BDNF rs962369 Is Associated with Major Depressive Disorder.

This study enrolled 291 patients diagnosed with depression and schizophrenia (F32, F33, and F20 according to ICD-10) and 227 ethnicity-matched control subjects. We analyzed the distribution of BDNF rs6265 and BDNF rs962369 genotypes, finding no significant associations between these and schizophrenia. We revealed a significant increase in the risk of single-episode major depression disorder (MDD) for rs962369 minor allele homozygotes (CC vs. TT+TC), an association that persisted after adjusting for age and sex (OR 3.47; 95% CI 1.36-8.85; p = 0.009). Furthermore, rs962369 genotype was significantly associated with an increased risk of recurrent MDD in a log-additive model (OR per C-allele 1.65; 95% CI 1.11-2.45; p = 0.013). A comparative analysis between MDD subtypes and between MDD subtypes and schizophrenia showed no significant differences for BDNF rs6265. Notably, the frequency of minor allele C of BDNF rs962369 varied across subgroups, with the highest frequency in patients with recurrent MDD (0.32) and the lowest in schizophrenia patients (0.20). The presence of genotypes with at least one minor allele C was significantly higher in the recurrent MDD patient group compared to the schizophrenia group. In conclusion, the BDNF rs962369 variant was associated with MDD but not with schizophrenia.

Association Study of BDNF, SLC6A4, and FTO Genetic Variants with Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The present study aimed to evaluate the association of SLC6A4 (5-HTTLPR), FTO (rs9939609), and BDNF (rs6265, rs962369) polymorphisms with schizophrenia spectrum disorders in Slovak patients. We analyzed the genotypes of 150 patients with schizophrenia, schizotypal, and delusional disorders and compared them with genotypes from 178 healthy volunteers. We have found a marginally protective effect of LS + SS genotypes of 5-HTTLPR variant of the serotonin transporter SLC6A4 gene against the development of schizophrenia spectrum disorders, but the result failed to remain significant after Bonferroni correction. Similarly, we have not proven any significant association between other selected genetic variants and schizophrenia and related disorders. Studies including a higher number of subjects are warranted to reliably confirm the presence or absence of the studied associations.

Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

Evaluation of Neuropsychiatric Complications in Hospitalized COVID-19 Patients.

BACKGROUND: Previous research has shown that COVID-19 patients are at risk of developing mental disorders. Limited number of studies about psychiatric and neuropsychiatric presentations in hospitalized COVID-19 patients is currently available. SUBJECTS AND METHODS: Subjects were 172 patients diagnosed with COVID-19 and requiring inpatient care, hospitalized at reprofiled clinics of the university hospital. The study aimed to quantify psychiatric symptoms, and determine correlations with agitation, BMI, mortality, and other variables (age, sex, oxygen therapy, intubation, etc.). RESULTS: Mental disorders due to known physiological conditions were of highest prevalence (n=105, 62.9%), followed by anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (n=34, 20.4%), and dementia (n=21, 12.6%) in COVID-19 patients. Depressive disorders (n=13, 7.9%), alcohol related disorders associated with withdrawal symptoms (n=10, 6%), and schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (n=4, 2.4%) were less common. Patients diagnosed with mental disorders due to known physiological conditions were significantly older compared to patients with other diagnoses. The depression was observed more commonly in patients treated with high-flow nasal oxygen (HFNO), and patients disconnected from invasive mechanical ventilation (IMV). Mixed anxiety-depressive symptoms were observed in 23.8% of the patients (n=41), and they were more prevalent in younger patients compared to patients without anxiety-depressive symptoms. Agitated patients were significantly older than non-agitated patients. No connection was observed between the occurrence of agitation and treatment with HFNO, nor in case of patients disconnected from IMV; however, the relationship between agitation and death proved to be statistically significant (OR = 5.9, 95% CI 2.33-15.29). CONCLUSION: Analysis of psychiatric and neuropsychiatric presentations in COVID-19 patients and their correlation with multiple variables provides a better understanding of the effect of infection on mental health, and brings forth a necessity of transdisciplinary approach in handling COVID-19 patients.

Analysis of Motives and Factors Connected to Suicidal Behavior in Patients Hospitalized in a Psychiatric Department.

(1) Background: This study aimed to investigate the motives and factors connected to suicidal behavior in 121 hospitalized patients with intentional self-harm (diagnosis X 60-81 according to the ICD-10); (2) Methods: Suicidal behavior of the patient was assessed from data obtained by psychiatric examinations and by the Columbia Suicide Severity Rating Scale. Analysis of data to identify the patients' reason and motives behind suicidal behavior in a group of patients with a suicide attempt (SA, n = 80) and patients with Non-Suicidal Self-Injurious Behavior (NSSIB, n = 41) was carried out; (3) Results: Results showed that patients with affective disorder have a 19-times higher rate of SA against other diagnoses. Patients with personality disorders have a 32-times higher rate of NSSIB than patients with other diagnoses. Living alone and the absence of social support increased the likelihood of SA. Qualitative data analysis of patients' statements showed different themes in the justification of motives for suicidal behavior between SA and NSSIB cases. Significant differences were shown for non-communicated reasons, loneliness, social problems, extortion, and distress; (4) Conclusions: The evaluation of patients' verbal statements by qualitative analysis during the psychiatric examination should be considered in clinical practice. It should be considered to include self-poisoning in the criteria of the Non-suicidal Self-Injury diagnostic categories.

Evaluation of 5-HTTLPR (insertion/deletion) and BDNF (rs6265) genetic variations in the Slovakian individuals suffering from affective disorders.

The pathophysiology of affective disorders (AD), including depressive disorders (DD) and anxiety disorders (ANXD), is still unclear. To understand risk factors of the disorders, we evaluated genetic variations of the serotonin reuptake transporter (5-HTTLPR, ins/del) and the brain-derived neurotrophic factor (BDNF, rs6265) in Slovak patients suffering from AD. After genotyping we observed a significantly increased frequency of LS and LL genotypes (5-HTTLPR) in individuals diagnosed with AD compared to controls (OR = 1.99, 95% CI = 1.21-3.27, p = 0.006). There was also a significant relationship between TT (BDNF) genotype and the risk of AD in males (OR = 5.93, 95% CI = 1.42-27.07, p = 0.011). In gene-gene analysis, the LL or LS (5-HTTLPR) and CT or TT (BDNF) genotype combinations had a risk-enhancing effect on AD susceptibility (mainly ANXD in males), while SS (5-HTTLPR) and TT (BDNF) combination had a protective effect on AD risk (mainly ANXD). However, larger prospective studies are needed to confirm our findings.

Hydrolytic Cleavage Products of Globin Adducts in Urine as Possible Biomarkers of Cumulative Dose: Proof of Concept Using Styrene Oxide as a Model Adduct-Forming Compound.

A new experimental model was designed to study the fate of globin adducts with styrene 7,8-oxide (SO), a metabolic intermediate of styrene and a model electrophilic compound. Rat erythrocytes were incubated with SO at 7 or 22 °C. Levels of specific amino acid adducts in globin were determined by LC/MS analysis of the globin hydrolysate, and erythrocytes with known adduct content were administered intravenously to recipient rats. The course of adduct elimination from the rat blood was measured over the following 50 days. In the erythrocytes incubated at 22 °C, a rapid decline in the adduct levels on the first day post-transfusion followed by a slow phase of elimination was observed. In contrast, the adduct elimination in erythrocytes incubated at 7 °C was nearly linear, copying elimination of intact erythrocytes. In the urine of recipient rats, regioisomeric SO adducts at cysteine, valine, lysine, and histidine in the form of amino acid adducts and/or their acetylated metabolites as well as SO-dipeptide adducts were identified by LC/MS supported by synthesized reference standards. S-(2-Hydroxy-1-phenylethyl)cysteine and S-(2-hydroxy-2-phenylethyl)cysteine, the most abundant globin adducts, were excreted predominantly in the form of the corresponding urinary mercapturic acids (HPEMAs). Massive elimination of HPEMAs via urine occurred within the first day from the erythrocytes incubated at both 7 and 22 °C. However, erythrocytes incubated at 7 °C also showed a slow second phase of elimination such that HPEMAs were detected in urine up to 50 days post-transfusion. These results indicate for the first time that globin adducts can be cleaved in vivo to modified amino acids and dipeptides. The cleavage products and/or their predictable metabolites are excreted in urine over the whole life span of erythrocytes. Some of the urinary adducts may represent a new type of noninvasive biomarker for exposure to adduct-forming chemicals.