Abstract and Introduction
Abstract
Background and Hypothesis: Psychotic disorders are associated with a growing number of recognized environmental exposures. Cumulative exposure to multiple environmental risk factors in childhood may contribute to the development of different patterns of schizotypy evident in early life. Hypotheses were that distinct profiles of schizotypy would have differential associations with a cumulative score of environmental risk factors.
Study Design: We prospectively examined the relationship between 19 environmental exposures (which had demonstrated replicated associations with psychosis) measured from the prenatal period through to age 11 years, and 3 profiles of schizotypy in children (mean age = 11.9 years, n = 20 599) that have been established in population data from the New South Wales-Child Development Study. Multinomial logistic regression was used to examine associations between membership in each of 3 schizotypy profiles (true schizotypy, introverted schizotypy, and affective schizotypy) and exposure to a range of 19 environmental risk factors for psychosis (both individually and summed as a cumulative environmental risk score [ERS]), relative to children showing no risk.
Results: Almost all environmental factors were associated with at least 1 schizotypy profile. The cumulative ERS was most strongly associated with the true schizotypy profile (OR = 1.61, 95% CI = 1.52–1.70), followed by the affective (OR = 1.33, 95% CI = 1.28–1.38), and introverted (OR = 1.32, 95% CI = 1.28–1.37) schizotypy profiles.
Conclusions: Consistent with the cumulative risk hypothesis, results indicate that an increased number of risk exposures is associated with an increased likelihood of membership in the 3 schizotypy profiles identified in middle childhood, relative to children with no schizotypy profile.
Introduction
Schizotypy refers to a collection of traits that reflect latent liability for schizophrenia,[1–3] and provides a conceptual framework for a developmentally informed understanding of schizophrenia-spectrum disorders.[4,5] Schizotypy encompasses mild reality distortion (ie, psychotic-like experiences [PLEs]), alongside aberrations in cognitive, interpersonal, and affective functioning and can be thought of as an intermediate phenotype on the developmental pathway to schizophrenia-spectrum disorders.[4] Consistent with contemporary models of schizophrenia,[6–8] schizotypy is thought to result from the interaction of environmental exposures with a genetic diathesis in a series of transactional processes across development, which may progress to clinical disorder.[2,3] Currently, the majority of developmental research on psychosis has focused on high-risk states close to the onset of the disorder,[5] and there is a lack of evidence regarding what types of environmental factors are associated with schizotypy in childhood.
Previous research has mostly focused on singular environmental risk factors for schizotypy (eg, childhood trauma,[9] pregnancy and obstetric complications,[10] and cannabis use).[11] However, no environmental factor in isolation is sufficient to cause mental illness.[12] The cumulative risk hypothesis proposes that an accumulation of risk factors impacts the development of cognitive, social, and emotional brain networks on the pathway to clinical disorder.[13] There are different methods used to operationalize cumulative environmental risk, with the most common being a sum score of binary indicators of environmental risk factors, known as an environmental risk score (ERS).[14] More recently, researchers have derived weighted environmental sum scores that account for variations in effect sizes of the associations between each environmental exposure and the outcome of interest.[15] Using summed or weighted ERSs to understand environmental factors is advantageous because children are likely to contend with constellations of risk factors during development rather than isolated single risk factors.[16] Furthermore, understanding the interaction between proximal (individual) and distal (structural) risk factors is important because these commonly co-occur, possibly reflecting causal links or shared background factors,[17] and they may be mediated through the same or similar biological pathways (eg, hypothalamic-pituitary-adrenal (HPA) axis dysregulation).[18]
Recent evidence has shown that ERSs are associated with the diagnosis of psychotic disorders, including schizophrenia,[7,15,19–26] and that systematic exposure-wide approaches to measuring cumulative environmental risk predict psychopathology more generally.[27,28] Importantly, environmental risk appears to be associated not just with psychotic disorder, but with subclinical expressions of the psychosis spectrum, including PLEs (representing the "reality distortion" or "positive" features of schizotypy) and schizotypy more broadly.[29] One study found evidence for an association between an ERS and PLEs in late adolescence/adulthood, that was independent of genetic influence,[30] and another found that an ERS and PLEs interacted additively with other dimensions of psychopathology that constitute other features of schizotypy (eg, negative symptoms) to predict psychosis-spectrum disorders.[31] Furthermore, a study in a general population adult sample found that an ERS that was associated with the diagnosis of schizophrenia in a previous study was likewise associated with schizotypal features in adult healthy controls and unaffected relatives.[32] To the best of our knowledge, no study has examined the relationship of an ERS with PLEs or schizotypy in middle childhood specifically, but there is evidence of association between a range of environmental factors and PLEs during middle childhood.[33]
Evidence is mixed as to whether environmental risk factors that have evidence of associations with schizophrenia are differentially associated with distinct facets of schizotypy. For example, only cognitive-perceptual (but not interpersonal or cognitive disorganization) features of schizotypy have been found to be associated with urbanicity[34] and cannabis use.[35] In contrast, family history of schizophrenia has been associated with interpersonal and disorganized (but not cognitive-perceptual features) of schizotypy,[36] and likewise, polygenic risk[37] has been associated with interpersonal and affective features (eg, anergia and asociality) but not cognitive-perceptual features. These inconsistent findings could reflect that the pattern or co-occurrence of traits within an individual (rather than dimensional measures of single traits) may differentially relate to certain risk factors.[3,38,39] That is, it may be that there are different paths to the development of schizophrenia—operating via different patterns of schizotypy evident in the general population—that each may reflect more or less biological and/or environmental influence.[40]
In the current study, we extend previous studies of environmental risk and schizotypy from a developmental perspective, with a view that different patterns of schizotypy evident in childhood may be differentially impacted by an accumulation of environmental risk factors in early life. We used data from a cohort of 20 599 Australian children with linked administrative records (drawn from the New South Wales-Child Developmental Study [NSW-CDS] population cohort)[41,42] to examine the relationship between 3 previously established person-centered childhood profiles of schizotypy[39] and a range of environmental risk factors occurring from the prenatal period up until age 11 years, that each had replicated associations with psychotic disorders. Our aim was to determine whether distinct profiles of schizotypy showed differential association with individual environmental risk factors or, via calculation of both a summed and weighted ERS, the combined effects of a broad range of environmental risk factors.
Schizophr Bull. 2023;49(2):244-254. © 2023 Oxford University Press
