OBJECTIVE: To study the association between parental depression and maternal 
antidepressant use during pregnancy with autism spectrum disorders in offspring.
DESIGN: Population based nested case-control study.
SETTING: Stockholm County, Sweden, 2001-07.
PARTICIPANTS: 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.
MAIN OUTCOME MEASURE: 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.
RESULTS: 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.
CONCLUSIONS: 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.