A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study.

The kynurenine pathway (KP) and inflammation are substantial in depression pathogenesis. Although there is a crosstalk between the KP, inflammation, and neurotrophic factors, few studies examine these topics together. Novel medications may be developed by clarifying dysregulations related to inflammation, KP, and neurotrophic factors in treatment-resistant depression (TRD). We aimed to evaluate the serum levels of KP metabolites, proinflammatory biomarkers, and brain-derived neurotrophic factor (BDNF) in healthy controls (HC) and the patients with TRD whose followed up with three different treatments. Moreover, the effect of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on biomarkers was investigated. Study groups comprised a total of 30 unipolar TRD patients consisting of three separate patient groups (ECT = 8, rTMS = 10, pharmacotherapy = 12), and 9 HC. The decision to administer only pharmacotherapy or ECT/rTMS besides pharmacotherapy was given independently of this research by psychiatrists. Blood samples and symptom scores were obtained three times for patients. At baseline, quinolinic acid (QUIN) was higher in the patients with TRD compared to HC, whereas picolinic acid (PIC), PIC/QUIN, and PIC/3-hydroxykynurenine were lower. Baseline interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were higher in nonresponders and non-remitters. ECT had an acute effect on cytokines. In the rTMS group, tumor necrosis factor-α (TNF-α) decreased in time. PIC, QUIN, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) enzyme may play a role in TRD pathogenesis, and have diagnostic potential. rTMS and ECT have modulatory effects on low-grade inflammation seen in TRD. Baseline inflammation severity is predictive in terms of response and remission in depression.

Behavioral and Neurodevelopmental Effects of Early Interventions in Adult Wistar Rats.

INTRODUCTION: Interventions performed in the early period of life are associated with cognitive and behavioral changes in adulthood. The effects of interventions such as exposure to an early stressful life event or environmental enrichment on cognitive and behavioral development are studied. The aim of this study is to develop a new intervention method, to investigate the effects of early interventions on social interaction, memory anxiety levels and NR2B levels in prefrontal and hippocampus in adulthood. The hypothesis of the study is that exposure to the ambivalent mother will affect the behavioral performance of rats at least as much as one hour apart from the mother in the adult period and cause changes in the prefrontal cortex and hippocampus in the NR2B levels. METHOD: In the study, the Wistar rats were divided into four groups as control group (12), group that remained 15 minutes apart from mother (Mild Stress) (12), group that remained 60 minutes apart from mother (Severe Stress) (14) and ambivalent mother group (13). In adulthood, the social interaction test, elevated plus maze and new object recognition test performances of rats were evaluated. ELISA method was used to evaluate the effect of interventions on the prefrontal cortex and hippocampus NMDA R2B levels. RESULTS: The important findings of the study were that in the new object recognition test, separation from the mother did not affect the recognition memory regardless of gender, while the short-term recognition memory of the females of the ambivalent mothers' group was better than the females in the other groups and the long-term memory performance of the mild stress groups men was better than the man in the other groups. In addition, in the social interaction test, the males of the ambivalent group and the mild stress group showed more aggressive behavior. It was determined that the prefrontal cortex NR2B level was higher in the mild stress and ambivalent mother group compared to the severe stress group, and NR2B level was increased in all intervention groups compared to the control group. CONCLUSION: In contrast to the hypothesis, the results of this study support that the ambivalent mother's group rats are not more adversely affected than the severe group rats and that the model created may be an environmental enrichment model rather than an early stressful life event exposure.