The goal of this observational study is to learn about the role of the human gut microbiome in antidepressant treatment response in adolescents with Major Depressive Disorder (MDD). Specifically, the study aims to collect microbiota samples of adolescents treated with fluoxetine, over the span of 8-weeks, to:

• determine the influence of the microbiome on the efficacy of fluoxetine to treat adolescent depression.
• test whether the gut microbiome from different timepoints can predict ultimate success of fluoxetine
• investigate the interaction of gut microbiome composition and pharmacogenetic metabolizer status on steady-state plasma concentrations of fluoxetine.

Depression symptom severity will be evaluated upon enrollment and 6-weeks into antidepressant treatment.

For this project the investigators are interested in changes in the gut microbiome associated with adolescent depression and the influence of the microbiome on the efficacy of fluoxetine to treat adolescent depression. It is hypothesized that the composition of the human gut microbiome alters the response to fluoxetine of adolescents with depression. This study aims to collect gut microbiota of adolescents being treated with antidepressants at several timepoints to (1) determine the efficacy of fluoxetine to treat depression, (2) test whether the gut microbiome from different timepoints can predict ultimate success of fluoxetine, and (3) investigate the interaction of gut microbiome composition and pharmacogenetic metabolizer status on steady-state plasma concentrations of fluoxetine. Adolescent patients with clinically significant depressive symptoms who are prescribed fluoxetine, from Rady Children's Hospital San Diego (RCHSD) Inpatient Child and Adolescent Psychiatry Services (CAPS), will be recruited for this study. Up to twelve stool samples are planned to be collected, including prior to start of antidepressant treatment for a baseline measure of gut microbiome composition, daily samples over during the first week of fluoxetine treatment, and then biweekly collections until the end of the 8-week study duration.

Inclusion Criteria:

• Subjects from all ethnic backgrounds will be eligible to participate.
• Having clinically significant depressive symptoms based on a score >40 on the Children's Depression Rating Scale-Revised
• Prescribed more than 5mg of Fluoxetine (Prozac)
• Has an identifiable legal guardian.

Exclusion Criteria:

• Has been taking a standing psychotropic medication in the past 6 months
• Has been taking antibiotics or metformin during the past 6 months (known strong effects on gut microbiome)
• Admitted to RCHSD CAPS post-overdose (potential strong effects on gut microbiome)
• Currently using nicotine-containing substances (known strong effects on gut microbiome)

Adolescents ages 13-17 with depression diagnosis