The Antecedents of Schizophrenia: A Review of Birth Cohort Studies

Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, QLD 4076, Australia.
Schizophrenia Bulletin (Impact Factor: 8.45). 05/2009; 35(3):603-23. DOI: 10.1093/schbul/sbn084
Source: PubMed Central


Birth cohort (BC) studies demonstrate that individuals who develop schizophrenia differ from the general population on a range of developmental indices. The aims of this article were to summarize key findings from BC studies in order to identify areas of convergence and to outline areas requiring further research.
We define BC studies as studies based on general population BCs where data are collected prospectively from birth or childhood and which identify schizophrenia or related disorders as an outcome. To identify such studies, we searched various electronic databases using the search parameters (schizo* OR psych*) AND (birth cohort). We also checked the references of relevant articles and previous reviews.
We identified 11 BCs from 7 countries that have examined schizophrenia as an outcome in adulthood. There is relatively consistent evidence that, as a group, children who later develop schizophrenia have behavioral disturbances and psychopathology, intellectual and language deficits, and early motor delays. Evidence with respect to alterations in language, educational performance, and physical growth has also been identified in some studies. BC studies have also contributed evidence about a wide range of putative risk factors for schizophrenia.
BC studies have provided important, convergent insights into how the developmental trajectory of individuals who develop schizophrenia differs from their peers. The combination of new paradigms and larger cohorts, with the tools of modern epidemiology and biomedical science, is advancing our understanding of the developmental pathways to schizophrenia.

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Available from: Peter Jones, Sep 02, 2014
    • "risk factors (Murray et al., 1985). On the other hand, an intriguing finding in psychosis research is that, despite schizophrenia and other psychoses running in families, most affected individuals do not have family history of the illness (Welham et al., 2009). There is now increasing evidence suggesting that cognitive dysfunction is a reliable and stable feature of psychosis (Barch and Ceaser, 2012) and that it predicts psychosocial functioning and functional capacity better than clinical manifestations in schizophrenia patients (Bowie et al., 2008). "
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    ABSTRACT: Introduction: Phenotype definition of psychotic disorders has a strong impact on the degree of familial aggregation. Nevertheless, the extent to which distinct classification systems affect familial aggregation (ie, familiality) remains an open question. This study was aimed at examining the familiality associated with 4 nosologic systems of psychotic disorders (DSM-IV, ICD-10, Leonhard's classification and a data-driven approach) and their constituting diagnoses in a sample of multiplex families with psychotic disorders. Methods: Participants were probands with a psychotic disorder, their parents and at least one first-degree relative with a psychotic disorder. The sample was made of 441 families comprising 2703 individuals, of whom 1094 were affected and 1709 unaffected. Results: The Leonhard classification system had the highest familiality (h (2) = 0.64), followed by the empirical (h (2) = 0.55), DSM-IV (h (2) = 0.50), and ICD-10 (h (2) = 0.48). Familiality estimates for individual diagnoses varied considerably (h (2) = 0.25-0.79). Regarding schizophrenia diagnoses, Leonhard's systematic schizophrenia (h (2) = 0.78) had the highest familiality, followed by latent class core schizophrenia (h (2) = 0.74), DSM-IV schizophrenia (h (2) = 0.48), and ICD-10 schizophrenia (h (2) = 0.41). Psychotic mood disorders showed substantial familiality across nosologic systems (h (2) = 0.60-0.77). Domains of psychopathology other than reality-distortion symptoms showed moderate familiality irrespective of diagnosis (h (2) = 0.22-0.52) with the deficit syndrome of schizophrenia showing the highest familiality (h (2) = 0.66). Conclusions: While affective psychoses showed relatively high familiality estimates across classification schemes, those of nonaffective psychoses varied markedly as a function of the diagnostic scheme with a narrow schizophrenia phenotype maximizing its familial aggregation. Leonhard's classification of psychotic disorders may be better suited for molecular genetic studies than the official diagnostic systems.
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    • "However, the population studies mentioned above have been carried out with samples of non-clinical participants that have never been admitted. Moreover, both retrospective and prospective birth cohort studies have found that social isolation in childhood is associated with a later diagnosis of schizo Q4 phrenia (Jones et al., 1994; Cannon et al., 2008; Welham et al., 2009). In a cohort study of 50,054 Swedish conscripts, individuals who later developed psychotic experiences at a 15-year follow up were significantly more likely to have fewer than two friends and to prefer smaller groups (Malmberg et al., 1998) suggesting that social isolation may predate the onset of symptoms and the diagnosis. "
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    ABSTRACT: Recent work has focused on the role of the environment in psychosis with emerging evidence that specific psychotic experiences are associated with specific types of adversity. One risk factor that has been often associated with psychosis is social isolation, with studies identifying isolation as an important feature of prodromal psychosis and others reporting that social networks of psychotic patients are smaller and less dense than those of healthy individuals. In the present study, we tested a prediction that social isolation would be specifically associated with formal thought disorder. 80 patients diagnosed with psychosis-spectrum disorder and 30 healthy participants were assessed for formal thought disorder with speech samples acquired during an interview that promoted personal disclosure and an interview targeting everyday topics. Social isolation was significantly associated with formal thought disorder in the neutral interview and in the salient interview, even when controlling for comorbid hallucinations, delusions and suspiciousness. Hallucinations, delusions and suspiciousness were not associated with social isolation when formal thought disorder was controlled for. Formal thought disorder is robustly and specifically associated with social isolation. Social cognitive mechanisms and processes are discussed which may explain this relationship as well as implications for clinical practice and future research.
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    • "Birth cohort studies were originally designed to study early health outcomes, but as the earliest birth cohorts started in the 1940s to the 1960s have matured, adult outcomes have also been studied [1]. Welham and colleagues [1] reviewed birth cohort studies on antecedents of schizophrenia, finding 11 birth cohorts from seven countries. The authors concluded that birth cohort studies have provided important insights into how the premorbid developmental trajectory of individuals who develop schizophrenia differs from their peers. "
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    ABSTRACT: Birth cohort designs are useful in studying adult disease trajectories and outcomes, such as schizophrenia. We review the schizophrenia research performed in the Northern Finland Birth Cohort 1966 (NFBC 1966), which includes 10,934 individuals living in Finland at 16 years of age who have been monitored since each mother’s mid-pregnancy. By the age of 44, 150 (1.4%) had developed schizophrenia. There are 77 original papers on schizophrenia published from the NFBC 1966. The early studies have found various risk factors for schizophrenia, especially related to pregnancy and perinatal phase. Psychiatric and somatic outcomes were heterogeneous, but relatively poor. Mortality in schizophrenia is high, especially due to suicides. Several early predictors of outcomes have also been found. Individuals with schizophrenia have alterations in brain morphometry and neurocognition, and our latest studies have found that the use of high lifetime doses of antipsychotics associated with these changes. The schizophrenia research in the NFBC 1966 has been especially active for 20 years, the prospective study design and long follow-up enabling several clinically and epidemiologically important findings. When compared to other birth cohorts, the research in the NFBC 1966 has offered also unique findings on course and outcome of schizophrenia.
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