Impact on the Risk and Severity of Childhood Onset Schizophrenia of Schizophrenia Risk Genetic Variants at the DRD2 and ZNF804A Loci.

The study explored whether schizophrenia risk alleles of the DRD2 rs2514218 and ZNF804A rs1344706 polymorphisms also influenced the risk and severity of childhood-onset schizophrenia (COS) and differentiated it from autism spectrum disorders (ASD). We compared 75 children with COS to 75 children with ASD, 150 patients with adult-onset schizophrenia and 150 healthy individuals. Frequency of the DRD2 T-allele, assumed to be protective against schizophrenia overall, was higher in COS compared to adult-onset schizophrenia and healthy controls. The risk allele A of ZNF804A was associated with greater severity of negative symptoms in COS. The latter result is consistent with the involvement of ZNF804A in the development of severe forms of schizophrenia. The findings regarding DRD2 suggest that the same genetic variants may play different roles in schizophrenia with childhood and adult onset. This warrants further research, since D2 receptor blockade is a general pharmacodynamic property of antipsychotics.

Oxidized cell-free DNA as a stress-signaling factor activating the chronic inflammatory process in patients with autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASD) are known to be associated with an inflammatory process related to immune system dysfunction. This study's aim was to investigate the role of cell-free DNA in chronic inflammatory process in ASD patients. METHODS: The study included 133 ASD patients and 27 healthy controls. Sixty-two ASD patients were demonstrated to have mild-to-moderate disease severity (group I) and 71 individuals to have severe ASD (group II). Plasma cell-free (cf) DNA characteristics, plasma cytokine concentrations, expression of the genes for NFкB1 transcription factor and pro-inflammatory cytokines TNFα, IL-1ß and IL-8 in peripheral blood lymphocytes (PBL) of ASD patients, and unaffected controls were investigated. Additionally, in vitro experiments with oxidized DNA supplementation to PBL cultures derived from ASD patients and healthy controls were performed. RESULTS: The data indicates that ASD patients have demonstrated increased cfDNA concentration in their circulation. cfDNA of patients with severe ASD has been characterized by a high abundance of oxidative modification. Furthermore, ASD patients of both groups have shown elevated plasma cytokine (IL-1ß, IL-8, IL-17A) levels and heightened expression of genes for NFкB1 nuclear factor and pro-inflammatory cytokines TNFα, IL-1ß, and IL-8 in PBL. In vitro experiments have shown that NF-κB/cytokine mRNA expression profiles of ASD patient PBL treated with oxidized DNA fragments were significantly different from those of healthy controls. CONCLUSIONS: It may be proposed that oxidized cfDNA plays a role of stress-signaling factor activating the chronic inflammatory process in patients with ASD.

A method for reclassifying cause of death in cases categorized as "event of undetermined intent".

BACKGROUND: We present a method for reclassifying external causes of death categorized as "event of undetermined intent" (EUIs) into non-transport accidents, suicides, or homicides. In nations like Russia and the UK the absolute number of EUIs is large, the EUI death rate is high, or EUIs comprise a non-trivial proportion of all deaths due to external causes. Overuse of this category may result in (1) substantially underestimating the mortality rate of deaths due to specific external causes and (2) threats to the validity of studies of the patterns and causes of external deaths and of evaluations of the impact of interventions meant to reduce them. METHODS: We employ available characteristics about the deceased and the event to estimate the most likely cause of death using multinomial logistic regression. We use the set of known non-transport accidents, suicides, and homicides to calculate an mlogit-based linear score and an estimated classification probability (ECP). This ECP is applied to EUIs, with varying levels of minimal classification probability. We also present an optional second step that employs a population-level adjustment to reclassify deaths that remain undetermined (the proportion of which varies based on the minimal classification probability). We illustrate our method by applying it to Russia. Between 2000 and 2011, 521,000 Russian deaths (15 % percent of all deaths from external causes) were categorized as EUIs. We used data from anonymized micro-data on the ~3 million deaths from external causes. Our reclassification model used 10 decedent and event characteristics from the computerized death records. RESULTS: Results show that during this period about 14 % of non-transport accidents, 13 % of suicides, and 33 % of homicides were officially categorized as EUIs. Our findings also suggest that 2011 levels of non-transport accidents and suicides would have been about 24 % higher and of homicide about 82 % higher than that reported by official vital statistics data. CONCLUSIONS: Overuse of the external cause of death classification "event of undetermined intent" may indicate questionable quality of mortality data on external causes of death. This can have wide-ranging implications for families, medical professionals, the justice system, researchers, and policymakers. With our classification probability set as equal to or higher than 0.75, we were able to reclassify about two-thirds of EUI deaths in our sample. Our optional additional step allowed us to redistribute the remaining unclassified EUIs. Our method can be applied to data from any nation or sub-national population in which the EUI category is employed.

Ribosomal DNA Abundance in the Patient's Genome as a Feasible Marker in Differential Diagnostics of Autism and Childhood-Onset Schizophrenia.

Introduction: Differential diagnostics of early-onset schizophrenia and autism spectrum disorders (ASD) are a problem of child psychiatry. The prognosis and relevant treatment are to a large degree determined by the correctness of diagnosis. We found earlier that leucocyte DNA of adult schizophrenia patients contained significantly larger copy numbers of ribosomal repeats (rDNA) coding for rRNA, than DNA of mentally healthy controls. Aim: To compare the contents of ribosomal repeats in the leucocyte DNA of children with schizophrenia, children with ASD, and healthy age-matched controls to estimate the possibility of using this genetic trait in the differential diagnostics of the two types of disorders. Patients and methods: Blood samples of patients with infantile autism (A­F84.0 according to ICD-10, N = 75) and with childhood-onset schizophrenia (SZ­F20.8 according to ICD-10, N = 43) were obtained from the Child Psychiatry Department of the Mental Health Research Center. The healthy control blood samples (HC, N = 86) were taken from the Research Centre for Medical Genetics collection. The recruitment of cases was based on the clinical psychopathologic approach. DNA was extracted from blood leukocytes with organic solvents. Nonradioactive quantitative hybridization technique was applied for determining the abundance of ribosomal repeats in the genomes. Statistical processing was performed using StatPlus, Statgraphics and MedCalc. Findings: DNA derived from SZ cases contained 565 ± 163 rDNA copies, which is significantly (p < 10−6) higher than the rDNA content in ASD cases (405 ± 109 copies) and controls (403 ± 86 copies). The HC and A groups did not differ by rDNA copy number (p > 0.4). The genetic trait "rDNA copy number in patient's genome" can potentially be applied as an additional marker in differential diagnostics of childhood-onset schizophrenia and autism spectrum disorders.

Feasibility of Virtual Tablet-Based Group Exercise Among Older Adults in Siberia: Findings From Two Pilot Trials.

BACKGROUND: Regular physical activity has a positive effect on physical health, well-being, and life satisfaction of older adults. However, engaging in regular physical activity can be challenging for the elderly population because of reduced mobility, low motivation, or lack of the proper infrastructures in their communities. OBJECTIVE: The objective of this paper was to study the feasibility of home-based online group training-under different group cohesion settings-and its effects on adherence and well-being among Russian older adults. We focused particularly on the technology usability and usage and on the adherence to the training (in light of premeasures of social support, enjoyment of physical activity, and leg muscle strength). As a secondary objective, we also explored the effects of the technology-supported intervention on subjective well-being and loneliness. METHODS: Two pilot trials were carried out exploring two different group cohesion settings (weak cohesion and strong cohesion) in the period from 2015 to 2016 in Tomsk, Russian Federation. A total of 44 older adults (59-83 years) participated in the two pilots and followed a strength and balance training program (Otago) for 8 weeks with the help of a tablet-based virtual gym app. Participants in each pilot were assigned to an interaction condition, representing the online group exercising, and an individual condition, representing a home-based individual training. Both conditions featured persuasion strategies but differed in the ability to socialize and train together. RESULTS: Both interaction and individual groups reported a high usability of the technology. Trainees showed a high level of technology acceptance and, particularly, a high score in intention to future use (4.2-5.0 on a 5-point Likert scale). Private texting (short service message [SMS]) was used more than public texting, and the strong cohesion condition resulted in more messages per user. Joint participations to training sessions (copresence) were higher for the social group with higher cohesion. The overall adherence to the training was 74% (SD 27%). Higher levels of social support at baseline were associated with higher adherence in the low cohesion condition (F1,18=5.23, P=.03), whereas in the high cohesion, such association was not found. Overall improvement in the satisfaction with life score was observed between pre and post measures (F1,31=5.85, P=.02), but no decrease in loneliness. CONCLUSIONS: Online group exercising was proven feasible among healthy independently living older adults in Russia. The pilots suggest that a physical training performed in a virtual environment positively affect the life satisfaction of the trainees, but it does not provide support for a decrease in loneliness. High cohesion groups are preferable for group exercising, especially to mitigate effects of low social support on adherence. Further research in motivating group interactions in training settings is needed.

Exploring predictors of life satisfaction and happiness among Siberian older adults living in Tomsk Region.

Despite the growing interest in studying factors affecting subjective well-being of older adults, little research has been conducted on vast territory of Siberia (Russia) with large population. To address this lack of evidence, we explored the relationship between subjective well-being and social aspects (social and emotional support, social network, and social activities), living conditions (standards of living and residence area), self-reported health, and demographic characteristics in older adults living in Tomsk Region, Siberia. Subjective well-being was measured by life satisfaction and happiness (each measured with one 11-point question). Sample included 489 community-dwelling respondents, aged 65 or older. We found that mean life satisfaction and happiness reported by our respondents were lower than those of European countries. Higher quality of social interaction, better standards of living, and being satisfied with own health were associated with higher life satisfaction and happiness. This study provides original data on a region barely investigated and suggests that Siberian older adults receive strong benefits from social support and from social network and that similar factors are related to subjective well-being both in Siberian and Eastern European older adults. Future studies should further explore the relationship between different kinds of social support (e.g., psychological vs. material support) and subjective well-being in different Siberian ethnic groups or regions.