Regulation of emotional response in juvenile monkeys treated with fluoxetine: MAOA interactions

Abstract

Juvenile male rhesus macaques received therapeutic doses of fluoxetine daily from one to three years of age and were compared to vehicle-treated controls (N=16/group). Genotyping for monoamine oxidase A (MAOA) polymorphisms was used to form subgroups (N=8) with high and low expression of the gene. Behavioral responses were scored during 30-second exposures to pictures differing in affective content. As expected from its therapeutic effect, fluoxetine decreased the behavioral response to emotionally evocative pictures. A 44% reduction in number of expressive behaviors was seen, but only in subjects with low expression MAOA polymorphisms. In general, this effect occurred for pictures of varying affective content and was not due to altered occurrence of one specific behavior or type of behavior. The drug*genotype interaction was seen after one and two years of treatment and did not reverse one year after discontinuation of dosing. Two potential translational implications are suggested: (1) MAOA genetic polymorphisms may be the source of some of the variability in response to fluoxetine treatment in children; (2) extended fluoxetine treatment during juvenile brain development may result in persistent effects on emotional regulation.

Cognitive performance of juvenile monkeys after chronic fluoxetine treatment

“…We have previously reported that growth was not generally compromised by the treatment ( Golub et al, 2015a ). Fluoxetine effects on sleep ( Golub and Hogrefe, 2016 ), social interaction ( Golub et al, 2015b ), delay impulsivity ( He et al, 2014 ), and emotional response ( Golub et al, 2016 ), have also been reported from this study along with metabolomic biomarkers of fluoxetine action ( He et al, 2014 , Su et al, 2016 ).…”

“…All infants had been screened for temperament and response to stress with the BioBehavioral Assessment (BBA) ( Capitanio et al, 2006 ), a protocol applied colony-wide to assist in individual care and selection of subjects for research studies. BBA emotionality scores greater or less than 2 standard deviations from the colony mean were also used to eliminate potential subjects for this study ( Golub et al, 2016 ). Finally, the monkeys had been genotyped for the HTTLPR polymorphisms of the serotonin transporter (SERT) gene, as well as for monoamine oxidase A polymorphisms ( Karere et al, 2012 ).…”

Fluoxetine Administration in Juvenile Monkeys: Implications for Pharmacotherapy in Children

“…Monkeys were shown pictures with neutral, positive affective, and negative affective content. Vocalizations, facial expressions, and behaviors associated with emotional response were scored from videotape ( 6 ).…”

“…Emotional response was the major domain from our project that demonstrated a fluoxetine effects primarily associated with one MAOA genotype ( 6 ) (Figure 3 ; Table S2 in Supplementary Material). Low-MAOA subjects treated with fluoxetine were less emotionally reactive than their vehicle-treated counterparts.…”

“… Social interaction: fluoxetine effect on sum of all social interactions did not persist (unpublished data). Emotional response: emotional response was decreased in the low-MAOA genotype monkeys, as was the case during dosing, but the statistical test was not significant ( p = 0.18) ( 6 ). …”