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Depression is very common in adolescence and is associated with a high risk of recurrence and suicide. Adolescents with depression experience the same symptoms as adults, such as sadness and fatigue, but some key differences exist. Depressed youth often feel irritable rather than or in addition to feeling low.

Despite being a common disorder, the pharmacological treatments available to treat depression in adolescence are scarce. Fluoxetine (or Prozac) is the only antidepressant licensed for use in the UK, still, very little is known about how this medication works in the brain of young people. This lack of knowledge constrains the development of new drugs.

A new study from the Psychopharmacology and Emotional Research Lab (PERL), A single dose of fluoxetine reduces neural limbic responses to anger in depressed adolescents, recently published in Translational Psychiatry, showed the effects of a single dose of fluoxetine on neural responses to emotional faces in depressed adolescents. Recent work from the PERL suggests that fluoxetine reduces the processing of anger, consistent with its effect for the treatment of irritability in young people (Capitão et al, 2015, Psychological Medicine). Hence, it could be predicted that fluoxetine would reduce the neural processing of angry faces.

Twenty-nine adolescents with Major Depressive Disorder (MDD), who had been recently prescribed fluoxetine by their psychiatrist, were randomised to receive their initial dose of 10mg fluoxetine vs. placebo. In line with predictions, after the single dose of fluoxetine, participants displayed reduced neural activity to angry facial expressions in a limbic region of the brain (a cluster that includes both the amygdala and the hippocampus), relative to placebo. Simultaneously, activity in the dorsal anterior cingulate cortex (dACC), known to be involved in self-regulation, was found to be increased. These results indicate that antidepressants may reduce the salience and/or increase the regulation of anger cues in young people with depression, right from the start of treatment.

The current study provides the first experimental evidence that, similarly to adults, antidepressants have immediate effects on emotional neural processing in young people within hours of administration and well before the therapeutic effects on mood emerge. The effect on anger is consistent with previous work and could therefore represent a key mechanism of action for subsequent improvement in symptoms of anger/irritability frequently seen in this population. Future studies should further explore the clinical implications of these effects, but it is hoped that these findings will assist the development of effective drug targets for adolescent depression, an area of research urgently needed.

Read the open-access paper in Translational Psychiatry.
www.nature.com/articles/s41398-018-0332-2

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