New perspectives on the neurodevelopmental effects of SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for the treatment of depression and anxiety-related disorders. These drugs target the serotonin transporter (5-HTT) and increase serotonin signalling. Although chronic SSRI administration has few reported side effects, recent observations suggest that it could have long-term effects on neurodevelopment. First, 5-HTT is transiently expressed in many brain areas during development. Second, 5-HTT blockade during development causes wiring defects in these areas. These effects are seen most clearly in the sensory systems. Third, the behavioural effects of 5-HTT blockade during development are sometimes dramatically different from the effects of 5-HTT blockade during adulthood. Most of this evidence was collected from studies with 5-HTT knockout mice and rats. However, the phenotypes associated with low or high functioning 5-HTT alleles in humans can result from similar developmental alterations in 5-HT levels. Here, we review the existing evidence on the long-term effects of developmental SSRI exposure.