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.
Homberg
Judith R
JR
Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands. j.homberg@cns.umcn.n
Schubert
Dirk
D
Gaspar
Patricia
P
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D015398:Signal Transduction / Q000187:drug effects
D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors