The hypothesis for the present study was that fluoxetine cou

The hypothesis for the present study was that fluoxetine could influence cognitive processes that mature during juvenile reverse transcriptase development. Specifically, sustained attention, recognition memory, and cognitive flexibility, cognitive abilities with a clear developmental trajectory in primates, were evaluated with automated touch screen testing like that used in children (Green et al., 2009; Luciana and Nelson, 2002; Syvaoja et al., 2015). Sustained attention was also assessed during dosing because this cognitive domain has been shown to be impaired during fluoxetine dosing in adult humans (Ramaekers et al., 1995; Riedel et al., 2005, 1999; Schmitt et al., 2002; Wingen et al., 2008). This report is from a larger, broadly targeted nonhuman primate study meant to help fill gaps in our knowledge of the developmental effects of fluoxetine in children. Genetic and environmental variables were also considered in the study. A pharmacokinetic study with multiple doses identified a dose in juvenile monkeys in the therapeutic range for children based on serum concentrations (Golub and Hogrefe, 2014a). 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). After completion of post-dosing cognitive testing, measurement of spine synapse density was conducted in brains of a subset of the subjects. Synaptic pruning is an important brain maturation process active in prefrontal cortex during the pre-pubertal stage of development in primates (Anderson et al., 1995; Bianchi et al., 2013; Bourgeois et al., 1994; Petanjek et al., 2011; Rakic et al., 1986). Dendritic synaptic remodeling is one of the aspects of neuronal plasticity under investigation as a mechanism of fluoxetine therapeutic action (Ampuero et al., 2013; Chen et al., 2016; Guidi et al., 2013; Hajszan et al., 2005; Kobayashi et al., 2010; Stagni et al., 2013). Hippocampus and prefrontal cortex were selected for study because they show histomorphometric changes in depressed patients (Licznerski and Duman, 2013) and because hippocampal spine density responds to fluoxetine in rodents (Hajszan et al., 2005). Thus, the impact of fluoxetine on spine synapses was an additional important goal of the study.
Methods and materials
Results
Discussion
Financial interests and conflicts of interest
Acknowledgements
Introduction During development, children learn how to adapt, or inhibit, their behaviour in accordance with exposure to various types of emotions (Cole et al., 2004). Particularly in the context of peer interactions and social activities, children rapidly detect implicit socio-emotional cues (e.g., facial expressions) and use appropriate strategies to regulate their emotions accordingly (Gross, 2002; Cole et al., 2004). For instance, whereas smiling faces will encourage answers and approach, a negative countenance will trigger behavioural regulation (e.g., inhibition) to avoid a potentially disturbing situation. This suggests that the impact of emotion on cognition depends on the arousal and valence of the stimulus (Pessoa, 2009). Although the development of emotion regulation strategies has important affective, cognitive and social consequences in children, behavioural and neuroimaging studies investigating this process are few and their results are discrepant. For instance, at the behavioural level, whereas Cohen Kadosh et al. (2014) reported that children (11–12 years old) encounter more attentional control difficulties in the context of fearful compared to happy faces (Cohen Kadosh et al., 2014), others have shown that emotional context alters response inhibition ability in children; however, this inhibition is equal to both happy and sad faces (Urben et al., 2012).