Depressive symptoms and immune transcriptional profiles in late adolescents

Abstract

BACKGROUND\nRates of depression increase and peak during late adolescence and alterations in immune processes are thought to be both a risk factor and outcome of depression. However, few studies have examined depression-immune dynamics among adolescents. Using a functional genomics approach, the current study examined whether depressive symptoms were associated with activation of a gene expression profile, characterized by upregulated expression of pro-inflammatory-related genes and downregulated expression of antiviral-related genes in a sample of older adolescents (Mage\u202f=\u202f18.37, SD\u202f=\u202f0.51).\n\n\nMETHOD\nParticipants (n\u202f=\u202f87) reported on their depressive symptoms during the past week using the CES-D, and provided blood samples for genome-wide transcriptional profiling of mRNA.\n\n\nRESULTS\nAdolescents with clinically-significant levels of depressive symptoms (CES-D\u202f≥\u202f16) exhibited upregulated expression of inflammation-related genes and downregulated expression of antiviral-related genes compared to their peers with lower levels of depressive symptoms (CES-D\u202f<\u202f16). Bioinformatics analyses suggested that this pattern of differential gene expression was mediated by greater activity of the pro-inflammatory transcription factor, nuclear factor-kappa B (NF-κB), and reduced activity of glucocorticoid receptors (GRs) and interferon response factors (IRFs). Additional analyses implicated monocytes, B cells, and dendritic cells as primary cellular sources of the observed gene expression patterns associated with depressive symptoms.\n\n\nCONCLUSION\nResults are consistent with past work demonstrating links between depression and altered immunity. They provide a molecular basis for these associations and suggest that the underlying molecular signature may emerge as early as late adolescence when rates of depression tend to increase.