Toxoplasma gondii Effects on the Relationship of Kynurenine Pathway Metabolites to Acoustic Startle Latency in Schizophrenia vs. Control Subjects

作者：Bradley D. Pearce, Nicholas Massa, David R. Goldsmith, Zeal H. Gandhi, Allison Hankus, Alaaeddin Alrohaibani, Neha Goel, Bruce N. Cuthbert, Molly Fargotstein, Dana Boyd Barr, Parinya Panuwet, Victoria M. Brown, Erica Duncan · 发表于：Frontiers in Psychiatry · 年份：2020 · DOI：10.3389/fpsyt.2020.552743 · 被引用次数：6 · 研究领域：Tryptophan and brain disorders、Neuroscience of respiration and sleep、Toxoplasma gondii Research Studies

Background: Chronic infection with Toxoplasma gondii (TOXO) results in microcysts in the brain that are controlled by inflammatory activation and subsequent changes in the kynurenine pathway. TOXO seropositivity is associated with a heightened risk of schizophrenia (SCZ) and with cognitive impairments. Latency of the acoustic startle response, a putative index of neural processing speed, is slower in SCZ. SCZ subjects who are TOXO seropositive have slower latency than SCZ subjects who are TOXO seronegative. We assessed the relationship between kynurenine pathway metabolites and startle latency as a potential route by which chronic TOXO infection can lead to cognitive slowing in SCZ. Methods: Fourty-seven SCZ subjects and 30 controls (CON) were tested on a standard acoustic startle paradigm. Kynurenine pathway metabolites were measured using liquid chromatography-tandem mass spectrometry were kynurenine (KYN), tryptophan (TRYP), 3-hydroxyanthranilic acid (3-OHAA), anthranilic acid (AA), and kynurenic acid (KYNA). TOXO status was determined by IgG ELISA. Results: In univariate ANCOVAs on onset and peak latency with age and log transformed startle magnitude as covariates, both onset latency [F (1,61) = 5.76; p = 0.019] and peak latency [F (1,61) = 4.34; p = 0.041] were slower in SCZ than CON subjects. In stepwise backward linear regressions after stratification by Diagnosis, slower onset latency in SCZ subjects was predicted by higher TRYP (B = 0.42; p = 0.008) and 3-OHAA:AA (B ...