Abstract
Depression in adolescence is frequently characterised by symptoms of irritability. Fluoxetine is the antidepressant with the most favourable benefit:risk ratio profile to treat adolescent depression, but the neural mechanisms underlying antidepressant drugs in the young brain are still poorly understood. Previous studies have characterised the neural effects of long-term fluoxetine treatment in depressed adolescents, but these are limited by concurrent mood changes and a lack of placebo control. There is also recent evidence suggesting that fluoxetine reduces the processing of anger in young healthy volunteers, which is consistent with its effect for the treatment of irritability in this age group, but this remains to be investigated in depressed adolescents. Here we assessed the effects of a single, first dose of 10 mg fluoxetine vs. placebo on neural response to anger cues using fMRI in a sample of adolescents with Major Depressive Disorder (MDD) who had been recently prescribed fluoxetine. As predicted, adolescents receiving fluoxetine showed reduced activity in response to angry facial expressions in the amygdala-hippocampal region relative to placebo. Activity in the dorsal anterior cingulate cortex (dACC) was also increased. No changes in symptoms were observed. These results demonstrate, for the first time in depressed adolescents, that fluoxetine has immediate neural effects on core components of the cortico-limbic circuitry prior to clinical changes in mood. The effect on anger is consistent with our previous work and could represent a key mechanism through which fluoxetine may act to alleviate irritability symptoms in adolescent depression.
Highlights
Adolescence is a developmental period in which the risk of experiencing psychological disorders increases significantly
FMRI data acquisition and analysis Details of functional magnetic resonance imaging (fMRI) data acquisition pre-processing and first-level analysis are provided in the Supplementary Information (SI)
We have previously reported that acute fluoxetine reduces the accuracy to detect angry facial expression recognition in young healthy volunteers[21]
Summary
Adolescence is a developmental period in which the risk of experiencing psychological disorders increases significantly. Adolescents with depression display the same symptoms as seen in adulthood, but there are some key differences: depressed youth often exhibit irritability rather than (or in addition to) low mood. This is reflected in the high rates of irritability reported in community and clinical youth samples with depression, varying between 30 and 85%3–5. Despite being a common disorder, the pharmacological treatments available to treat adolescent depression are limited, with only fluoxetine and escitalopram approved for use in the US and only fluoxetine in the UK This problem is exacerbated by the fact that we still know very little about the neuropsychological mechanisms
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