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NEW RESEARCH LINKS SSRI TO AUTISM


Authors of a newly published study released on October 24, 2011, state that "Serotonin (5-HT) plays a key role in early brain development, and manipulation of 5-HT levels during this period can have lasting neurobiological and behavioral consequences." Researchers found that pregnant female rats exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants, specifically citalopram (Celexa), had pups that exhibited brain abnormalities and behaviors characteristic of those in autistic individuals.

Scientists found that rats given citalopram (Celexa), showed key signs of autism, including a disinterest in juvenile play, poor social behaviors as adults and abnormal responses to changes in their environment."[M]anipulation of 5-HT during early development in both in vitro and in vivo models disturbs characteristic chemoarchitectural and electrophysiological brain features, including changes is raphe and callosal connections, sensory processing, and myelin sheath formation. Also, drug-exposed rat pups exhibit neophobia and disrupted juvenile play behavior" according to the study. Ultimately, these findings conclude that "5-HT homeostasis is required for proper brain maturation . . ."

Researchers at the University of Mississippi Medical Center and the University of California, San Francisco administered citalopram to more than 200 rat pups at a time equivalent to the 3rd trimester and early infancy in humans and at dose levels comparable to drug concentrations administered in clinical practice. The findings suggest that fetal/infant exposure to SSRIs could be a factor in the rising diagnosis of autism spectrum disorders (ASD) in children.

"We saw behaviors in the treated rats and neurological problems that indicate their brains are not properly conducting and processing information," said researcher Dr. Rick C.S. Lin, professor of neurobiology and anatomical sciences at UMMC.

Scientists found that rats given citalopram (Celexa), showed key signs of autism, including a disinterest in juvenile play, poor social behaviors as adults and abnormal responses to changes in their environment. Treated rats also exhibited substantial developmental delays pertaining to the areas of the brain affecting sounds, listening and language. Autistic children often struggle with speech, language and reading, researchers noted. The study results "demonstrate that rat pups, when exposed perinatally to SSRIs, exhibit many behavioral traits often seen similarly in ASD."

Data also demonstrated that the brains of the treated rats had similar traits to the brains of autistic humans, including a thinner corpus callosum, which connects and serves as a communication bridge between the brain’s two halves. This fiber structure was disrupted in the treated rats’ brains in the same way seen in autistic individuals, researchers found. "The abnormalities in these rats would suggest the left and right sides of their brains are not communicating properly," said researcher Ian A. Paul. The study noted that this developmental defect is "reminiscent of MRI findings from ASD patients that show a reduction of human corpus callosum and the loss of long distance cortical connectivity."

Further, the autism-like effects of the SSRIs were seen more often and sometimes exclusively in treated male rats. This finding supports the idea that “male subjects may be more vulnerable to disruptions of the 5-HT (serotonin) system than their female counterparts are, just as [human] males are more likely to exhibit signs of ASD over [human] females.”

"These results demonstrate that rat pups, when exposed perinatally to SSRIs, exhibit behavioral traits often seen in ASD," said lead author Dr. Kimberly Simpson. Moreover, the study’s findings “are consistent with the possibility that dysregulation/dysfunction of the 5-HT system during early brain development may be the critical contributing factor in the etiology of ASD."

Researchers did say, however, that this study should be treated as a starting point for further research and that depressed pregnant women should confer with their doctors before stopping any antidepressant medication. "In this study we eliminated as many external factors as possible. But real-life situations are much more complex," researchers said.

The study, titled "Perinatal antidepressant exposure alters cortical network function in rodents," was published online on October 24, 2011 in the journal Proceedings of the National Academy of Sciences at www.pnas.org.


Summary Information

Title
Perinatal antidepressant exposure alters cortical network function in rodents

Authors
Kimberly L. Simpson 1,2 ; Kristin J. Weaver 1; Etienne de Villers-Sidani 5; Jordan Y.-F. Lu 1; Zhengwei Cai 4; Yi Pang 4; Federico Rodriguez-Porcel 2; Ian A. Paul 2,3; Michael Merzenich 5; Rick C. S. Lin 1,2

  1. Departments of Neurobiology and Anatomical Sciences, University of California, San Francisco
  2. Department of Psychiatry and Human Behavior, University of California, San Francisco
  3. Department of Pharmacology and Toxicology, University of California, San Francisco
  4. Division of Newborn Medicine, Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS
  5. W.M. Keck Center for Integrative Neuroscience, University of California, San Francisco

Journal
Proceedings of the National Academy of Sciences (Nov. 8, 2011), Vol. 108, No. 45: 18465-18470.  Published online before print, October 24, 2011

Funding
This research was supported by National Institutes of Health Grants RR017701 (to K.L.S. and I.A.P.), NS54278 and HD35496 (to Z.C.), and EUREKA MH084194 (to R.C.S.L.).



Additional Studies Linking Antidepressants to Autism

 


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