Dominika Berent

Vascular endothelial growth factor gene (VEGFA) polymorphisms may serve as prognostic factors for recurrent depressive disorder development.

Recurrent depressive disorder (rDD) is a multifactorial disease. Vascular endothelial growth factor (VEGF) is one of the factors that have been suggested to play a role in the etiology and/or development of this disease. Limited information related to the role of VEGFA gene polymorphism in depressive disorder is available. The aim of the study was to analyze the association between VEGFA gene polymorphisms (+405G/C; rs2010963, +936C/T; rs 3025039), VEGFA gene expression, and its serum protein levels in rDD in the Caucasian population. In the current study, 268 patients and 200 healthy controls of the Caucasian origin were involved. Genotyping and gene expression were performed using polymerase chain reaction (PCR)-based methods. Enzyme-linked immunosorbent assay (ELISA) was used for detection of circulating serum VEGF levels. The distribution of VEGFA polymorphism +405G/C differed significantly between rDD patients and healthy subjects. The results of this study indicated that the C allele and CC genotype of VEGFA are risk factors for rDD. Haplotypes CC and TG are the important factors for depression development. Further, VEGFA mRNA expression and VEGF levels were higher in rDD patients than in controls. The VEGFA gene polymorphism may serve as a prognostic factor for rDD development. Our study showed higher levels of both VEGFA mRNA in the peripheral blood cells and serum VEGF in patients diagnosed with rDD than in healthy controls. The obtained results suggest VEGF and the gene encoding the molecule play a role in the etiology of the disease and should be further investigated.

Vascular endothelial growth factor receptor 2 gene (KDR) polymorphisms and expression levels in depressive disorder.

Recent research findings suggest that vascular endothelial growth factor (VEGF) participates in the development of depressive disorder. VEGF is involved in neurogenesis and neuroprotection processes, mediated by vascular endothelial growth factor receptor 2 (VEGFR2). VEGFR2 also plays a role in angiogenesis, a process related to neurogenesis and other biological processes. We examined VEGFR2 (KDR) gene polymorphism, mRNA expression levels, as well as VEGFR2 protein levels in 268 patients diagnosed with a recurrent depressive disorder (rDD) using the ICD-10 criteria, and in 200 healthy controls. Genotyping and gene expression level analysis was performed using polymerase chain reaction (PCR)-based methods. An Enzyme-Linked Immunosorbent Assay (ELISA) was used for measurement of KDR protein levels. Our study found that distribution of KDR polymorphism +1416T/A differs significantly in patients with rDD when compared to healthy subjects, while A allele and AA genotype are risk factors for rDD. KDR mRNA and protein expression are higher in patients with rDD. We also observed a significant association between the -271A/G variant and gene and protein levels. Our study is the first to demonstrate that the KDR gene may serve as a novel genetic marker that could participate in the etiology of rDD. This new pathway may play a role in the inflammatory pathophysiology of depression.

SSTR4, childhood adversity, self-efficacy and suicide risk in alcoholics

Abstract Background Patients with alcohol dependence (AD) are known to develop poor social skills, to report a higher number of adverse childhood experiences (ACEs) and to attempt suicide more frequently than the general population. The background for the association between ACEs and a higher risk of suicide still remains understudied. SSTR4 rs2567608 is a functional polymorphism of the gene for somatostatin receptor subtype 4, predominantly found in the CA1 hippocampus area and involved in memory formation. We hypothesize that the functional polymorphism SSTR4 rs2567608, general self-efficacy, and adverse childhood experiences influence the risk of suicide attempt in patients with AD. Methodology 176 patients with AD and 127 healthy controls were interviewed regarding 13 categories of ACEs and assessed with the General Self-Efficacy Scale. Genotyping for the SSTR4 rs2567608 polymorphism was performed according to the manufacturer’s standard PCR protocol. Results Patients with AD and the controls did not differ significantly according to the SSTR4 rs2567608 genotype and allele frequencies. Lower general self-efficacy, higher number of ACEs, and the SSTR4 rs2567608 TT genotype increased the risk of suicide attempt in patients with AD, and it persisted significant only in male patients with AD. Conclusions Our study supports previous findings on ACEs and general self-efficacy association with a risk for suicide. Additionally, we suggest that patients with AD of the SSTR4 rs2567608 TT genotype may be more vulnerable to ACEs and at a higher risk of suicide attempt.

The Heidenhain variant of Creutzfeldt-Jakob disease – two patients initially misdiagnosed with dissociative disorder

Summary Background: The Heidenhain variant of sporadic Creutzfeldt-Jakob disease is characterized by prominent visual complaints that last in isolation for some weeks and are often misdiagnosed until rapid cognitive decline with suggestive neurological symptoms appear. The treatment is only symptomatic, but correct diagnosis established at the time of visual symptom isolation helps to avoid needless diagnostic or treatment procedures and may give time to patients and their families to prepare for the worst. Case Report: We report on 2 cases based on available medical documentation. Written informed consents for publication were obtained from the patients’ families after the patients’ deaths. We report on the cases of 2 men with sporadic Creutzfeldt-Jakob disease first manifested with visual symptoms in which ophthalmological and neurological background was excluded and misdiagnoses of dissociative disorder were made. Further diagnosis in a psychiatry ward suggested probable sporadic Creutzfeldt-Jakob disease, which was confirmed at postmortem examination. Conclusions: Although visual symptoms are listed in the World Health Organization diagnostic criteria for sporadic Creutzfeldt-Jakob disease, initial symptoms can be vague enough to be misdiagnosed even by neurologists. We conclude that in visual disturbances in which ophthalmological and neurological background is at first excluded, a differential diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) should be considered. In patients with a diagnosis of visual dissociative disturbances, the Heidenhain variant of sCJD should be considered in the differential diagnosis. Repeated EEG in patients with visual disturbances of unknown cause can detect abnormalities suggestive of sporadic Creutzfeldt-Jakob disease.

Childhood adversities are not a predictors of SSTR4met in alcoholics

Abstract Background Genome methylation may modulate synaptic plasticity, being a potential background for mental disorder. Adverse childhood experiences (ACEs), known to be frequently reported by patients with alcohol dependence (AD), have been proposed as one of environmental inequities influencing DNA methylation. The study is aiming 1.To assess a promoter region methylation in gene for somatostatin receptor subtype-4 (SSTR4), a receptor for somatostatin, a neurotransmitter engaged in neuroplasticity and memory formation, in patients with AD; 2. To verify if SSTR4 promoter methylation is associated with ACEs and other selected environmental factors. Methodology: 176 patients with AD and 127 healthy controls were interviewed regarding 13 categories of ACEs; a structured self-reported questionnaire - to measure the sociodemographic and clinical characteristics; a module of Catalogue of Healthy Behavior – to assess nutritional health habits; the Alcohol Use Disorders Identification Test – to assess drinking severity. The SSTR4 promoter region methylation status was performed via methylation-specific PCR, and the genotyping for the SSTR4 rs2567608 functional polymorphism - according to the manufacturer’s standard PCR protocol. Results SSTR4 promoter region was found methylated in 21.6% patients with AD and 2.3% controls. None of following characteristics: current age, gender, term and kind of labor, 13 categories of childhood trauma, diet, alcohol drinking severity, age at alcohol drinking initiation, age at onset of problem drinking, cigarette smoking, and SSTR4 rs2567608 was a significant predictor for SSTR4 promoter region methylation. Conclusions SSTR4 promoter region methylation in here studied participants may be either inherited epigenetic modification or secondary, but not to here assessed variables.

Difficulties in identifying emotional states in patients treated for depressive disorders compared to patients with selected somatic diseases

Summary Background: Dysfunction in cognitive and affective domains limiting access to mental states in the self and impairing identification of emotions is defined as alexithymia. It leads to the inability to realize and recognize feelings, to use language to describe them, and to differentiate between emotions and bodily symptoms. Alexithymia is considered to be a stable personality feature, which along with other personality factors predispose to numerous mental and somatic disorders. Material/Methods: Our test group included 30 patients diagnosed with the following mood disorders: depressive episode and recurrent depressive disorder. The first comparison group consisted of 30 patients treated for coronary heart disease, heart failure, and heart rhythm disorders, some of them with coexisting hypertension and history of myocardial infarction. The second comparison group was composed of 22 outpatients diagnosed with hepatitis C. The Bermond Vorst Alexithymia Questionnaire-(BVAQ) was used in the study. Results: Statistically significant differences were found in most of the dimensions, thus resulting in overall differences in level of alexithymia between groups. There was no difference between groups only in poverty of imagination and concrete thinking. Respondent age and duration of illness coexisted with higher levels of alexithymia (total score) and selected alexithymic dimensions mainly in the group of patients with hepatitis, and also for the entire population. Conclusions: Respondents with a diagnosis of mood disorders are characterized by greater deficits in identify ing and naming their own emotional states as compared to patients with a diagnosis of cardiac disease or viral hepatitis.