Antidepressant mechanisms of ketamine's action: NF-κB in the spotlight.

Ketamine recently approved for therapy of treatment-resistant depression shows a complex and not fully understood mechanism of action. Apart from its classical glutamatergic N-methyl-D-aspartate receptor antagonistic action, it is thought that anti-inflammatory properties of the drug are of clinical relevance due to the contribution of activated inflammatory mediators to the pathophysiology of depression and non-responsiveness of a group of patients to current antidepressant therapies. In a search of the mechanism underlying anti-inflammatory effects of ketamine, the nuclear factor kappa B transcription factor (NF-κB) has been proposed as a target for ketamine. The NF-κB forms precisely regulated protein signaling cascades enabling a rapid response to cellular stimuli. In the central nervous systems, NF-κB signaling appears to have pleiotropic but double-edged functions: on the one hand it participates in the regulation of processes that are crucial in the treatment of depression, such as neuroplasticity, neurogenesis or neuronal survival, on the other - in the activation of neuroinflammation and cell death. Ketamine has been found to reduce inflammation mediated by NF-κB, leading to decreased level of pro-inflammatory cytokines and other inflammatory or stress mediators. Therefore, this review presents recent data on the significance of the NF-κB cascade in the mechanism of ketamine's action and its future perspectives in designing new strategies for the treatment of depression.

Mechanisms of Cognitive Impairment in Depression. May Probiotics Help?

Depression is the major cause of disability globally. Apart from lowered mood and accompanying symptoms, it leads to cognitive impairment that altogether predicts disadvantaged social functioning. Reduced cognitive function in depression appears a bit neglected in the field of clinical and molecular psychiatry, while it is estimated to occur in two-thirds of depressed patients and persist in at least one third of remitted patients. This problem, therefore, requires elucidation at the biomolecular and system levels and calls for improvement in therapeutic approach. In this review study, we address the above-mentioned issues by discussing putative mechanisms of cognitive decline in depression: (1) increased oxidative stress and (2) inflammation, (3) disturbed hypothalamus-pituitary-adrenals axis, and (4) reduced monoamines functionality. Moreover, we acknowledge additional underpinnings of cognitive impairment in depressed elderly: (5) vascular-originated brain ischemia and (6) amyloid-beta plaque accumulation. Additionally, by reviewing molecular, pre-clinical and clinical evidence, we propose gut microbiota-targeted strategies as potential adjuvant therapeutics. The study provides a consolidated source of knowledge regarding mechanisms of cognitive impairment in depression and may path the way toward improved treatment options.

Association Between Consumption of Fermented Food and Food-Derived Prebiotics With Cognitive Performance, Depressive, and Anxiety Symptoms in Psychiatrically Healthy Medical Students Under Psychological Stress: A Prospective Cohort Study.

Background: Gut microbiota-based therapeutic strategies, such as probiotic and prebiotic preparations, may benefit mental health. However, commonly consumed fermented and prebiotic-containing foods have not been well-tested. The aim of the present study was to determine whether consumption of fermented food and food-derived prebiotics is associated with cognitive performance, depressive, and anxiety symptoms in psychiatrically healthy medical students under psychological stress. Methods: The study protocol with data analysis plan was prospectively registered. Food consumption was evaluated with a 7-day dietary record. Cognitive performance was modeled with academic examination performance in relation to subject knowledge. Pre-exam depressive and anxiety symptoms were assessed with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Results: In total, 372 medical students (22.7 ± 1.1 years of age, 66% female) completed the study. No relationship was observed between cognitive performance under stress and either fermented food (adjusted ß 0.02, 95% CI -0.07-0.11, p = 0.63) or food-derived prebiotics consumption (adjusted ß -0.00, 95% CI -0.09-0.09, p = 0.99). High intake of fermented food was associated with more severe depressive (adjusted ß 0.11, 95% CI 0.01-0.20, p = 0.032) and anxiety symptoms under stress (adjusted ß 0.13, 95% CI 0.04-0.22, p = 0.0065); however, no such link was observed for food-derived prebiotics (adjusted ß 0.03, 95% CI -0.07-0.13, p = 0.50 and -0.01, 95% CI -0.11-0.08, p = 0.83, for depression and anxiety, respectively). Conclusions: Under psychological stress in medical students, consumption of fermented food and food-derived prebiotics appears to be not associated with cognitive performance. High intake of fermented food, but not food-derived prebiotics, may be associated with severity of depressive and anxiety symptoms. The safety of fermented food in this regard therefore requires further clarification.

Health-, medication- and dietary supplement-related behaviors and beliefs relatively unchanged during the COVID-19 pandemic lockdown.

BACKGROUND: The lockdown imposed to counter the coronavirus disease 2019 (COVID-19) pandemic has evoked an unprecedented phenomenon that could affect health behaviors and beliefs. OBJECTIVE: To examine how medication-, dietary supplement- and health-related behaviors, beliefs and other psychological constructs changed in Polish online health service users during the COVID-19 pandemic lockdown. METHODS: A one-time online survey accessed through a health service website was completed before and during the pandemic lockdown by separate samples of respondents. The survey examined beliefs about medicines and dietary supplements, consumption of dietary supplements, trust and contact with their advertisements, sources of dietary supplement knowledge as well as perceived health, diet, physical activity and smoking, among other things. RESULTS: The study included 1560 participants. Most examined outcomes remained unchanged over COVID-19 pandemic lockdown. Beliefs that the dietary supplement quality is well controlled became significantly more pronounced during the lockdown (adjusted ratio of estimates 1.16, 95%CI 1.06-1.27, p = 0.001). Fewer people reported having contact with dietary supplement advertisements (adjusted odds ratio 0.59, 95%CI 0.43-0.83, p = 0.002). CONCLUSIONS: The results may help understand some health-related issues associated with COVID-19 pandemic lockdown and may be used to shape aspects of health-related policy.