk studies. Schizophr Bull. 2014; 40, 2838.CrossRefGoogle ScholarPubMed
3. Bevan, JR, Mars, B, Collishaw, S, et al. Prevalence and correlates of psychotic experiences amongst children of depressed parents. Psychiatry Res. 2016; 243, 8186.CrossRefGoogle Scholar
4. Polanczyk, G, Moffitt, TE, Arseneault, L, et al. Etiological and clinical features of childhood psychotic symptoms: results from a birth cohort. Arch Gen Psychiatry. 2010; 67, 328338.CrossRefGoogle ScholarPubMed
5. Zammit, S, Horwood, J, Thompson, A, et al. Investigating if psychosis-like symptoms (PLIKS) are associated with family history of schizophrenia or paternal age in the ALSPAC birth cohort. Schizophr Res. 2008; 104, 279286.CrossRefGoogle ScholarPubMed
6. Fisher, HL, Caspi, A, Poulton, R, et al. Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: a birth cohort study. Psychol Med. 2013; 43, 20772086.CrossRefGoogle ScholarPubMed
7. Poulton, R, Caspi, A, Moffitt, TE, et al. Children’s self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study. Arch Gen Psychiatry. 2000; 57, 10531058.CrossRefGoogle ScholarPubMed
8. Boks, MP, de Vette, MH, Sommer, IE, et al. Psychiatric morbidity and X-chromosomal origin in a Klinefelter sample. Schizophr Res. 2007; 93, 399402.CrossRefGoogle Scholar
9. DeLisi, LE, Maurizio, AM, Svetina, C, et al. Klinefelter’s syndrome (XXY) as a genetic model for psychotic disorders. Am J Med Genet B Neuropsychiatr Genet. 2005; 135B, 1523.CrossRefGoogle ScholarPubMed
10. Roser, P, Kawohl, W. Turner syndrome and schizophrenia: a further hint for the role of the X-chromosome in the pathogenesis of schizophrenic disorders. World J Biol Psychiatry. 2010; 11, 239242.CrossRefGoogle ScholarPubMed
11. Goldstein, JM, Cherkerzian, S, Tsuang, MT, Petryshen, TL. Sex differences in the genetic risk for schizophrenia: history of the evidence for sex-specific and sex-dependent effects. Am J Med Genet B Neuropsychiatr Genet. 2013; 162B, 698710.CrossRefGoogle ScholarPubMed
12. Editorial. Accounting for sex in the genome. Nat Med. 2017; 23, 1243.CrossRefGoogle Scholar
13. Wise, AL, Gyi, L, Manolio, TA. eXclusion: toward integrating the X chromosome in genome-wide association analyses. Am J Hum Genet. 2013; 92, 643647.CrossRefGoogle ScholarPubMed
14. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014; 511, 421427.CrossRefGoogle Scholar
15. Goldstein, JM, Cherkerzian, S, Seidman, LJ, et al. Sex-specific rates of transmission of psychosis in the New England high-risk family study. Schizophr Res. 2011; 128, 150155.CrossRefGoogle ScholarPubMed
16. Nomura, Y, Warner, V, Wickramaratne, P. Parents concordant for major depressive disorder and the effect of psychopathology in offspring. Psychol Med. 2001; 31, 12111222.CrossRefGoogle ScholarPubMed
17. van Os, J, van der, SY, Islam, MA, et al. Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience. Psychol Med. 2017; 47, 24212437.CrossRefGoogle ScholarPubMed
18. Klosterkotter, J, Hellmich, M, Steinmeyer, EM, Schultze-Lutter, F. Diagnosing schizophrenia in the initial prodromal phase. Arch Gen Psychiatry. 2001; 58, 158164.CrossRefGoogle ScholarPubMed
19. Uher, R, Cumby, J, MacKenzie, LE, et al. A familial risk enriched cohort as a platform for testing early interventions to prevent severe mental illness. BMC Psychiatry. 2014; 14, 344.CrossRefGoogle ScholarPubMed
20. First, MB, Spitzer, RL, Gibbon, M, Williams, JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition. (SCID-I/P). 2002.Google Scholar
21. Endicott, J, Spitzer, RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry. 1978; 35, 837844.CrossRefGoogle Scholar
22. NIMH. Family Interview for Genetic Studies (FIGS). https://www.nimhgenetics.org/interviews/figs/ 1992.Google Scholar
23. Kaufman, J, Birmaher, B, Axelson, D, et al. Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL 2013, DSM-5). Western Psychiatric Institute and Yale University 2013.Google Scholar
24. Arseneault, L, Cannon, M, Fisher, HL, et al. Childhood trauma and children’s emerging psychotic symptoms: a genetically sensitive longitudinal cohort study. Am J Psychiatry. 2011; 168, 6572.CrossRefGoogle ScholarPubMed
25. Miller, TJ, McGlashan, TH, Rosen, JL, et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull. 2003; 29, 703715.CrossRefGoogle ScholarPubMed
26. Fux, L, Walger, P, Schimmelmann, BG, Schultze-Lutter, F. The schizophrenia proneness instrument, child and youth version (SPI-CY): practicability and discriminative validity. Schizophr Res. 2013; 146, 6978.CrossRefGoogle ScholarPubMed
27. Schultze-Lutter, F, Ruhrmann, S, Fusar-Poli, P, et al. Basic symptoms and the prediction of first-episode psychosis. Curr Pharm Des. 2012; 18, 351357.CrossRefGoogle ScholarPubMed
28. Rabe-Hesketh, S, Skrondal, A, Pickles, A. Reliable estimation of generalized linear mixed models using adaptive quadrature. The Sata J. 2002; 2, 121.CrossRefGoogle Scholar
29. Goldstein, JM, Buka, SL, Seidman, LJ, Tsuang, MT. Specificity of familial transmission of schizophrenia psychosis spectrum and affective psychoses in the New England family study’s high-risk design. Arch Gen Psychiatry. 2010; 67, 458467.CrossRefGoogle ScholarPubMed
30. Turkheimer, FE, Bodini, B, Politis, M, et al. The X-linked hypothesis of brain disorders: can gender ratios tell us anything about cellular etiology of neurodegenerative and psychiatric diseases? Neuroscientist. 2015; 21, 589598.CrossRefGoogle ScholarPubMed
31. Lister, R, Mukamel, EA, Nery, JR, et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013; 341, 1237905.CrossRefGoogle ScholarPubMed
32. Xie, W, Barr, CL, Kim, A, et al. Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell. 2012; 148, 816831.CrossRefGoogle ScholarPubMed
33. Wray, NR, Ripke, S, Mattheisen, M, et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat Genet. 2018; 50, 668681.CrossRefGoogle ScholarPubMed
34. Bipolar Disorder Working Group of the Psychiatric Genomics Consortium. Genomewide association study identifies 30 loci associated with bipolar disorder. bioRxiv 2018; https://doi.org/10.1101/173062: 1-38.CrossRefGoogle Scholar
35. Wong, EH, So, HC, Li, M, et al. Common variants on Xq28 conferring risk of schizophrenia in Han Chinese. Schizophr Bull. 2014; 40, 777786.CrossRefGoogle ScholarPubMed
36. Homann, OR, Misura, K, Lamas, E, et al. Whole-genome sequencing in multiplex families with psychoses reveals mutations in the SHANK2 and SMARCA1 genes segregating with illness. Mol Psychiatry. 2016; 21, 16901695.CrossRefGoogle ScholarPubMed
37. Power, RA, Kyaga, S, Uher, R, et al. Fecundity of patients with schizophrenia, autism, bipolar disorder, depression, anorexia nervosa, or substance abuse vs their unaffected siblings. JAMA Psychiatry. 2013; 70, 2230.CrossRefGoogle ScholarPubMed
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