Association between genetic variants and depression in a Romanian cohort.

Major depressive disorder (MDD) is beyond doubt a common, disabling, and costly condition. MDD associates hypothalamic-pituitary-adrenal (HPA) axis alterations. We sought to investigate two candidate variants which could have a role in the genetic susceptibility for stress or corticoid-induced MDD: glucocorticoid receptor (GR) - nuclear receptor subfamily 3 group C member 1 (NR3C1) rs41423247 and brain-derived neurotrophic factor rs6265 BDNF:c.442G>A Val66Met. We enrolled 82 Romanian subjects, 1:2 male to female ratio, 53.54±8.98 years old, diagnosed with an episode of major depression at the Clinical Neuropsychiatry Hospital in Craiova, Romania, and 286 healthy controls, 34.28±16.34 years old. All subjects were genotyped using specific ThermoFisher Scientific assays on a ViiA™ 7 real-time polymerase chain reaction (PCR) system. The impact of certain genetic variants may be ethnic-specific. In our Romanian cohort, rs41423247 NR3C1:c.1184+646C>G has a minor allele frequency of 29.2%, and rs6265 BDNF:c.442G>A of 22.2%. Neither reached significance in our study, under any of the association models - dominant, recessive, or allelic. Interpretation of our negative findings requires caution: literature provides arguably more evidence for the association between the analyzed polymorphisms; our study has sample size challenges, from which refined phenotyping limitations derive.

The Influence of Covid-19 Infection on Neurocognitive Disorders.

Neurocognitive disorders are a group of disorders characterized by an impaired cognition which has not been present since birth or very early life and represents a decline from a previous attained level of functioning. The case we studied is M.E., a 62 years female, married, from rural area, working as a tailor, without any psychiatric history. She develops psychiatric symptoms during Covid-19 infection and treatment, in November 2020. The patient has been admitted in psychiatric care, in that time, for about one month, for a persistent confusion state during and after this event. These symptoms diminish the patient's level of functioning and seemed to be related with the Covid-19 infection or treatment. Psychological investigation underlines a MMSE 14, severe impairment in attention, short-term and long-term memory. CT evaluation presents normal relation except a moderate general atrophy, according with patient's age. Differential diagnosis will be discussed. The treatment has proven its effectiveness, the patient regaining her ability to orientate, could do housework, good improvement in attention and short-term memory. We emphasize that there is correlation between the Covid-19 infection and confusive state and delirium in patients, as a comorbidity, followed in many cases by chronic progressive neurocognitive disorder, especially in elderly.

TSH and T4 Levels in a Cohort of Depressive Patients.

Depression is a significant contributor to the overall burden of disease on a global scale. Thyroid hormones thyroxine (T4) and triiodothyronine (T3) have been shown to play a critical role in the development and normal function of the brain. It has been suggested that dysregulation of thyroid function could be associated with depression, especially hypothyroidism, but not all studies support this hypothesis. We enrolled a cohort of 96 subjects with major depressive disorder and tested TSH and FT4 levels for 80 of them in order to assess the status of the hypothalamic-pituitary-thyroid axis (HPT). We found 7 cases (8.75% of the tested) of subclinical hyperthyroidism and 1 case (1.25%) of overt hyperthyroidism. While we did not find supporting evidence for association between TSH and FT4 levels and depression, our findings question whether screening depressive patients for HPT axis anomalies could be clinically relevant, if anything, in a regional context.

Circulating Cortisol in a Cohort of Depressive Patients.

It has long been suspected that the hypothalamic pituitary adrenal (HPA) axis plays a role in the pathophysiology of depression. Whether this association exists or not, and if it does, the degree of its significance, remain highly disputed. The issue is further complicated as no consensus currently exists on cortisol sampling timepoints or methods. Our study aimed to evaluate HPA functionality by evaluating plasma cortisol levels in a cohort of patients diagnosed with Major Depressive Disorder (MDD). We enrolled 96 subjects admitted for a major depressive episode and tested serum cortisol levels for 80 of them. We found that only 15 (12%) had values that were outside the normal reference range, with 14 of these being below the normal threshold. We also interviewed the patients and obtained self-reported information regarding previous depressive episodes, treatment administration, anxiety, suicidal ideas and suicidal gestures. Our study did not find a significant association between cortisol levels and the number of previous depressive episodes, the presence of feelings of anxiety, suicidal ideas or suicidal gestures. While our cohort did not find an association between cortisol levels and depression other authors have reported significantly different results and as such, more research is needed in order to establish or infirm this hypothesis.

Present Status and Future Challenges of New Therapeutic Targets in Preclinical Models of Stroke in Aged Animals with/without Comorbidities.

The aging process, comorbidities, and age-associated diseases are closely dependent on each other. Cerebral ischemia impacts a wide range of systems in an age-dependent manner. However, the aging process has many facets which are influenced by the genetic background and epigenetic or environmental factors, which can explain why some people age differently than others. Therefore, there is an urgent need to identify age-related changes in body functions or structures that increase the risk for stroke and which are associated with a poor outcome. Multimodal imaging, electrophysiology, cell biology, proteomics, and transcriptomics, offer a useful approach to link structural and functional changes in the aging brain, with or without comorbidities, to post-stroke rehabilitation. This can help us to improve our knowledge about senescence firstly, and in this context, aids in elucidating the pathophysiology of age-related diseases that allows us to develop therapeutic strategies or prevent diseases. These processes, including potential therapeutical interventions, need to be studied first in relevant preclinical models using aged animals, with and without comorbidities. Therefore, preclinical research on ischemic stroke should consider age as the most important risk factor for cerebral ischemia. Furthermore, the identification of effective therapeutic strategies, corroborated with successful translational studies, will have a dramatic impact on the lives of millions of people with cerebrovascular diseases.

Cellular and Molecular Mechanisms Underlying Non-Pharmaceutical Ischemic Stroke Therapy in Aged Subjects.

The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H2S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory. CONCLUSION: animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects.

Autophagy in aging and disease.

Autophagy is a catabolic degradation system used to destroy and recycle the unnecessary or damaged components of a cell. Autophagy is present at a basal level in all mammals and is regulated by some conditions, such as oxidative stress, starvation or hypoxia. In aged tissues, increased but also decreased expression of autophagy-specific proteins, Beclin 1, LC3, Atg5 and Atg7 has been reported. Likewise, it could be shown that the lifespan of yeast, nematodes and flies is prolonged by pharmacologically stimulated autophagy using exogenous administered spermidine. Autophagy is potentially implicated in acute lung injury and sepsis, two main causes of morbidity and mortality worldwide. Finally, a quite recent study supports the hypothesis that autophagy might be useful in vascular disease prevention by stimulating cholesterol efflux, which leads to inhibition of necrotic core formation and lipid accumulation. Since autophagy is also implicated in neuro-protection, in Alzheimer's and Huntington's disease animal models and many others normal and pathological states, including immunity, diabetes mellitus, different kind of tumors, colorectal cancer, different inflammations, lung diseases, neurodegenerative diseases, autophagy is of interest to many biomedical researchers.