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Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study

BMJ 2013; 346 doi: (Published 19 April 2013) Cite this as: BMJ 2013;346:f2059

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Re: Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study

Dear Editor

Please find enclosed a letter of comments on the article: Rai D., Lee B. K., Dalman C., Golding J., Lewis G., Magnusson C. (2013) Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: Population based case-control study. B.M.J. 346: 1-15.

First, we wish to recognize the importance of retrospective population studies on the subject of factors that could be implicated in Autism Spectrum Disorder (ASD). As underscored in the study, retrospective population studies remain the main source of data because the absence of non-clinical markers of ASD renders prospective studies ethically unacceptable. However, the biases and confounders of such studies need to be properly assessed. This begs for some comments on the interpretation of the results provided in this study. The first two concern the absence of information regarding co-prescription medicines in addition to SSRIs.

(1). It is a known fact that over 30% of patients receiving an antidepressant are also prescribed and take a tranquilizer and/or hypnotic drug, essentially BZD [1]. The prescription of BZD has not been explored in connection with ASD. Nor for that matter has the joint effect of BZD with SSRIs. Furthermore, such a co-prescription, could be associated with certain forms of depression (with more or less irritability, or suicidal ideation) which, in and of themselves, may involve different transmission of neurodevelopmental impact on the developing fetus.

(2). Women with severe mental disorder were excluded from the study (cf. section Parental history of depression), but no information is provided on the existence or co-existence of obsessive compulsive disorder (OCD). OCD is associated with depression and its psychotropic treatment is often based on a specific SSRI medication. Therefore, IRSS prescription could actually be linked to both diagnoses individually and/or to co-morbid diagnosis. The subgroup of women with OCD ought not be overlooked as studies have shown that ASD and OCD may have common symptoms (mechanisms) [2].

One last separate comment concerns a surprising result bearing on the maternal population i.e. mothers of ASD cases are more often of local origin. This is surprising since migration is considered a globally stressful factor that increases risk of psychiatric disorder, specifically depression, both in adults and their offsprings. Conversely, mothers of ASD cases were older (this is common in all infants with pathological risk) but there is no information concerning assisted reproductive technique (ART): Older mothers have a higher risk of use of ART with or without gamete donation; this could also be a potential confounder in any interpretation of results.

We do agree with the main conclusion of the authors that it is necessary to enhance and implement more retrospective research on large population (perhaps with international pooling) on potential links between prescription of psychotropic medication, diagnosis of mental disorders during the peripartum and subsequent ASD symptomatology in offspring. However, up until now management of maternal affective health (mood disorder) during the peripartum still needs to be guided by current updated knowledge and case by case tailored management, navigating between Charybdis and Scylla [3].

[1] Ververs T, Kaasenbrood H, Visser G. et al. Prevalence and patterns of antidepressant drug use during pregnancy. Eur J Clin Pharmacol. 2006:62; 863-870.
[2] Russell AJ, Jassi A, Fullana MA, Mack H, Johnston K, Heyman I, Murphy DG, Mataix-Cols D. Cognitive behavior therapy for comorbid Obsessive-compulsive disorder in High-functioning autism spectrum disorders: A randomized controlled trial. Depression and Anxiety 2013 DOI 10.1002/da.22053.
[3] Rubinow D. (2006). Antidepressant treatment during pregnancy: between Scylla and Charybdis. Am J Psychiatry. 2006:163(6). 954-6.

Competing interests: No competing interests

17 May 2013
Gisèle Apter
Emmanuel Devouche, Jean-Louis Adrien (Paris Descartes University)
Erasme Hospital, Psychiatry and Psychopathology Research Institute
14 rue de l'abbaye, 92160 Antony, France