National Institute of Mental Health
Autism Study

Autism spectrum disorders (ASD) are known to affect social interaction, communication, and cause restricted interest or escape from stimulation. In addition, the neurotransmitter targeted by SSRI (selective serotonin reuptake inhibitor) antidepressants, serotonin, has been found to play an important role in central nervous system development. 

In a study published in the 2011 issue of  the Anatomical Record, researchers exposed rats to three different antidepressants – two of them SSRIs, Celexa (generic name citalopram) and Prozac (known generically as fluoxetine) – and observed how that exposure affected "behaviors that can be closely linked with ASD." Included in those behaviors were social recognition, juvenile play behavior, sexual behavior, and response to novel objects and auditory and visual stimuli. "We hypothesized that early exposure to SSRIs… alters the development of sensory processing regions which might translate in an abnormal response to novel stimulus" and also impact "complex social interactions," wrote researchers with University of Mississippi Medical Center’s Department of Psychiatry and Human Behavior.

The researchers observed several behavioral effects similar to the behaviors exhibited in autism. The antidepressant-exposed rats exhibited an exaggerated immobility or "freezing" response in reaction to a novel tone and a reduced investigation and increased avoidance of novel objects. Exposed rats showed less social behavior than controls and sexual behavior in exposed males was disrupted.

The study's results also paralleled another aspect of autism disorders – the higher prevalence of ASD among men. "Our study has demonstrated for the first time that the early exposure to a given dose of SSRIs affects male rates more severely than females," researchers said. "Males showed greater restriction in their behaviors and were less prone to interact with a novel object."

The authors observed that "almost all of the behaviors disrupted by early SSRI exposure in the present studies are heavily dependent on intact olfactory and auditory function. They suggested that one possible explanation for their findings is that neonatal exposure to antidepressants damages the normal development of these functions, producing a "lasting disruption of normal sensory processing."

Summary Information

Title
Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders

Authors
Federico Rodriguez-Porcel ¹; Donald Green ²; Nidhi Khatri ³; Sharonda Swilley Harris ³; Warren L. May ⁴;
Rick C.S. Lin^1,5; Ian A. Paul^1,2,3

1. Department of Psychiatry & Human Behavior, University of Mississippi Medical Center,
   Jackson, Mississippi
2. Program in Neuroscience, University of Mississippi Medical Center,Jackson, Mississippi;
3. Department of Medical Pharmacology, University of Mississippi Medical Center, Jackson, Mississippi
4. Center of Biostatistics/Bioinformatics, University of Mississippi Medical Center, Jackson, Mississippi
5. Department of Anatomy, University of Mississippi Medical Center, Jackson, Mississippi

Journal
Anatomical Record 294:1726–1735 (2011)

Funding
Grant sponsors: NIMH, NCRR; Grant numbers: MH084194, RR017701

Additional Studies Linking Antidepressants to Autism