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Researchers at Johns Hopkins Review the Evidence for SSRI - Autism Link

While research into a possible link between maternal use of SSRI antidepressants and autism is still in its early stages, a recent review of the scientific evidence for such a link raises clear cause for concern. The review was conducted by researchers at the Johns Hopkins Bloomberg School of Public Health, the Johns Hopkins Medical Institutions, the Lurie Center for Autism at Massachusetts General Hospital for Children, and the University of California, Davis, M.I.N.D. Institute.

Three principle lines of evidence combine to suggest, as the authors do here, that there is "biologic plausibility that SSRIs could also directly harm the developing fetal brain and have physiological repercussions." First, it is well known that SSRI antidepressants like Celexa, Luvox, and many others have profound effects on serotonin, a chemical found in the brain and through the body that plays a central role in the transmission of nerve signals. It is also known that SSRIs cross the placenta, are found in the amniotic fluid, and "directly act on the fetus." High levels of serotonin could enter the developing brain of the fetus. Finally, it has been established that serotonin "plays an integral role in brain development and is recognized as being critical in very early developmental stages."

These three pieces of evidence, none of them contested, raise the possibility of serious consequences for a developing child. The authors suggest that SSRI antidepressants could create abnormal levels of serotonin in the mother, "thereby inducing deleterious effects on the fetus." By manipulating levels of serotonin while the prenatal brain is being wired, SSRIs could permanently affect how neurons in the child’s brain are formed and how they function, making the child "vulnerable for dysfunction later in life." The reviewers note that diverse studies have already provided "compelling evidence that there is serotonergic [involving serotonin, the brain chemical targeted by SSRIs] dysfunction in at least some individuals with autism." They also state that many of disorders that are often found in children with autism, such as epilepsy, sleep problems, self-injurious behaviors, and gastrointestinal symptoms, are disease processes that involve serotonin.

The authors note that "only one published study has focused on examining the association between prenatal SSRI exposure and a specific disorder – autism." In that study researchers used medical records from the Kaiser Permanente Medical Care Program in Northern California to identify children with autism spectrum disorders (ASD). They found that prenatal exposure to SSRIs the year before delivery doubled the odds of a child being diagnosed with ASD. The reviewers here suggest that this finding calls for "further exploration to confirm the association between the two." In view of the considerable evidence that suggests a concern about such an association is warranted, the paucity of research into the relationship between autism and maternal SSRI use reflects poorly, though not surprisingly, on the pharmaceutical industry and the makers of SSRI antidepressants. 

It should be noted that the prevalence of autism has increased dramatically in recent history. The authors of this review point out that the percentage of women using SSRIs during pregnancy increased from an estimated 1.2% in 1995 to 6.2% in 2005. According to one source, the prevalence of autism increased from 1 in 500 children to about 1 in 160 children during that same time period. Statistics from the Centers for Disease Control and Prevention place the 2005 prevalence rate even higher, at perhaps one in 120. In short, as SSRI use increased five-fold over a 10 year period, autism increased 3 to 4-fold. Today autism spectrum disorders are estimated to affect one in 88 children.

Summary Information

Title
Serotonin Hypothesis of Autism: Implications for Selective Serotonin Reuptake Inhibitor Use during Pregnancy

Authors
Rebecca A. Harrington¹; Li-Ching Lee¹; Rosa M. Crum²; Andrew W. Zimmerman³; Irva Hertz-Picciotto⁴

1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
2. Departments of Epidemiology, Psychiatry, and Mental Health, Johns Hopkins Medical Institutions, Baltimore, Maryland
3. Lurie Center for Autism, Massachusetts General Hospital for Children, Lexington, Massachusetts
4. Department of Public Health Sciences and the M.I.N.D. Institute, MSIC, University of California, Davis, Davis, California

Journal
Autism Research, 2013 June 1; 6(3):149-168. Published online March 14, 2013.

Funding
No information on funding was provided.

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