Main findings

In a rural-provincial, general population cohort, parental psychotic experiences were associated with an approximately 2-fold risk of psychotic experiences in offspring, showing similar effects of paternal and maternal psychotic experiences. The findings were robust in multivariate models, also when including general mental health problems of the youths. While maternal, but not paternal, depression, anxiety, and poor mental well-being were associated with psychotic experiences in offspring, parental psychotic experiences remained the only factor significantly associated with offspring psychotic experiences in the multivariate models, suggesting some specificity of subclinical psychosis expression. Finally, there was evidence of dose-response, as having two parents (rather than just one) with psychotic experiences was more strongly associated with a 3-4-fold risk of psychotic experiences in offspring.

Methodological considerations

The current study benefited from a large sample size of parents and their offspring that were assessed independently yet using the same measure for psychotic experiences. The findings were consistent and robust across numerous statistical models, increasing the confidence in the findings. However, some limitations should be considered. First, regarding measurement of psychotic experiences, self-report measures of psychotic experiences might be considered overinclusive, yet the overlap between self-reported and clinically assessed psychotic experiences is reasonable (Gundersen et al., Reference Gundersen, Goodman, Clemmensen, Rimvall, Munkholm, Rask and Jeppesen2019; Kelleher, Harley, Murtagh, & Cannon, Reference Kelleher, Harley, Murtagh and Cannon2011), and even psychotic experiences that are not verified clinically seem to have clinical importance in both adults and youths (Monshouwer et al., Reference Monshouwer, ten Have, Tuithof, van Dorsselaer, Bak, Gunter and de Graaf2023; Rimvall et al., Reference Rimvall, Gundersen, Clemmensen, Munkholm, Larsen, Skovgaard and Jeppesen2019). However, clinically important information about the degree of distress due to psychotic experiences (Karcher et al., Reference Karcher, Barch, Avenevoli, Svaill, Huber, Simon and Loewy2018), was not thoroughly assessed in the current study using a shortened version of the PLIKSq. Further, although the questions for the PLIKS-interview were based on questions from Diagnostic Interview Schedule for Children–IV (DISC–and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), the PLIKSq lacks formal validation. Second, the recurrence of psychotic experiences (as opposed to remitting psychotic experiences) is an important marker of clinical severity (Staines et al., Reference Staines, Healy, Cotter, Kelleher, Murphy and Cannon2023), which could not be considered in parents nor youths, given the cross-sectional nature of the current study. Third, information on diagnosed/diagnosable psychotic disorders was not available for neither parents nor youths or other relatives, and we cannot rule out, that the findings in part might reflect associations between parental and offspring psychotic symptomatology higher on the continuum than the level of subclinical psychotic experiences. Further, we could not assess to which degree the findings that psychotic experiences clustered in families were due to genetic effects or environmental effects within the families or more broadly. Also, potential (sub)culturally accepted expression of psychotic experiences, e.g. specific religious or paranormal beliefs, which might cluster in families, was not assessed. Fourth, due to non-participation, there is a risk of selection bias. Prior attrition analyses based on half of all participants in the LOFUS cohort (Jepsen et al., Reference Jepsen, Wingstrand, Abild, Ellervik, Simonsen, Rasmussen and Andersen2020b), showed that participants were more often female and had fewer socioeconomic adversities compared to non-participants, likely resulting in less variation and somewhat biasing the reported associations towards the null. Because register data for the entire cohort is not yet available, we could not conduct specific attrition analyses for the current sample, yet we can fairly assume that our sample was similarly subject to differential attrition and positively selected. Additionally, further selection bias could have been introduced as fathers were particularly underrepresented in the current sample compared to mothers, likely largely attributable to the fact that more than 80% of children of divorced parents in Denmark have their household address with their mothers (Ottosen, Stage, & SFI - Det Nationale Forskningscenter for Velfærd, Reference Ottosen and Stage2012). Lastly, although reliable administrative data was utilized to link family members (Pedersen, Reference Pedersen2011), a genetic link between the youth and both parents is not ensured (nor tested) in all cases, but this would be the case in the vast majority of participants.

Finally, the rural context of the current cohort could be considered, as evidence suggests that psychotic disorders are less prevalent in rural areas (Vassos, Pedersen, Murray, Collier, & Lewis, Reference Vassos, Pedersen, Murray, Collier and Lewis2012). However, the evidence for an association between urbanicity and psychotic experiences is not as strong (DeVylder et al., Reference DeVylder, Kelleher, Lalane, Oh, Link and Koyanagi2018), and the prevalence of definite psychotic experiences according to PLIKSq among 11-17-year-olds in LOFUS (17.2%) was almost identical with a report from the Danish Copenhagen Child Cohort 20000 (16.7%) from a mainly suburban population (Rimvall et al., Reference Rimvall, van Os, Verhulst, Wolf, Larsen, Clemmensen and Jeppesen2020b).

Interpretation

While prior findings from general population- and high risk cohorts are not entirely consistent in showing an association between parental psychotic disorders and offspring psychotic experiences, our findings corroborate the majority of studies indicating a transgenerational transmission of psychotic symptoms/experiences (Gregersen et al., Reference Gregersen, Møllegaard Jepsen, Rohd, Søndergaard, Brandt, Ellersgaard and Elgaard Thorup2022; Jeppesen et al., Reference Jeppesen, Larsen, Clemmensen, Munkholm, Rimvall, Rask and Skovgaard2015b; Karcher et al., Reference Karcher, Barch, Avenevoli, Svaill, Huber, Simon and Loewy2018; MacKenzie et al., Reference MacKenzie, Abidi, Fisher, Propper, Bagnell, Morash-Conway and Uher2016; Polanczyk et al., Reference Polanczyk, Moffitt, Arseneault, Cannon, Ambler, Keefe and Caspi2010). Additionally, in keeping with our findings, a prior study has shown clustering of positive psychosis symptomatology across the psychosis continuum within families in a smaller study of adults (Hanssen et al., Reference Hanssen, Krabbendam, Vollema, Delespaul and Van Os2006). A key argument behind the idea that psychosis can advantageously be viewed on a continuum in the population, is the presence of shared environmental and genetic risk factors between psychotic experiences and psychotic disorders (van Os, Kenis, & Rutten, Reference van Os, Kenis and Rutten2010). The current findings, that psychotic experiences in parents were robustly associated with psychotic experiences in offspring, lend support to the idea that the familial effects of positive psychotic phenomena should be considered on a continuum.

Evidence clearly indicates that psychotic experiences by no means solely reflect (risk of) psychotic disorders in youths and adults alike (Healy et al., Reference Healy, Brannigan, Dooley, Coughlan, Clarke, Kelleher and Cannon2019; Kaymaz et al., Reference Kaymaz, Drukker, Lieb, Wittchen, Werbeloff, Lataster and van Os2012), and subclinical psychotic symptomatology is likely more advantageously viewed as a transdiagnostic phenotype (van Os & Reininghaus, Reference van Os and Reininghaus2016). However, several studies do indeed indicate some specificity of psychotic experiences across generations (Gregersen et al., Reference Gregersen, Møllegaard Jepsen, Rohd, Søndergaard, Brandt, Ellersgaard and Elgaard Thorup2022; Jeppesen et al., Reference Jeppesen, Larsen, Clemmensen, Munkholm, Rimvall, Rask and Skovgaard2015b), as well as larger effects of psychotic experiences in youths on psychotic v. non-psychotic disorders later in life according metanalytic evidence (Healy et al., Reference Healy, Brannigan, Dooley, Coughlan, Clarke, Kelleher and Cannon2019). Regarding genome-wide informed studies, meta-analytic evidence suggests shared genetic vulnerability between schizophrenia and psychotic experiences (Ronald & Pain, Reference Ronald and Pain2018). Subsequently, evidence from more than 100 000 individuals using data from the UK biobank showed that polygenic risk score for schizophrenia were indeed associated with psychotic experiences (Legge et al., Reference Legge, Jones, Kendall, Pardiñas, Menzies, Bracher-smith and Walters2019). However, there was strong evidence of non-specificity, given that polygenic risk scores for depression, bipolar-, and neurodevelopmental disorders were all associated with psychotic experiences (Legge et al., Reference Legge, Jones, Kendall, Pardiñas, Menzies, Bracher-smith and Walters2019). The evidence of non-specificity of the polygenic risk scores strengthens the notion of psychotic experiences as also environmentally dependent (on factors such as substance misuse, socioeconomic adversities in the family, and trauma) markers of transdiagnostic risk of mentally ill health (van Os & Reininghaus, Reference van Os and Reininghaus2016). Such environmental factors likely explain an important part of the variance in the findings in the current study.

Strikingly, in this general population sample we showed that psychotic experiences were indeed strongly and robustly associated across generations, whereas the role of parental depression, anxiety, and mental well-being were not independently associated with psychotic experiences in offspring in the mutually adjusted statistical models. Also, after further adjustment for general mental health problems of the child, the association between parental and youth psychotic experiences remained. Hence, the current study adds to the notion of specificity of subclinical psychotic expression by presenting novel evidence of familial clustering of psychosis at the lower end of the psychosis continuum. The findings in the current study might both reflect primary genetic effects of psychotic psychopathology as well as psychosocial distress and other detrimental social and environmental factors that might cluster in families (Bolhuis et al., Reference Bolhuis, Steenkamp, Tiemeier, Blanken, Pingault, Cecil and El Marroun2022; Newbury et al., Reference Newbury, Arseneault, Caspi, Moffitt, Odgers, Belsky and Fisher2022; Taylor, Freeman, Lundström, Larsson, & Ronald, Reference Taylor, Freeman, Lundström, Larsson and Ronald2022), and are likely to interact (Taylor et al., Reference Taylor, Freeman, Lundström, Larsson and Ronald2022). The dose-response finding in the current study (increased risk of psychotic experiences in youths when both parents reported psychotic experiences) might also reflect both shared genetic and environmental vulnerabilities. While it is well appreciated that prediction of clinical psychosis syndromes through clinical high-risk paradigms for psychosis is a very challenging task, especially in youths (Catalan et al., Reference Catalan, Salazar de Pablo, Vaquerizo Serrano, Mosillo, Baldwin, Fernández-Rivas and Fusar-Poli2021; Lång et al., Reference Lång, Yates, Leacy, Clarke, McNicholas, Cannon and Kelleher2022), the assessment of subclinical psychosis expression could improve the early identification of vulnerable youths, and wide-spread assessment of psychotic experiences has been suggested to inform identification of younger individuals at increased risk of developing severe psychopathology broadly (Cotter, Healy, Staines, Mongan, & Cannon, Reference Cotter, Healy, Staines, Mongan and Cannon2022).

The current study further calls for systematic consideration of the family systems that the youths are part of in clinical practice, as well as a family history of mental health problems beyond merely considering clinical diagnoses in relatives. Although we have presented evidence of specificity of psychosis vulnerability, based on the larger body of literature, we warn against assuming diagnostic specificity of psychotic experiences in families, but rather as vulnerability markers that should be considered within the broader context of the familial and social risks. Future studies may benefit from describing longitudinal patterns of psychotic experiences within family systems to further advise us on whether assessment of psychotic experiences in youths can contribute to targeting more in-depth assessments and possible service provision, particularly in families with clustering of psychotic experiences.