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Research Roundup —The Tapestry of Environmental Influences in Psychosis

30 Oct 2010

31 October 2010. Epidemiological studies have been weaving a tapestry of environmental contributions to psychosis, even as studies about the latest “it” gene command more attention. From a recent survey to gauge the commonness of psychotic symptoms in nations around the world to studies that seek to clarify key threads of environmental data, these studies offer leads to factors that might explain why the identical twin of someone with schizophrenia has a good chance of avoiding the disease. They recognize that psychosis arises within a place, whether that place consists of a city or nation, a rung on the socioeconomic ladder, or the more intimate landscape of a brain affected by drugs. We now take the opportunity to survey some notable recent additions to the schizophrenia epidemiology literature.

Psychotic symptoms around the world

As if in defiance of DSM and ICD treatment of schizophrenia as a categorical disorder, psychotic symptoms appear in the absence of diagnosable disorders. However, limited research suggests that nations differ in the percentage of people who experience psychotic symptoms. In a new study, Somnath Chatterji of the World Health Organization (WHO), Geneva, Switzerland, and colleagues took a particularly thorough look at their prevalence in different nations. They examined nationally representative samples of 52 countries around the world and published their findings online in Schizophrenia Bulletin on September 13.

The researchers, including first author Roberto Nuevo of the Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain, analyzed data on 256,445 subjects from the WHO’s World Health Survey. They found that the percentage of subjects who reported experiencing psychotic symptoms over the past 12 months differed greatly from one country to the next. For example, less than 1 percent of those in Vietnam, versus 45.8 percent of those in Nepal, reported at least one symptom. Worldwide, 7.1 percent of subjects reported delusional mood, 8.4 percent delusions of reference and persecution, and 5.8 percent hallucinations, but only 1.0 percent had ever been diagnosed with schizophrenia. The percentage of subjects with a putative schizophrenia diagnosis also varied among nations, but to a lesser extent than individual symptoms.

Despite the prevalence differences, the health burden associated with psychotic symptoms remained constant across countries. In controlled analyses, even one symptom was enough to predict poorer health; additional symptoms came with increasingly worse outcomes in each of eight domains, including vision, mobility, self-care, cognition, interpersonal activities, pain and discomfort, sleep and energy, and affect. These findings led Nuevo and colleagues to call even mild psychotic symptoms without frank disorder “a problem of potential public health concern” that may warrant increased screening efforts, but not without awareness of the perils of stigmatization and treatment side effects.

A capsule of sunlight

One reason that some nations carry a heavy psychosis load may be their lack of sunshine. Clues that this may affect schizophrenia risk come from a body of work showing that subjects born in winter or early spring are more likely to develop the illness than those born in summer or fall, at least in the Northern Hemisphere (for a review and meta-analysis, see Davies et al., 2003). Vitamin D, which the body makes when sunlight hits the skin, may be involved.

In a high-latitude country like Denmark, summer sunlight lasts well into the evening hours, and winter daylight fades too soon. Little vitamin D can be made during the short winter days. These seasonal differences make the nation a good epidemiological laboratory for testing the relationship between vitamin D levels at birth and the risk of developing schizophrenia. Preben Mortensen, University of Aarhus, Denmark, and colleagues concluded that optimizing vitamin D levels could prevent a whopping 44 percent of schizophrenia cases there. They presented their findings in the September Archives of General Psychiatry.

The researchers, including first author John McGrath, Queensland Centre for Mental Health Research, Wacol, Australia, linked records from national registries to dried blood spots routinely collected from newborns. They compared 424 cohort members who had been diagnosed with schizophrenia to an equal number of matched control subjects. This revealed a reversed U-shaped relationship between vitamin D levels in the blood and schizophrenia risk. Subjects whose vitamin D levels fell into the lowest three quintiles had double the risk, although those in the highest quintile also had a slightly increased risk. McGrath and colleagues raise the “tantalizing prospect” that low-cost supplements might avert many cases of schizophrenia, but note that the nonlinear relationship, if confirmed, might make this tricky.

The ties that sensitize

Another environmental exposure linked to schizophrenia, cannabis use, often triggers fleeting psychotic symptoms in healthy people; it also predicts the emergence of outright psychosis (see SRF related news story and SRF news story). In the October 4 online edition of the Archives of General Psychiatry, a team led by Jim van Os of Maastricht University Medical Centre in the Netherlands, explored whether genetic risk for psychotic disorder goes hand-in-hand with sensitivity to the psychotomimetic effect of cannabis. The Genetic Risk and Outcome in Psychosis Group has recruited subjects from the Netherlands and Belgium, including 1,120 patients with nonaffective psychosis, their 1,057 siblings, and 590 control subjects whose first-degree relatives had never had psychosis.

The researchers compared subclinical psychotic experiences in patients versus their siblings to evaluate sensitivity to cannabis in those with increased genetic risk who shared other familial exposures. To examine sensitivity as a function of liability to psychotic illness, they examined schizotypal symptoms and behaviors in patients versus control subjects. The results showed that healthy siblings were much likelier than control subjects to show positive and negative schizotypy as a function of cannabis use. Furthermore, the severity of positive psychotic symptoms correlated more highly between siblings if the unaffected sibling used cannabis. Van Os and colleagues concluded that the association between genetic susceptibility and sensitivity to cannabis resulted from familial risk increasing sensitivity to cannabis rather than fostering cannabis use. In other words, people who are most genetically prone to schizophrenia are the ones most likely to experience psychotic symptoms if they partake of cannabis.

Psychosis and the city

Other well-known risk factors for schizophrenia include growing up in an urban rather than a rural setting, living in unfavorable neighborhoods, and migrating to another country (see SRF related news story; SRF news story; also see SRF Live Discussion on the social environment). Even so, doubt remains about whether they confer risk in themselves or piggyback on some other exposure. Three recent studies shed a neon light on their ties to psychosis.

A group led by Stanley Zammit, Cardiff University, Wales, U.K., performed a longitudinal study of 203,829 people, nearly everyone born in Sweden during a five-year period. In the September Archives of General Psychiatry, they describe how they used new multilevel statistical methods to probe the extent to which aspects of the person, school, municipality, and county explain the high risk of psychosis in urban areas. As it turned out, the risk of nonaffective psychosis related mainly to person-level factors, but the excess risk in urban areas mostly reflected social fragmentation in the schools. This measure indexes the fraction of students who migrated from another country, moved to or from another town, or grew up in single-parent homes.

Interactions between individual- and higher-level factors suggested that standing out in certain ways from most others in their school raised the risk of developing any psychosis. Specifically, subjects whose social fragmentation scores differed from most of their schoolmates and foreign-born students in schools full of natives showed extra risk. This brings to mind earlier reports of an ethnic density effect, whereby the risk of psychosis in ethnic minority subjects declines as the representation of their ethnic group in the region rises.

A paper released online by Psychological Medicine in September lends further support to this idea. Peter Schofield, Kings College London, and colleagues noted that ethnic density studies in the United Kingdom have yielded mixed results, perhaps because they assessed density within too broad an area. Instead, Schofield and colleagues focused on neighborhoods in South East London that housed one-fourth as many people as the larger wards usually studied. The results backed their suspicions: ethnic density at the neighborhood, but not the ward, level correlated with the incidence of psychosis in blacks during a 10-year period.

Although ethnic density made no difference for psychosis risk in whites, for blacks, living in a neighborhood in which 25 percent or fewer of the residents were also black tripled the risk of developing psychosis (odds ratio = 2.88, 95 percent confidence interval 1.89-4.39) relative to whites. In contrast, blacks whose neighborhoods were home to a higher-than-average percentage of blacks showed no increased risk. “We postulate that this protective effect is likely to be dependent on the social milieu within just a handful of streets, and that a sense of shared ethnicity is therefore felt more in social interactions with, for example, immediate neighbors and whom one meets on the way to the corner shop rather than with the broad ethnic composition of larger urban areas,” Schofield and colleagues write.

Another schizophrenia risk factor entangled with minority group status is socioeconomic hardship, the focus of a study in the October American Journal of Psychiatry. Susanne Wicks, Karolinska Institute, Stockholm, Sweden, and colleagues identified 13,116 adopted children using Swedish national registries. Adoptees whose biological parents had no history of psychosis were more likely to develop nonaffective psychosis if raised in families that experienced parental unemployment (hazard ratio = 2.0). Genetic risk seemed to aggravate the effects of this hardship on adopted children (hazard ratio = 15.0).

A little problem

The disadvantages faced by at least some ethnic minority groups who live in disadvantaged neighborhoods may include starting life too small (Janevic et al., 2010). To clarify the relationship between low birth weight and schizophrenia risk, Kathryn Abel, University of Manchester, U.K., and colleagues published a study in the September Archives of General Psychiatry. They linked national registries that covered 1.49 million births in Sweden and Denmark to records on 57,455 cases of adult psychiatric disorder, including 5,445 with schizophrenia.

Babies in the lowest birth-weight groups were most likely to develop schizophrenia later on, but the relationship between birth weight and risk extended into the normal range of birth weights and to other psychiatric diseases as well. According to Abel and colleagues, these findings suggest looking beyond the abnormal events, such as hypoxia and brain bleeding, that occur more often in the smallest babies (Cannon et al., 2002). They write, “This suggests that it might be appropriate to place equal emphasis on a broader understanding of the connections between fetal growth, its control, and brain development.” At the same time, they warn that low birth weight might be standing in for other risk factors. As in all of these studies, unsnarling the strands of correlated exposures and understanding how they might interact presents challenges.—Victoria L. Wilcox.


Nuevo R, Chatterji S, Verdes E, Naidoo N, Arango C, Ayuso-Mateos JL. The Continuum of Psychotic Symptoms in the General Population: A Cross-national Study. Schizophr Bull. 2010 Sep 13. Abstract

McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, Burne TH, Norgaard-Pedersen B, Hougaard DM, Mortensen PB. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry. 2010 Sep;67(9):889-94. Abstract

Genetic Risk and Outcome in Psychosis (GROUP) Investigators. Evidence That Familial Liability for Psychosis Is Expressed as Differential Sensitivity to Cannabis: An Analysis of Patient-Sibling and Sibling-Control Pairs. Arch Gen Psychiatry. 2010 Oct 4.

Wicks S, Hjern A, Dalman C. Social risk or genetic liability for psychosis? A study of children born in Sweden and reared by adoptive parents. Am J Psychiatry. 2010 Oct;167(10):1240-6. Epub 2010 Aug 4. Abstract

Schofield P, Ashworth M, Jones R. Ethnic isolation and psychosis: re-examining the ethnic density effect. Psychol Med. 2010 Sep 22:1-7. Abstract

Abel KM, Wicks S, Susser ES, Dalman C, Pedersen MG, Mortensen PB, Webb RT. Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies? Arch Gen Psychiatry. 2010 Sep;67(9):923-30. Abstract

Zammit S, Lewis G, Rasbash J, Dalman C, Gustafsson J-E, Allebeck P. Individuals, schools, and neighborhood: a multilevel longitudinal study of variation in incidence of psychotic disorders. Arch Gen Psychiatry. 2010 Sep;67(9):914-22. Abstract