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

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 = 3.68; p = 0.007), and lower KYN:TRYP (B = −185.42; p = 0.034). In regressions with peak latency as the dependent variable, slower peak latency was predicted by higher TRYP (B = 0.47; p = 0.013) and 3-OHAA:AA ratio (B = 4.35; p = 0.010), and by lower KYNA (B = −6.67; p = 0.036). In CON subjects neither onset nor peak latency was predicted by any KYN metabolites. In regressions stratified by TOXO status, in TOXO positive subjects, slower peak latency was predicted by lower concentrations of KYN (B = −8.08; p = 0.008), KYNA (B = −10.64; p = 0.003), and lower KYN:TRYP ratios (B = −347.01; p = 0.03). In TOXO negative subjects neither onset nor peak latency was predicted by any KYN metabolites.Conclusions: KYN pathway markers predict slowing of startle latency in SCZ subjects and in those with chronic TOXO infection, but this is not seen in CON subjects nor TOXO seronegative subjects. These findings coupled with prior work indicating a relationship of slower latency with SCZ and TOXO infection suggest that alterations in KYN pathway markers may be a mechanism by which neural processing speed, as indexed by startle latency, is affected in these subjects.

Rapid recovery following short-term acoustic disturbance in two fish species

Noise from human activities is known to impact organisms in a variety of taxa, but most experimental studies on the behavioural effects of noise have focused on examining responses associated with the period of actual exposure. Unlike most pollutants, acoustic noise is generally short-lived, usually dissipating quickly after the source is turned off or leaves the area. In a series of experiments, we use established experimental paradigms to examine how fish behaviour and physiology are affected, both during short-term (2 min) exposure to playback of recordings of anthropogenic noise sources and in the immediate aftermath of noise exposure. We considered the anti-predator response and ventilation rate of juvenile European eels ( Anguilla anguilla ) and ventilation rate of juvenile European seabass ( Dicentrarchus labrax ). As previously found, additional-noise exposure decreased eel anti-predator responses, increased startle latency and increased ventilation rate relative to ambient-noise-exposed controls. Our results show for the first time that those effects quickly dissipated; eels showed rapid recovery of startle responses and startle latency, and rapid albeit incomplete recovery of ventilation rate in the 2 min after noise cessation. Seabass in both laboratory and open-water conditions showed an increased ventilation rate during playback of additional noise compared with ambient conditions. However, within 2 min of noise cessation, ventilation rate showed complete recovery to levels equivalent to ambient-exposed control individuals. Care should be taken in generalizing these rapid-recovery results, as individuals might have accrued other costs during noise exposure and other species might show different recovery times. Nonetheless, our results from two different fish species provide tentative cause for optimism with respect to recovery following short-duration noise exposure, and suggest that considering periods following noise exposures could be important for mitigation and management decisions.