[Evaluation of the therapeutic efficacy and safety of the selective anxiolytic afobazole in generalized anxiety disorder and adjustment disorders: Results of a multicenter randomized comparative study of diazepam]. / Otsenka terapevticheskoi effektivnosti i bezopasnosti selektivnogo anksiolitika afobazola pri generalizovannom trevozhnom rasstroistve i rasstroistvakh adaptatsii: rezul'taty mnogotsentrovogo randomizirovannogo sravnitel'nogo s diazepamom issledovaniya.

AIM: to summarize the previously published results of a multicenter randomized clinical research phase III study trial of afobazole (INN: fabomotizole) versus diazepam in the treatment of patients with generalized anxiety disorder (GAD) and adjustment disorders (AD). SUBJECTS AND METHODS: Five investigating centers included 150 patients aged 18 to 60 years (60 patients with GAD and 90 with AD) a simple structure of anxiety disorders without concurrent mental, neurological or somatic disorders. Patients were randomized to take afobazole (30 mg/day; n=100) or diazepam (30 mg/day; n=50) for 30 days. Prior to drug administration, patients susceptible to placebo were excluded according to the results of its 7-day use. Withdrawal syndrome was evaluated within 10 days after completion of active therapy. The primary efficacy endpoint was the change of Hamilton Anxiety Rating Scale (HAMA) total score. The scores of the Clinical Global Impression (CGI) Scale and the Sheehan Scale as secondary efficacy endpoints  were analyzed. Drug safety was evaluated by assessment of adverse events. RESULTS: Afobazole and diazepam caused a significant reduction of HAMA total score. In the afobazole group, the reduction of anxiety  exceeded that in the diazepam group (the difference in the total score changes was 2.93 [0.67; 5.19]; p=0,01).The proportion of patients with reduction of disease severity was 72% in the afobazole group and 58% in the diazepam group. After therapy completion, the proportion of patients with no or mild disorder in the afobazole group was significantly higher than that in the diazepam group (69 and 44%, respectively; χ2=12.46; p=0,014). There was a trend toward a higher subjective patient-rated estimate of the afobazole effect using the Sheehan scale. There were a total of 15 and 199 adverse events in the afobazole and diazepam groups, respectively. No manifestations of afobazole withdrawal syndrome were found. Diazepam withdrawal syndrome was observed in 34 (68%) patients. CONCLUSION: Afobazole is an effective and safe drug to treat patients with GAD and AD and non-inferior than diazepam in the treatment of these disorders, however it is superior in terms of several variables, including the safety profile.

[A case report of anti-NMDA receptor encephalitis with mental disturbances manifestation]. / Klinicheskoe nablyudenie anti-NMDA-retseptornogo entsefalita, protekayushchego s psikhicheskimi narusheniyami.

Presented clinical observation of anti-NMDA-receptor encephalitis, which was first described in 2007, is rare and to date has not been sufficiently studied. The disease often manifests with psychopathological symptoms and catatonia, so patients are transferred into a mental healthcare institution and often require intensive care and resuscitation, due to the development of life-threatening respiratory and hemodynamic disorders. Diagnosis is based on detection of autoantibodies to the NR1- and NR2 subunits of the glutamate NMDA receptor in blood serum and cerebrospinal fluid. Pathogenesis-based therapy includes the administration of glucocorticoids and intravenous immunoglobulins, plasmapheresis, as well as the introduction of monoclonal antibodies in also used, and in severe cases, cytostatics are prescribed. The widespread comorbidity of anti-NMDA receptor encephalitis with ovarian neoplasms in women (up to 60%) requires appropriate diagnosis and early removal of ovarian neoplasms when they are detected. With timely diagnosis and adequate treatment strategies, the outcome of this rare disorder is usually positive.

[Immunological and neuroanatomic markers of the clinical dynamics of MCI and pre-MCI]. / Immunologicheskie i neiroanatomicheskie markery dinamiki dodementnykh kognitivnykh rasstroistv pri neiroreabilitatsii.

OBJECTIVE: To study the relationship of the parameters of immunity and systemic inflammation with the structural magnetic resonance imaging (MRI) parameters in patients with mild cognitive impairment (MCI) and pre-MCI undergoing neurocognitive rehabilitation to search for candidate markers of its effectiveness. MATERIAL AND METHODS: The main group included 49 patients, aged ≥60 years, with MCI and pre-MCI with memory impairment, who underwent a course of neurorehabilitation for 5 weeks. The control group included 19 volunteers of similar age with a total MoCA score of ≥25, who did not have cognitive impairment and immuno-inflammatory disorders. The parameters of cellular and humoral immunity and markers of inflammation were studied, and structural MRI was performed. RESULTS: The content of activated natural killer cells (NK-cells) was increased in MCI and pre-MCI (0.63±0.12% vs. 0.22±0.07% in the control group, p=2.2·10-7). The level of immunoglobulin G (IgG) <12.5 g/l in patients with MCI and pre-MCI with the Montreal Cognitive Assessment Scale (MoCA) score <22 was associated with a decrease in the volume of the right nucleus accumbens (376±35 mm3 in patients with IgG <12.5 g/l (p=0.0013) and 480±44 mm3 at IgG <12.5 g/l, 480±44 mm3 in the control group), as well as with a decrease of the thickness and volume of a number of other cortical zones. A logistic regression model including the level of immunoglobulin G, NK cells, CD8+ NK cells and right amygdala volume was constructed to predict the number of MoCA scores 6 months after the course of rehabilitation (R2=0.57; p<1·10-5; standard error of estimate: 2.93). CONCLUSION: As a result of this work, the perspectives of assessing the immunological parameters in combination with socio-demographic data and morphometric changes of the brain as potential prognostic markers of the dynamics of cognitive impairment in patients with MCI and pre-MCI after neurorehabilitation has been shown.

[Changes in sleep patterns and the doom-scrolling (doom-surfing) phenomenon as modifiable risk factors for anxiety due to continuous stress of the COVID-19 pandemic]. / Izmeneniya rezhima sna i potreblenie informatsii s negativnym kontentom v internete («dumskrolling¼, «dumserfing¼) kak upravlyaemye faktory riska razvitiya trevogi v usloviyakh stressa pandemii COVID-19.

OBJECTIVE: To evaluate the modifiable daily behavior patterns associated with increased anxiety indicators in the general population in response to the COVID-19 pandemic. MATERIAL AND METHODS: The study examined the characteristics of the Russian population (n=7777) of the international multicenter project COMET-G. In particular, variables were targeted to describe deviations in the behavior of adults during the period of application of measures of social isolation in connection with the pandemic, and revealing a relationship with the total score on the Spielberger State Anxiety Scale (STAI-S). Among these variables, experts selected those that could potentially be subject to change in the short term, that is, act as manageable or modifiable risk factors for the development of anxiety. The selected variables were analyzed in a statistical PLS-model to identify indicators that make the most significant contribution to the increase in the total anxiety score. RESULTS: Our statistical model explained 48.4% of the variability in the STAI-S anxiety total scores related to changes in daily life habits. In particular, doom-scrolling/doom-surfing about the spread of the virus and the COVID-19 pandemic, changes in sleep patterns and usual daily life activities due to social isolation measures presented as factors significantly contributing to the increase of state anxiety. CONCLUSION: Given the manageable or modifiable risk factors that we have identified, public awareness and therapeutic recommendations, pointing to the need to (I) control the amount of time spent in the internet and monitor their internet-based content consumption, (II) regulate sleep-wake patterns, (III) maintain daily habits and household activities, may reduce the likelihood of developing anxiety disorders in the context of the impact of a global chronic stress due to the COVID-19 pandemic and associated social isolation measures.

[Effects of diet on the gut microbiome in patients with depression]. / Vliyanie diety na mikrobiom kishechnika u patsientov s depressiei.

OBJECTIVE: To investigate the effects of diet on the gut microbiota and to assess the relationship of these factors with depression. MATERIAL AND METHODS: Microorganisms that predominate in depressed patients were identified and associations of the identified organisms with the patients' diet were performed. Fourteen depressed patients and 14 healthy volunteers with the same socio-demographic parameters were included in the study. The Hamilton Depression Scale, Generalized Anxiety Disorder Questionnaire, and the Center for Epidemiologic Studies Questionnaire were used. RESULTS: Erysipelatoclostridium and Clostridium innocuum species were 11.3 and 14.4 times higher in depressed patients compared with healthy controls. Fusicatenibacter saccharivorans, Faecalibacterium prausnitzii and Roseburia faecis species, as well as members of the genus Roseburia were statistically significantly more abundant in the healthy volunteers group (6.5, 2.14, 8.75 and 5.2 times more frequently compared to patients). The presence of these microorganisms was correlated with dietary components. CONCLUSION: Our study revealed groups of microorganisms that differ in healthy volunteers and depressed patients. The association of these microorganisms with the diet was shown, which partially confirmed the influence of a «healthy diet¼ on the development of depressive disorders.

[Psychotic disorders in the veterans of local wars]. / Psikhoticheskie rasstroistva u veteranov lokal'nykh voin.

OBJECTIVE: To determine the frequency of the key psychopathological syndromes, the dynamics and comorbidity of schizophrenia and other psychoses in Russian veterans of local wars receiving hospital treatment. MATERIAL AND METHODS: The study included 685 patients of a psychiatric department of a military hospital, including 264 veterans of the local wars (the main group), 296 people (career military servicemen and retirees), who do not take part in combat actions (the first comparison group) and 125 people matched for the middle age and the age distribution curve with the main group (the second comparison group). RESULTS AND CONCLUSION: The frequency of psychoses appeared to be slightly less in veterans (7.2%) compared to patients of comparison groups (14.5% and 8.8%, respectively). In all groups, most patients were diagnosed with schizophrenia (ICD-10 F20): 3.8% in the main group, 4.4% in the first comparison group and 4.0% in the second comparison group. Other acute and chronic psychotic disorders (F22-F23) were diagnosed in 0.8, 5.4 and 3.2% patients, respectively. Organic delusion disorders were diagnosed in 1.5% patients of the main group, 3.7% patients of the first comparison group and were not detected in the second comparison group. Comorbidity of posttraumatic stress disorder (PTSD) and psychosis was about 2% in the main group in whole and 26.3% in those with schizophrenia and other delusional disorders. The degree of incidence of symptoms of PTSD in veterans diagnosed with psychosis was significantly less than their frequency among all veterans (20% and 46.9%, respectively). Military stress factors do not influence the development of hallucinations and delusions in the main group. In the majority of veterans, psychotic symptoms manifested for the first time after stopping combat stress, the subsequent development and recurrence of psychotic symptoms happened regardless of the influence of combat stress factors.

Impact of COVID-19 pandemic on anxiety, depression and distress - online survey results amid the pandemic in Russia.

Background: In 2020, the COVID-19 pandemic evoked a variety of research into the virus and its effects on mental health. A variety of mental health and psychological problems have been reported: stress, anxiety, depressive symptoms, insomnia, denial, stigma, anger and fear. Objectives: To assess the level of anxiety, depression and distress in the general population during the lockdown in Russia and to reveal factors associated with distress. Methods: An online survey was carried out from 22-27 April 2020 (the fourth week of lockdown) among the general population (mostly Moscow residents). The survey questions covered general information about people's social and demographic characteristics, experience of COVID-19, health condition (physical and mental), attitudes and views on the pandemic, and the need for psychological support. The survey included the Hospital Anxiety and Depression Scale (HADS) and evaluation of the preceding week's subjective distress level using a visual numeric scale (from 0 to 10). We also asked respondents to specify the causes of distress, adopted from the WHO information sheet relating to the major psychological challenges of the COVID-19 pandemic. Results: In total, 352 responses were collected (men = 74, women = 278; age (M ± SD) = 36.81 ± 11.36 y.o.).Most respondents (n = 225, 63.92%) did not have any personal experience of the coronavirus infection. Normal levels of anxiety and depression scores were prevalent in the sample. Higher than normal levels of HADS anxiety/depression ( 7 scores) were observed in 105 (29.83%) and 59 (16.76%) respondents, respectively; mean (95% CI)scores for HADS anxiety/depression were 6.23 [5.77, 6.68] /4.65 [4.22, 5.08] (women) and 4.20 [3.32, 5.09] /3.46[2.63, 4.29] (men), respectively.The leading causes of distress were: 1) the risk of financial problems in the future (n = 267, 76.3%); 2) violation of plans and the disruption to normal life (n = 235, 67.1%; and n = 240, 68.6%, respectively); 3) the health of elderly or chronically diseased relatives (n = 205, 58.6%) and 4) being in self-isolation (n = 186, 53.1%). Conclusion: The level of anxiety and depression during the COVID-19 pandemic in the study sample did not exceed the norm for the population in non-pandemic conditions. Our assessment of distress levels captured existing emotional problems, and distress levels were found to be connected with the reported need for psychological support.

[Results of a clinical study of a new anxiolytic, a blocker of central cholecystokinin receptors]. / Rezul'taty klinicheskogo issledovaniia novogo anksiolitika, blokatora tsentral'nykh kholetsistokininovykh retseptorov.

AIM: To evaluate anxiolytic action of GB-115, a low-affinity blocker of central cholecystokinin receptors, used in tablets in a dose of 1 mg for the treatment of patients with anxiety disorders in order to determine effective dose, safety, tolerability and efficacy in clinical settings. MATERIAL AND METHODS: The study included 31 patients (22 women, 9 men) diagnosed with generalized anxiety disorder (GAD, F41.1 according to ICD-10), aged from 22 to 53 years. The duration of treatment was 21 days. The Hamilton Anxiety Rating scale, Psychopathologic symptoms severity evaluation scale (PSSES), Spilberger State-Anxiety Inventory, Multidimensional Fatigue Inventory (MFI), Clinical Global Impression scale (CGI), computerized battery for evaluation of cognitive functions ('NS-Psychotest') were used. RESULTS AND CONCLUSION: The effective dose of GB-115 was determined at 6 mg per day. Drug action is characterized by fast onset of anxiolytic effect with stimulating properties and beneficial effect on sleep disturbances and autonomic symptoms. GB-115 treatment was associated with favorable changes in attention parameters, reaction time and overall performance. In contrast to first-line drugs for GAD treatment (SSRIs and SNRIs), GB-115 does not induce initial overactivation, anxiety and sleep disturbances. GB-115 is safe and has a good tolerability.