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

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.

A Canadian perspective on the developmental origins of health and disease: understanding the past as a way forward

“…Letourneau et al 19 tested the theory of intergenerational transmission of stress and found maternal adverse childhood experiences were predictive of mood and anxiety during pregnancy and postpartum, and externalising problems in the children, especially boys. Aylott et al 20 further confirmed this opposite-sex-specific parent-of-origin effect in the etiology of psychotic symptoms. Together these articles provide key insight into the gene-environment interactions that govern the intergenerational transmission of stress and the emergence of physical and mental illness and their transmission.…”

Prepregnancy obesity is associated with lower psychomotor development scores in boys at age 3 in a low-income, minority birth cohort

“…These characteristics may be linked to adverse outcomes and are important to consider in future work. Likewise, offspring body size may be on the causal pathway to adverse neurodevelopmental outcomes 93,94 and is strongly correlated with maternal BMI and GWG; 95 however, we were unable to examine the effects of child body size on associations at this age. There was potential for selection bias due to inclusion restrictions in our analyses; to examine for this potential bias, we conducted several sensitivity analyses, including IPW, and the results did not change meaningfully.…”

“…Although we were not able to account for paternal characteristics, evidence indicates that preconception paternal stressors, including nutrition status, metabolic dysregulation, psychosocial distress, and environmental contaminants, transform the preconception paternal epigenome and are reflected in the germline and offspring phenotype. [88][89][90][91][92] Intergenerational transmission of the preconception environment may play a fundamental role in neurodevelopment [92][93][94] and should be examined in future investigations. Additionally, breastfeeding data were limited, and breastfeeding continuation was not recorded after child age 1.…”

Intergenerational Transmission of Inequality in Psychological Health

“…It has been observed that psychotic symptoms were more common among the female children when their fathers also had psychotic features and conversely, symptoms in the male child were linked to maternal possession of psychotic symptoms. A genetic transmission linked to the X-chromosome was observed to be the etiological factor for the transmission across generations (51). Research evidences on transmission of Schizophrenia spectrum disorder also point towards a major role of environmental factors, in addition to the genetic susceptibility.…”