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ICOSR 2015—A Closer Look at Early Risk Factors for Psychosis

18 May 2015

As part of our ongoing coverage of the 2015 International Congress on Schizophrenia Research (ICOSR), held March 29 through April 1 in Colorado Springs, we bring you session summaries from some of the participants in the Young Investigator program. We are, as always, grateful for the gracious assistance of conference directors Carol Tamminga and Chuck Schulz, as well as meeting staff Cristan Tamminga and Dorothy Denton. For this report, we thank Simona A. Stilo of the Institute of Psychiatry at King's College London.

May 19, 2015. On Tuesday morning, March 31, at the International Congress on Schizophrenia Research, researchers gathered for a symposium titled, "At risk from conception: epidemiological evidence for early risk factors for psychosis." Numerous studies have now shown that patients with schizophrenia more frequently have a history of obstetric complications (OCs) than normal subjects (Murray and Lewis, 1987; Cannon et al., 2002; Geddes et al., 1999). Environmental hazards in pregnancy linked to the disorder include marked prenatal nutritional deprivation (Susser and Lin, 1992), hypovitaminosis D (McGrath et al., 2004), and elevated third-trimester homocysteine levels (Brown et al., 2007). In addition, prenatal infections such as influenza (Brown et al., 2004), rubella (Brown et al., 2000), and Toxoplasma gondii (Mortensen et al., 2007) may play a role, as may advanced paternal age (Malaspina et al., 2001). Social factors such as urban birth, urban upbringing, and urban residence have been associated with an increased risk of psychosis (Lewis et al., 1992; Kelly et al., 2010). Other identified risk factors are being a member of a minority group (Boydell et al., 2001; Fearon et al., 2006) and traumatic experiences in childhood (Bebbington, 2009; Morgan and Fisher, 2007; Bendall et al., 2008; Stilo et al., 2013; Shah et al., 2014). Thus, a body of evidence suggests that early environmental factors may increase risk of psychosis, particularly in the presence of other known risk factors (e.g., genetic risk).

The speakers in this symposium examined several epidemiological risk factors for psychosis as well as protective factors. Environmental risk factors are good targets for prevention, as they may be modifiable and provide promising opportunities to unravel psychosis etiology.

James Scott of the University of Queensland in Brisbane, Australia, set the scene by presenting data on pre-pregnancy obesity and risk of psychosis in offspring. Evidence shows that obesity is increasing globally (Kim et al., 2007; Heslehurst et al., 2011). However, only four studies in the literature have specifically looked at maternal obesity and risk of schizophrenia (Jones et al., 1998; Schaefer et al., 2000; Kawai et al., 2004; Wahlbeck et al., 2001), and they were limited by the inability to adjust for plausible confounding factors. Using data from a 21-year longitudinal study conducted in Australia, Scott and colleagues replicated previous studies showing that pre-pregnancy BMI was significantly higher in the mothers of offspring who experienced any hallucinations or delusions at 21 years and extended previous results by adjusting for low SES and birth complications as plausible confounders. Scott suggested mechanisms that might explain this association, including a direct effect of obesity through inflammation or dysregulation of maternal hormonal systems, and an indirect effect through birth complications or nutrient changes.

The second presenter, Jaana Suvisaari of the National Institute for Health and Welfare in Helsinki, Finland, presented her research on risk of schizophrenia spectrum disorders (SSDs) and minority status, focusing on protective factors. The author compared risk of SSDs in the Swedish-speaking minority who have higher socioeconomic positions and longer life expectancy, with risk of SSDs in the Finnish-speaking majority, in a representative sample of 47,445 Finns (Suvisaari et al., 2014). After adjusting for sex, parental ages at birth, paternal employment around conception, parental psychosis, and place and residence in the capital, belonging to the Swedish-speaking minority was associated with lower risk of SSDs, supporting the role of social factors as protective factors. The author explained the result as the effect of fewer negative childhood exposures; lower divorce rates; higher wealth, wages, education and employment rates; higher social and community participation; and larger social networks. The effect was larger for males than females, and larger for those born in the capital area than those born elsewhere in Finland.

In the attempt to identify modifiable risk factors that affect brain development, Alan Brown of Columbia University in New York City hypothesized that low maternal free thyroxine (T4) is related to an increased risk of schizophrenia in offspring in a cohort of 1,010 case-control pairs. After taking into account several confounders, maternal low free T4 was associated with offspring schizophrenia, suggesting the utility of assessing the effect of screening and treating early gestational hypothyroxinemia to prevent offspring neurodevelopmental problems including schizophrenia.

The session concluded with a presentation by Vera Morgan of the University of Western Australia in Perth, who examined whether exposure to social stressors in childhood, including timing of exposure, is a risk factor for psychotic illness. The author compared social stressors in a large cohort of 15,486 offspring born to mothers with a lifetime history of psychotic illness with a cohort of 452,459 offspring born in the same period to mothers with no known psychiatric history. Odds of psychotic illness increased significantly following exposure to childhood abuse and discontinuity in parenting, including death and hospitalization. Length and age of exposure impacted on risk. However, children at increased familial risk for psychosis were also at increased risk of experiencing the social stressors, indicating the need to disentangle the impact of social stressors from familial liability.

The discussant, John McGrath of the University of Queensland in Brisbane, Australia, rounded out the symposium by reflecting on the need to identify modifiable risk factors that affect brain development and the need to disentangle the impact of social stressors from other competing risks for psychosis illness, including familial liability. To this end, he said, "Nations represent the laboratory for epidemiologists." McGrath also noted the increasing importance of identifying mechanisms explaining association between early environmental risk factors and psychosis, the need to consider mediating factors, and a broad range of confounding factors, and to further explore protective factors. Indeed, there is much in this field that needs further investigation: Vera Morgan suggested that some risk factors may lead to other risk factors, and Robin Murray of the Institute of Psychiatry at King's College London noted that genetic factors may influence the occurrence of so-called environmental risk factors.—Simona Stilo.