PET imaging of serotonin transporter in monkeys: Effects of maternal separation, and long-term fluoxetine treatment during adolescence

Background: Major depressive disorder (MDD) is a serious disorder that often begins following stress during adolescence. Selective serotonin reuptake inhibitors (SSRIs) are a common treatment for both adolescent and adult MDD. While MDD's early onset and available efficacy data support use of SSRIs in adolescents, concerns about safety have arisen, based on associations with suicidal behavior in adolescents, coupled with minimal data on long-term effects on the developing brain. This study used rhesus monkeys as a model to study the long term effects of both early life stress and chronic antidepressant treatment during adolescence (2-year of age) on the serotonin transporter. Methods: Thirty-two monkeys were randomly assigned to one of four groups (8 monkeys/group). They were peer-reared (PR) vs. mother-reared (MR), and with or without fluoxetine treatment. For PR, monkeys were separated from mothers at birth and nursery-reared until 6 months of age and thereafter housed with their peers. Chronic fluoxetine treatment began at 2-year of age for one year. One to two years post-washout, monkeys (average age of 5) were scanned with Positron Emission Tomography (PET) using [11C]DASB for serotonin transporter (SERT). Results: Our data from 32 monkeys (8 in each group) show 1. A significant global decrease in SERT binding in PR compared to MR monkeys, and 2. SERT binding is reversed in PR monkeys that received fluoxetine treatment. Conclusions: Our study demonstrates serotoninergic alterations in PR monkeys, and chronic fluoxetine treatment may reverse deficits in SERT density that is persistent more than one year after medication discontinuation.