Gut microbiome in adolescent depression

Abstract

Objectives: To examine the association of major depressive disorder (MDD) and selective serotonin reuptake inhibitor (SSRI) use with gut microbiome in older adolescents and younger adults.

Methods: Fifteen to 20-year-old participants within a month of starting an SSRI and unmedicated controls were enrolled in a longitudinal study. They underwent a diagnostic evaluation comprising self-completed and rater-administered questionnaires and clinical interview. They also provided a stool sample, which was stored at -80°C until DNA extraction. Microbial DNA was extracted with the MoBio PowerSoil kit, and the V4 region of the 16S rRNA was amplified and sequenced. Raw sequence data was processed with the LotuS pipeline. Only samples with no antibiotic exposure in the last 6 months and with >1000 quality filtered reads were included in the analysis.

Results: 160 participants (57.5% female, mean age 20.0±1.9 years, 29% taking SSRIs) were enrolled, comprising 110 MDD patients (60% in acute episode), 27 healthy controls, and 23 psychiatric controls. No significant group differences were observed in bacterial richness or alpha and beta diversity. Differential abundance analysis of bacterial taxa found no significant group differences at the phylum and genus levels. Neither being in a major depressive episode vs. remission nor using SSRIs was associated with differential bacterial composition.

Conclusions: In this sizeable sample of older adolescents, neither MDD nor SSRI use was associated with differences in gut bacterial microbiome. In this age group, the bi-directional interaction between the gut bacteria and brain may be more nuanced than in adults, requiring further investigation.

Figure 1:

Alpha diversity of bacterial microbiome by group. Statistical analysis was performed using a global Kruskal-Wallis test between the three groups and a Wilcoxon rank sum test between the two groups. Healthy Controls (n=27); participants with major depressive disorder (MDD, n=110); and participants with psychiatric disorders other than MDD (Psych Control, n=23).

Figure 2:

Beta diversity of bacterial microbiome by group. Two-dimensional principal coordinate analysis (PCoA) plots of Bray-Curtis dissimilarity index, unweighted and weighted UniFrac distances in healthy controls (n=27) and participants with major depressive disorder (MDD, n=110) or with psychiatric disorders other than MDD (psych controls, n=23). Axes represent the first two principal coordinates of the PCoA, and each point on the plot represents the bacterial microbiome of an individual stool sample (blue = healthy controls, red = MDD, orange = psych controls).

Figure 3:

Comparison of bacterial relative abundance at the phylum and genus levels by participant groups. Healthy controls (n=27), major depressive disorder (MDD) (n=110) and psychiatric disorders other than MDD (PsychCon) (n=23). To optimize visualization, taxa with less than 1% abundance are grouped together as “<1% abundant phyla/taxa”.

Figure 4:

PCoA plot of Bray-Curtis distance metrics by sex distribution of all the participants.