Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 346: f2059

Centre for Mental Health, Addiction and Suicide Research, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.
BMJ (online) (Impact Factor: 17.45). 04/2013; 346(apr19 1):f2059. DOI: 10.1136/bmj.f2059
Source: PubMed


To study the association between parental depression and maternal antidepressant use during pregnancy with autism spectrum disorders in offspring.
Population based nested case-control study.
Stockholm County, Sweden, 2001-07.
4429 cases of autism spectrum disorder (1828 with and 2601 without intellectual disability) and 43 277 age and sex matched controls in the full sample (1679 cases of autism spectrum disorder and 16 845 controls with data on maternal antidepressant use nested within a cohort (n=589 114) of young people aged 0-17 years.
A diagnosis of autism spectrum disorder, with or without intellectual disability. EXPOSURES: Parental depression and other characteristics prospectively recorded in administrative registers before the birth of the child. Maternal antidepressant use, recorded at the first antenatal interview, was available for children born from 1995 onwards.
A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported. All associations were higher in cases of autism without intellectual disability, there being no evidence of an increased risk of autism with intellectual disability. Assuming an unconfounded, causal association, antidepressant use during pregnancy explained 0.6% of the cases of autism spectrum disorder.
In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability. Whether this association is causal or reflects the risk of autism with severe depression during pregnancy requires further research. However, assuming causality, antidepressant use during pregnancy is unlikely to have contributed significantly towards the dramatic increase in observed prevalence of autism spectrum disorders as it explained less than 1% of cases.

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    • "Hence, in many cases, autism is considered to be multifactorial, and other factors besides the mere genetic variation must play a role. Factors currently being studied include epigenetic modifications, perinatal problems (Kolevzon et al., 2007), intra-uterine testosterone levels (Auyeung et al., 2009; Baron-Cohen et al., 2015), immune dysfunction (Goines and Van de Water, 2010), pesticides (Roberts et al., 2007), in utero exposure to medication (Bromley et al., 2013; Rai et al., 2013), alterations to the gut microbiome (Mayer et al., 2014), and many others as reviewed by Herbert (Herbert, 2010). "
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    • "First, epidemiological evidence alone is typically insufficient to test the causal nature of hypothesized risk factors, and the causal role of many early risk factors remains uncertain (Thapar & Rutter, 2009). Second, as noted byRaj et al. (2013)even if one assumes causality, changes in relatively rare risk factors such as antidepressant use in pregnancy are unlikely to have any major effect on the overall population prevalence of common mental health problems. Third, there have also been notable improvements in early life conditions; for example, decreased exposure to maternal smoking in pregnancy (Ekblad, Gissler, Korkeila, & Lehtonen, 2014). "
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