Tetrahydrobiopterin deficiency in schizophrenia: Biochemical and clinical aspects.

It was reported that the levels of tetrahydrobiopterin (BH4) are reduced in schizophrenia. However, mechanisms of BH4 deficiency in schizophrenia had not been studied precisely. OBJECTIVE: the search of the association between BH4 deficiency in schizophrenia and a range of biochemical and clinical parameters for the evaluation of the possible mechanisms of BH4 loss and its role in the development of the symptoms. METHODS: 93 patients with schizophrenia and 60 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, cobalamin (B12), homocysteine, C-reactive protein (CRP), reduced glutathione (GSH) levels in the blood serum.Patients underwent standardized psychopathological examination. RESULTS: In patients, the levels of BH4 and folate were lower (p = 0.001 and p = 0.054, respectively), and the levels of homocysteine were higher (p = 0.012) compared to the control group. BH4 levels directly moderately correlated with folate (ρ = 0.43; p = 0.0029) and B12 levels (ρ = 0.43; p = 0.0020) and inversely moderately correlated with homocysteine levels (ρ = -0.54; p = 0.00015) in patients. Cluster analysis identified schizophrenia biotype characterized by a deficiency of BH4, folate, B12, and hyperhomocysteinemia. The clinical characteristics of this biotype were not specific. CRP and GSH were higher in patients compared to controls, but their association with serum BH4 was not confirmed.

[Validation of a DSM-5-based screening test using digital phenotyping in the Russian population]. / Validatsiya skriningovogo testa, osnovannogo na kriteriyakh DSM-5, metodom tsifrovogo fenotipirovaniya na rossiiskoi populyatsii.

OBJECTIVE: To evaluate the validity of a depression and anxiety screening test based on DSM-5 diagnostic criteria to identify cases of these conditions simultaneously assessed with the validated Hospital Anxiety and Depression Scale (HADS) in a population sample by digital phenotyping. MATERIAL AND METHODS: This cross-validation study included 5.116 respondents (mean age 36.9 (9.8)), of which 49.4% (2526) were women. The depression and anxiety screening test was done in electronic form and based on the DSM-5 diagnostic criteria for major depressive disorder and generalized anxiety disorder. The validated HADS scale was used as a standard test. The categories of depression (HADS-D) and anxiety (HADS-A) phenotypes were formed with a cutoff of ≥8 points and ≥11 points. The main parameters of the validity of the screening test were calculated, including accuracy (Ac), sensitivity (Sn) and specificity (Sp) with their 95% confidence intervals [CI]. RESULTS: The prevalence of current depression and anxiety according to the screening test was 7.8% (400) and 12.5% (639), respectively. The prevalence of lifetime depression was 25.9% (1327). For the HADS-D depression subscale with cut-offs of ≥11 and ≥8 points, the prevalence of depression was 3.4% (174) and 15% (766), respectively. For the HADS-A anxiety subscale with cut-offs of ≥11 and ≥8 points, the prevalence of anxiety was 8.9% (456) and 31.8% (1628), respectively. For HADS-D and HADS-A with a cutoff of ≥11 points, the parameters of current depression were Ac=92%, Sn=47% (CI 95% [39-54]), Sp=94% (CI 95% [93-94]), lifetime depression - Ac=75%, Sn=63% (CI 95% [56-70]), Sp=75% (CI 95% [74-77]) and current anxiety - Ac=88%, Sn=54% (CI 95% [50-59]) and Sp=92% (CI 95% [90-92]). For HADS-D and HADS-A with a cutoff of ≥8 points, the parameters of current depression were Ac=86%, Sn=30% (CI 95% [27-33]), Sp=96% (CI 95% [95-97]), lifetime depression - Ac=74%, Sn=51% (CI 95% [48-55]), Sp=75% 79% (CI 95% [77-80]) and current anxiety - Ac=75%, Sn=31% (CI 95% [29-33]), Sp=96% (95% CI [95-97]). CONCLUSION: The high Ac and Sp of this test allows it to be used for screening purposes to identify (but not exclude) cases of depression and anxiety in the population. However, further studies are needed to validate the screening test using a diagnostic interview with a physician.

[Anhedonia, depression, anxiety, and craving in opioid dependent patients stabilized on oral naltrexone or naltrexone implant]. / Angedoniia, depressiia, trevoga i vlechenie k upotrebleniiu narkotikov u patsientov s opioidnoi zavisimost'iu pri kursovom lechenii peroral'noi ili implantiruemoi formoi naltreksona.

AIM: To assess the relationship between long-term naltrexone treatment and anxiety, depression and craving in opioid dependent individuals. MATERIAL AND METHODS: Opioid dependent patients (n=306) were enrolled in a three cell (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month trial comparing extended release implantable naltrexone with oral naltrexone and placebo (oral and implant). Monthly assessments of affective responses used a Visual Analog Scale for opioid craving, the Beck Depression Inventory, Spielberger Anxiety Inventory, and the Ferguson and Chapman Anhedonia Scales. Between-group outcomes were analyzed using mixed model analysis of variance (Mixed ANOVA) and repeated measures and the post hoc Tukey test. RESULTS AND CONCLUSION: Anhedonia, depression, anxiety, and craving for opiates were elevated at baseline but gradually reduced to normal within the first 1-2 months for patients who remained in treatment and did not relapse. There were no significant between-group differences prior to treatment dropout as well as between those who relapsed and who continued on naltrexone. CONCLUSION: These data do not support concerns that naltrexone treatment of opioid dependence precipitates anhedonia, depression, anxiety or craving for opiates.

Meta-analysis: Problems with Russian Publications.

BACKGROUND: Meta-analysis is a powerful tool to identify Evidence Based medical technologies (interventions) for use in every day practice. Meta-analysis uses statistical approaches to combine results from multiple studies in an effort to increase power (over individual studies), improve estimates of the size of the effect and/or to resolve uncertainty when reports disagree. Meta-analysis is a quantitative, formal study design used to systematically assess previous research studies to derive conclusions from this research. Meta-analysis may provide more precise estimate of the effect of treatment or risk factor for a disease, or other outcomes, than any individual study contributing to the pooled analysis.We have quite a substantial number of Russian medical publications, but not so many Meta-Analyses published in Russian. Russian publications are cited in English language papers not so often. A total of 90% of clinical studies included in published Meta-Analyses incorporate only English language papers. International studies or papers with Russian co-authors are published in English language. OBJECTIVE: The main question is: what is the problem with inclusion of Russian medical publications in Meta-Analysis? RESULTS: The main reasons for this are the following: 1) It is difficult to find Russian papers, difficult to work with them and to work with Russian journals:a. There are single Russian Biomedical Journals, which are translated into English and are included in databases (PubMed, Scopus and other), despite the fact that all of them have English language abstracts.b. The majority the meta-analyses authors use in their work different citation management software such as the Mendeley, Reference Manager, ProCite, EndNote, and others. These citation management systems allow scientists to organize their own literature databases with internet searches and have adds-on for the Office programs what makes process of literature citation very convenient. The Internet sites of the majority of International Journals have built-in tools for saving citations to reference manager software. The majority of articles in Russian journals cannot be captured by citation management systems: they do not have special coding of articles descriptors.c. Some journals still have PDF files of the whole journal issue without dividing it into articles and do not provide any descriptors, making manual time-consuming input of information the only possibility. Moreover the context search of the article content is unavailable for search engines.2) The quality of research. This problem has been discussed for more than twenty years already. Still we have too many publications of poor quality of study design and statistical analysis. With the exception of pharmacological clinical tails, designed and supervised by international Pharma industry, many interventional studies, conducted in Russia, have methodological flaws inferring a high risk of bias:a. Absence of adequate control,b. No standard endpoints, duration of therapy and follow up,c. Absence of randomization and blinding,d. Low power of studies: sample sizes are calculated (if calculated at all) in such a way, that the main goal is to have as small sample size as possible. Very often statisticians have to solve the problem how to substantiate a small number of subjects, that sponsor could afford, instead of calculating the needed sample size to reach enough power.e. No standards of statistical analysis.f. Russian journals do not have standards for description and presentation of study results, in particular, results of statistical analysis (a reader even cannot see what is presented: standard deviation (SD) or standard error of the mean (SEM).We have a long standing experience in analysis of methodological and statistical quality of Russian biomedical publications and have found up to 80% publications with statistical and methodological errors and high risk of bias.In our practice, we had tried to perform two Meta-analyses for two local pharmaceutical products for prevention of stroke recurrence. For the first product, we did not found even two single Russian language studies suitable for the analysis (incomparable populations, different designs, endpoints, doses etc.). For the second product, only four studies had comparable populations and standard internationally approved scales for effectiveness analysis. However, the combinations of scales, the length of treatment and follow up differed widely, so that we could combine the results of only 2 or 3 studies for each end point. CONCLUSIONS: Russian researchers have to follow internationally recognised standards in study design, selection of endpoint, timelines and therapy regimens, data analysis and presentation of results. Russian journals need to develop consolidate rules for authors of clinical trials and epidemiological research of result reporting close to international standards. In this case the international Network EQUATOR (Enhancing the QUAlity and Transparency Of health Research http://www.equator-network.org/) is one to be taken into account. In addition, Russian Journals have to improve their online information for better interaction with search engines and citation managers.

Multimetric statistical analysis of behavior in mice selected for high and low levels of isolation-induced male aggression.

Behavioral observations as a matrix of probabilistic changes of postures and acts are multiple measurements that could introduce variability to statistical analysis. We propose the multimetric statistical algorithm that supplements the linear analysis of variance by pair correlation, factor and discriminant function analyses. Although these methods were utilized mostly in behavioral studies, the combined use in frame of one behavioral test was not done before. In present study statistical techniques were applied to analyze social behavior in Turku aggressive (TA) and Turku non-aggressive (TNA) mouse lines, bidirectional selected for offensive aggression towards an unknown male. Each statistical technique amplified new details of mouse behavioral profiles that give possibility to describe TA and TNA subjects in terms of Cloninger's model of personality. Also, it was identified that TA mice displayed fighting-biting aggression while TNA mice demonstrated immobile defensive strategy. Hypothetical discriminant formula was found for each mouse behavioral genotype that might be used to identify behavioral profile and line affiliation of unknown subjects.

Co-morbidity of infectious and addictive diseases in St. Petersburg and the Leningrad Region, Russia.

The Russian health care system is organized around specific diseases, with relatively little focus on integration across specialties to address co-morbidities. This organizational structure presents new challenges in the context of the recent epidemics of injection drug use (IDU) and HIV. This paper uses existing and new data to examine the prevalence of reported new cases of drug dependence (heroin) and HIV over time as well as associations between drug dependence and alcoholism, hepatitis B and C, and tuberculosis in the City of St. Petersburg and the Leningrad region. We found a sharp rise in reported cases of IDU beginning in 1991 and continuing until 2002/2003, followed by a sharp rise in newly reported cases of HIV. These rises were followed by a drop in new cases of HIV and drug addiction in 2002/2003 and a drop in the proportion of HIV-positive individuals with IDU as a risk factor. Infection with hepatitis B and C were common, especially among injection drug users (38 and 85%, respectively), but also in alcoholics (7 and 14%). Tuberculosis was more common in alcoholics (53%) than in persons with alcoholism and drug dependence (10%), or with drug dependence alone (4%). Though these data have many limitations, they clearly demonstrate that drug dependence and/or alcoholism, HIV, hepatitis, and tuberculosis frequently co-occur in St. Petersburg and the Leningrad Region. Prevention and treatment services across medical specialties should be integrated to address the wide range of issues that are associated with these co-morbidities.