Reconceptualizing major depressive disorder as an infectious disease | Biology of Mood & Anxiety Disorders | Full TextIn the first study of this kind, germ-free (GF), specific pathogen-free (SPF), and gnotobiotic mice were compared in their response to restraint stress . GF mice exhibited higher levels of plasma ACTH and corticosterone and had lower levels of brain-derived neurotrophic factor in the cortex and hippocampus, compared to SPF mice. The elevated stress response of GF mice was normalized with administration of the bacterium Bifidobacterium infantis. Another rodent study showed that administration of B. infantis in rats reduced the levels of IFN-γ, TNF-α, and IL-6 following mitogen stimulation and altered tryptophan, 5-HIAA, and DOPAC levels in the frontal cortex and amygdala . Administration of the Lactobacillus rhamnosus strain in mice was shown to alter GABAergic expression in the brain: elevating GABAB1b mRNA in the cingulate and prelimbic cortices, while reducing it in hippocampus and amygdala, among other regions .