TY  - JOUR
PY  - 2022//
TI  - The immune-kynurenine pathway in social anxiety disorder
JO  - Brain, behavior, and immunity
A1  - Butler, Mary I.
A1  - Long-Smith, Caitriona
A1  - Moloney, Gerard M.
A1  - Morkl, Sabrina
A1  - O'Mahony, Siobhain M.
A1  - Cryan, John F.
A1  - Clarke, Gerard
A1  - Dinan, Timothy G.
SP  - 317
EP  - 326
VL  - 99
IS  - 
N2  - 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.<p /> <p>Language: en</p>
LA  - en
SN  - 0889-1591
UR  - http://dx.doi.org/10.1016/j.bbi.2021.10.020
ID  - ref1
ER  -