In previous issues of Schizophrenia Bulletin
evidence has been presented suggesting that environmental risk factors (prenatal stress/malnutrition/infection/hypoxia, paternal age, developmental trauma, urbanicity, cannabis, ethnic minority group, social fragmentation) may be associated with an increased risk for schizophrenia and psychotic symptoms, resulting in widespread geographical variation in incidence and prevalence.10
These studies have several themes in common that are summarized in box 1
. It is clear that much remains to be clarified. For example, although the research on individual environmental risk factors is mostly consistent, effect sizes have been derived from bias and confounding-prone observational research. Also, none of the hypothesized factors are likely necessary or sufficient nor are they specific for psychosis outcomes. Finally, variables such as ethnic group, urbanicity, or prenatal maternal malnutrition merely represent proxies for one or more nongenetic factors that remain to be identified.
Box 1. Common Themes of Recent Reviews on the Link Between the Environment and Schizophrenia
- 1. Most findings are derived from observational studies that can never conclusively exclude bias and confounding.
- 2. It is not clear to what degree genetic liability for psychosis is the origin of the environmental influence (eg, psychosis liability contributing to later cannabis use or maternal psychosis liability giving rise to pregnancy complications).
- 3. For the majority of environmental risk factors, the increase in risk is associated with exposure before adulthood, suggesting an interaction with developmental processes. For example, the risk-increasing effects of urbanicity, trauma, and cannabis use are limited to exposure during childhood and adolescence, suggesting they may create enduring liabilities that, in interaction with other factors, bring about psychotic disorder in adulthood.
- 4. Relative risks associated with environmental exposures are modest and none are likely necessary or sufficient. Indeed, for most, interactions with genetic risk factors are hypothesized and some gene-environment interactions using direct or indirect measures of genes and environments have been reported.
- 5. Many, if not most, of the environmental candidate factors represent proxies for as yet unidentified nongenetic effects. For example, while ethnic group and urbanicity can be readily used as categorical variables in statistical analyses, it is not known what underlying true environmental effect they may represent.
- 6. The evidence for a link between the environment and psychosis is for many risk factors, at least where this has been studied, not limited to the narrow syndrome of schizophrenia, but extending to broader psychometric expressions of psychosis in the form of psychotic-like symptoms or schizotypy.
- 7. None of the reported risk factors can claim a specific link to psychosis-all have been associated with a range of other psychiatric and somatic disorders.
Given these uncertainties, relatively little attention has been paid to what arguably constitutes the most challenging issue: is there any evidence for a plausible mechanism linking exposure to the environment to psychosis outcomes? How does the environment induce change in human beings so that enduring risk states or psychopathological outcomes may result? Rutter11
has argued that there are a number of ways in which the environment can impact on the individual to increase the risk for psychopathology, including effects on gene expression, effects on developmental programming of the brain, effects on neuroendocrine and neurotransmitter functioning, effects on patterns of interpersonal interactions that may shape risk for later psychopathology, and effects on affective and cognitive processing. Therefore, one way to validate the hypothesis of a link between the environment and psychosis is to examine to what degree the two may be plausibly linked to any of the above-mentioned cognitive or biological mechanisms. Given the fact that (1) it is unlikely that the extreme diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms and (2) it has been suggested that environmental exposures in schizophrenia may induce psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission,12–15
this particular suggestion will be examined in more detail, subsumed under the broad header of “sensitization.”