The immune-kynurenine pathway in social anxiety disorder.
Brain Behav Immun
; 99: 317-326, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34758380
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-1ß, 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Fobia Social
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article