Like Father Like Daughter: Sex-Specific Parent of Origin Effects in the Transmission of Liability for Psychotic Symptoms to Offspring

Alice Aylott, Alyson Zwicker, Lynn E. MacKenzie, Jill Cumby, Lukas Propper, Sabina Abidi, Alexa Bagnell, Helen Fisher, Barbara Pavlova, Martin Alda, Rudolf Uher

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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 examine 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 to 24 years (mean=13.1, SD=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. One-hundred-and-thirty (42%)
offspring had definite psychotic symptoms established in semi-structured interviews 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 (OR=2.65, 95%CI 1.43 to 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 to 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.
Original languageEnglish
JournalJournal of Developmental Origins of Health and Disease
Early online date29 Aug 2018
Publication statusE-pub ahead of print - 29 Aug 2018


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