Background. Despite extensive research the etiology of schizophrenia remains unclear. Whilst a substantial body of research points to a developmental component where early risk factors and maturational processes interact to culminate in psychosis during adulthood, key components and processes are yet to be confirmed. Prospective birth cohort studies, with their longitudinal data drawn from the general population, are vital to better understanding these pathways. To date, birth cohort (BC) studies have found that compared to healthy individuals, those who develop schizophrenia are more likely to display subtle deviations in certain developmental domains during infancy, childhood or adolescence. Yet there had been no recent review of these findings to identify areas of agreement, disagreement or where information was lacking. Aims. The overall aim of this dissertation is two-fold: firstly to identify and consolidate the current literature related to the antecedents of schizophrenia based on birth cohort studies; and secondly to undertake empirical studies based on an Australian birth cohort to address specific issues raised in the preceding review. Methods. The following three papers present empirical studies which use common methods based on an Australian birth cohort. Each study was based on a birth cohort of 3801 young adults born between 1981 and 1984, as part of the Mater University Study of Pregnancy and its outcomes. An extensive range of behavioural, cognitive, physical and social measures had been taken at various stages during their development namely, antenatally, at birth and six months, and at 5, 14 and 21 year follow-ups. Psychiatric diagnoses were obtained at age 21 follow-up from the Composite International Diagnostic Interview (CIDI), or, if this was not available, on a self-report health outcomes checklist; this produced the outcome variable ‘screen-positive non-affective psychosis’ (SP-NAP). The association between antecedents and later SP-NAP were examined using logistic regression adjusted for potentially confounding variables (such as actual age at assessment, cannabis use in adolescence, and gender). Each study also (a) examined differences in case vs. noncase maturation over time; and (b) conducted planned sensitivity and post hoc analyses, such as for source of diagnoses and predictive validity. Analyses were performed using SAS 9.2 (SAS). Results. The main findings of the review were that BC studies of schizophrenia provide important insights into both the maturational antecedents of schizophrenia and putative risk modifying factors. Yet while some antecedents, such as neurocognitive dysfunction, have been well documented, others are less certain (such as postnatal physical growth). There are no studies based on pre-morbid attentional measures. In addition, there were no studies of developmental pathways where continuity of maturation was based on within-individual scores rather than group means. These findings led to three empirical studies based on an Australian birth cohort previously untapped in psychosis research. The first study found that higher levels childhood and adolescent general psychopathology increased the risk of SP-NAP. This effect was less clear for females and when adolescent psychopathology had been rated by mothers at the 14-year follow-up. In contrast, self-reported hallucinations at the 14 year follow-up increased the risk of SP-NAP in both sexes. Males with high psychopathology scores in both childhood and adolescence were at greatest risk, followed by males and females whose ‘social, attention and thought’ scores were either consistently dysfunctional or worsened from childhood to adolescence (3- to 13-fold risk). The second study found that altered physical growth in infancy and adulthood (increased head circumference and height) raised the risk of SP-NAP for females but not males. For cases, there was no evidence of ‘catch-up growth’, i.e., growth retardation at birth being followed by a period of rapid growth. There was also no group difference in pubertal maturation for males or females. The final study found that dysfunction in childhood and adolescent intelligence, attention and speech increased the risk of SP-NAP for males but not females. Males with persistently high scores or who worsened on measures related to childhood and adolescent attentional problems were at greatest risk of SP-NAP. Discussion. While there are some caveats, disturbed developmental antecedents – particularly psychopathology and impaired cognition in males – were more frequently identified in cohort members who developed non-affective psychosis than their peers. More specifically, this disturbed development appeared be in domains which reflect those of the adult disorder and include the possible endophenotypes of psychosis-like experiences, inattention and visuospatial dysfunction. Of interest, self-rated items during adolescence were associated with increased risk of later psychosis. Finally, developmental pathways associated with non-affective psychosis were not uniform in timing but varied depending on such factors as domain and gender. These findings stress that understanding the heterogeneity in developmental pathways is crucial to understanding the heterogeneous nature of the subsequent disorder.
| Identifer | oai:union.ndltd.org:ADTP/279415 |
| Creators | Joyce Welham |
| Source Sets | Australiasian Digital Theses Program |
| Detected Language | English |
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