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

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-sexoffspring (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 assessedpsychotic 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

Visual memory and psychotic symptoms in youth

Background: Psychotic symptoms are common during childhood and adolescence and may indicate transdiagnostic risk of future psychiatric disorders. Lower visual memory ability has been suggested as a potential indicator of future risk of mental illness. The relationship between visual memory and clinician-confirmed definite psychotic symptoms in youth has not yet been explored. Methods: We examined visual memory and psychotic symptoms among 205 participants aged 7–27 years in a cohort enriched for parental mood and psychotic disorders. We assessed visual memory using the Rey Complex Figure Test (RCFT) and psychotic symptoms using validated semi-structured interview measures. We tested the relationship between visual memory and psychotic symptoms using mixed-effects logistic regression. Results: After accounting for age, sex, and family clustering, we found that psychotic symptoms were significantly associated with lower visual memory (OR = 1.80, 95% CI 1.06–3.06, p = 0.030). This result was unchanged after accounting for general cognitive ability. Conclusion: Lower visual memory performance is associated with psychotic symptoms among youth, regardless of general cognitive ability. This finding may inform future targeted early interventions.</p

Polygenic scores and onset of major mood or psychotic disorders among offspring of affected parents

Objective: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. Methods: Eight cohorts were combined to create a sample of 1,884 participants ages 2–36 years, including 1,339 offspring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5.1 years. PGSs were constructed for depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder (ADHD), schizophrenia, neuroticism, subjective well-being, p factor, and height (as a negative control). Cox regression was used to test associations between PGSs, family history of major mental illness, and onsets of major mood and psychotic disorders. Results: There were 435 onsets of major mood and psychotic disorders across follow-up. PGSs for neuroticism (hazard ratio=1.23, 95% CI=1.12–1.36), schizophrenia (hazard ratio=1.15, 95% CI=1.04–1.26), depression (hazard ratio=1.11, 95% CI=1.01–1.22), ADHD (hazard ratio=1.10, 95% CI=1.00–1.21), subjective well-being (hazard ratio=0.90, 95% CI=0.82–0.99), and p factor (hazard ratio=1.14, 95% CI=1.04–1.26) were associated with onsets. After controlling for family history, neuroticism PGS remained significantly positively associated (hazard ratio=1.19, 95% CI=1.08–1.31) and subjective well-being PGS remained significantly negatively associated (hazard ratio=0.89, 95% CI=0.81–0.98) with onsets. Conclusions: Neuroticism and subjective well-being PGSs capture risk of major mood and psychotic disorders that is independent of family history, whereas PGSs for psychiatric illness provide limited predictive power when family history is known. Neuroticism and subjective well-being PGSs may complement family history in the early identification of persons at elevated risk