Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Butler, MI; Long-Smith, C; Moloney, GM; Morkl, S; O'Mahony, SM; Cryan, JF; Clarke, G; Dinan, TG.
The immune-kynurenine pathway in social anxiety disorder.
Brain Behav Immun. 2022; 99:317-326
Doi: 10.1016/j.bbi.2021.10.020
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Leal Garcia Sabrina
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: The tryptophan-kynurenine pathway is of major interest in psychiatry and is altered in patients with depression, schizophrenia and panic disorder. Stress and immune alterations can impact this system, through cortisol- and cytokine-induced activation. In addition, there is emerging evidence that the kynurenine pathway is associated with suicidality. There have been no studies to date exploring the immune-kynurenine system in social anxiety disorder (SAD), and indeed very limited human studies on the kynurenine pathway in any clinical anxiety disorder. METHODS: We investigated plasma levels of several kynurenine pathway markers, including kynurenine (KYN), tryptophan (TRYP) and kynurenic acid (KYNA), along with the KYN/TRYP and KYNA/KYN ratios, in a cohort of 32 patients with SAD and 36 healthy controls. We also investigated a broad array of both basal and lipopolysaccharide (LPS)-stimulated blood cytokine levels including IFN-γ, interleukin (IL)-10, IL-1β, IL-2, IL-4, IL-6, IL-8 and tumor necrosis factor (TNF)-α. RESULTS: SAD patients had elevated plasma KYNA levels and an increased KYNA/KYN ratio compared to healthy controls. No differences in KYN, TRYP or the KYN/TRYP ratio were seen between the two groups. SAD patients with a history of past suicide attempt showed elevated plasma KYN levels and a higher KYN/TRYP ratio compared to patients without a history of suicide attempt. No differences were seen in basal or LPS-stimulated pro-inflammatory cytokine levels between the patients and controls. However, unstimulated IL-10, an anti-inflammatory cytokine, was significantly lower in the SAD group. A significant sex influence was evident with SAD males having lower levels of IL-10 compared to healthy males but no difference seen between SAD females and healthy females. CONCLUSIONS: The peripheral kynurenine pathway is altered in SAD and preferentially directed towards KYNA synthesis. Additionally, kynurenine pathway activation, as evidenced by elevated KYN and KYN/TRYP ratio, is evident in SAD patients with a history of past suicide attempt. While no differences in pro-inflammatory cytokines is apparent in SAD patients, lower anti-inflammatory IL-10 levels are seen in SAD males. Further investigation of the role of the immune-kynurenine pathway in SAD and other clinical anxiety disorders is warranted.
- Find related publications in this database (Keywords)
- Tryptophan
- Kynurenine
- Kynurenic acid
- Social anxiety disorder
- Social phobia
- Anxiety
- Immunity
- Immune system
- Cytokines