Do natural experiments have an important future in the study of mental disorders?

• Published in: Psychological medicine 2019-05, Vol.49 (7), p.1079-1088
• Main Authors: Thapar, Anita, Rutter, Michael
• Format: Article
• Language: English
• Subjects: Adult; Attention deficit hyperactivity disorder; Bias; Bipolar disorder; Birth weight; Cardiovascular disease; Causality; Child; Cigarette smoking; Clinical trials; Conduct disorder; Convergence; Forecasting; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Hyperactivity; Invited Review; Mental disorders; Mental Disorders - diagnosis; Mental Disorders - epidemiology; Mental Disorders - genetics; Mental Disorders - psychology; Negative events; Negative life events; Parenting - psychology; Parents & parenting; Prenatal care; Prenatal experience; Prenatal exposure; Prevalence; Probability; Research Design - trends; Risk; Risk factors; Schizophrenia; Smoking; Uterus
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291718003896

There is an enormous interest in identifying the causes of psychiatric disorders but there are considerable challenges in identifying which risks are genuinely causal. Traditionally risk factors have been inferred from observational designs. However, association with psychiatric outcome does not equate to causation. There are a number of threats that clinicians and researchers face in making causal inferences from traditional observational designs because adversities or exposures are not randomly allocated to individuals. Natural experiments provide an alternative strategy to randomized controlled trials as they take advantage of situations whereby links between exposure and other variables are separated by naturally occurring events or situations. In this review, we describe a growing range of different types of natural experiment and highlight that there is a greater confidence about findings where there is a convergence of findings across different designs. For example, exposure to hostile parenting is consistently found to be associated with conduct problems using different natural experiment designs providing support for this being a causal risk factor. Different genetically informative designs have repeatedly found that exposure to negative life events and being bullied are linked to later depression. However, for exposure to prenatal cigarette smoking, while findings from natural experiment designs are consistent with a causal effect on offspring lower birth weight, they do not support the hypothesis that intra-uterine cigarette smoking has a causal effect on attention-deficit/hyperactivity disorder and conduct problems and emerging findings highlight caution about inferring causal effects on bipolar disorder and schizophrenia.