Zoloft May Cause Cognitive Improvements in Children with Fragile X Syndrome


Children with fragile X showed some gains in development, cognition, and social skills after treatment with Zoloft.

Young children with fragile X syndrome given sertraline (Zoloft) saw small, but crucial improvements in cognition and social participation during a recent study.

Fragile X syndrome, also known as Martin-Bell syndrome, is a genetic condition that causes a range of developmental issues, which includes cognitive impairment and learning disabilities, according to Genetics Home Reference. Approximately 60% of children with this disease are also diagnosed with autism.

A study published in the Journal of Developmental & Behavioral Pediatrics was the first controlled clinical trial of low-dose Zoloft, a selective serotonin reuptake inhibitor (SSRI), in young children with fragile x-syndrome. Between February 2012 and August 2015, researchers enrolled children between the ages of 2- and 6-years-old with fragile X syndrome.

Since it’s more common for males to be more severely affected by the disorder than females, a majority of children in the study were male and Caucasian. There were 52 children who completed the 6-month clinical trial, with about half of the children given low-dose Zoloft titrated to their age and size, and the other half given placebo.

Researchers assessed the children’s cognitive and social functioning at regular intervals, using measurements that included tests to assess cognition, visual reception, fine motor skills, expressive and receptive language, sensory processing, and social participation.

“Sertraline not only demonstrated an effect on certain aspects of development and cognition, but also showed evidence of social improvements,” said senior study author Randi Hagerman. “Further, we found significant improvement in early expressive language development among children with autism and fragile X syndrome who received the drug rather than placebo.”

During early development when synapse formation is most rapid, serotonin levels are low. This suggests that an SSRI could be beneficial during that developmental window in the first 5 years of life.

Furthermore, mouse models show that SSRIs stimulate brain-derived neurotrophic factor when given during early development.

“Given the lack of maturation of synapses in fragile X syndrome, along with BDNF’s role in synaptic maturation, plasticity, and neurogenesis, SSRIs are of particular interest for the treatment of fragile X syndrome,” Hagerman said.

The study authors concluded that the developmental window of rapid synapse formation and network connectivity in the first few years of life may be the best time to deliver a beneficial treatment.

“This study suggests that further trials to replicate these preliminary results and studies, coupled with enhanced language/educational interventions, are warranted in fragile X syndrome and in autism spectrum disorder,” Hagerman said.

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