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Background: Depression in patients with schizophrenia worsens the course of the disease by increasing the risk of suicide, by complicating the clinical picture of the disorder, and by reducing the quality of the social functioning; its treatment is difficult, since monotherapy, even when involving modern antipsychotics, does not always prove successful. While the prescription of additional antidepressants (ADs) can improve the likelihood of a better outcome, the effectiveness of such augmentation in many cases is yet to be proven. Therefore, it is still important that one weighs the effectiveness of various combinations between most of the known ADs and some second-generation antipsychotic (SGA) in the treatment of depression that occurs at different stages of schizophrenia. In previous studies, the use of vortioxetine as an adjunct to an antipsychotic yielded a reduction in negative symptoms, a clinically significant improvement in cognitive functions that differed from its antidepressant effect, and good tolerability, which affects how committed to treatment a patient remains., Aim: To study the changes that occur over time in the clinical manifestations of depression, negative and cognitive impairment, as well as the social adequacy of patients receiving a combination therapy with second-generation antipsychotics and vortioxetine, which were prescribed in real clinical practice at doses approved in the Russian Federation., Methods: We performed a comparative analysis of the changes in depression symptoms and negative symptoms, cognitive impairment, as well as function of 78 patients with severe manifestations of depression at the stage of exacerbation reduction and subsequent remission of paranoid schizophrenia. Combination treatment with SGA and vortioxetine was used in 39 patients, and 39 patients who had similar clinical manifestations received just SGA. During the observation period, the mental disorder severity and depression symptom severity were assessed 3 times (before the start of treatment, after three months, and after six months) using the Clinical Global Impression (CGI) scale and Calgary Depression Scale for Schizophrenia (CDSS), respectively; patients were also assessed using the Negative Symptoms Assessment-5 (NSA-5) scale, Perceived Deficits Questionnaire-20 items (PDQ-20) scale, and Personal and Social Performance (PSP) scale., Results: According to the ANOVA results, by the end of the observation period, patients, regardless of their therapeutic group, showed a statistically significant decrease in the level of depression on the CDSS scale, the severity of negative symptoms on the NSA-5 scale, cognitive symptoms on the PDQ-20 scale, as well as an improvement in personality and society, judging by the increase in the total PSP scores. There were also significant differences between the compared main (SGA + vortioxetine) and control (SGA) groups in terms of the changes in the total score on the CDSS and PSP scales. An interesting aspect of the changes in the clinical scores was a noticeable improvement in the SGA + vortioxetine group after 3 months of treatment, in the absence of a similar improvement in the control group, and the achievement of approximately the same scores in both groups after 6 months. In particular, there were significant differences between the SGA + vortioxetine and SGA groups in terms of the mean CDSS ( p 0.001), NSA-5 ( p =0.003), PDQ-20 ( p 0.001), and PSP ( p =0.004) scores after 3 months. Analysis of the time before early withdrawal from the study showed that significantly more patients in the SGA + vortioxetine group completed the study program ( n =27, 69.23%) compared with the SGA group ( n =13, 33.33%) ( 2 =14.618, df=1, p 0.001, log-rank test. The mean survival time in the SGA group was significantly ( p 0.001) less and amounted to 101.436 days (95% CI: 81.518121.354), and in the SGA + vortioxetine group it amounted to 161.744 days (147.981175.506). The relative risk of full study completion in the vortioxetine + SGA group compared with that in SGA was 3.618 (1.8716.994)., Conclusion: The addition of vortioxetine to the SGA therapy accelerates the reduction of the depression symptoms that occur at the stage of psychosis regression and early remission, contributes to the accelerated reduction in negative symptoms, positively affects the subjective assessment of cognitive impairment severity, and has a significant positive effect on the level of psychosocial functioning., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023, Reznik A.M., Syunyakov T.S., Mudrak A.V., Zakharov N.B., Popova Z.B., Khoroshilova A.N., Khurbatova I.G., Saifulina A.M., Eliseenko A.M., Matvievskaya T.K., Khannanova A.N.)

Introduction: Schizophrenia, although a debilitating mental illness, greatly affects individuals' physical health as well. One of the leading somatic comorbidities associated with schizophrenia is cardiovascular disease, which has been estimated to be one of the leading causes of excess mortality in patients diagnosed with schizophrenia. Although the shared susceptibility to schizophrenia and cardiovascular disease is well established, the mechanisms linking these two disorders are not well understood. Genetic studies have hinted toward shared lipid metabolism abnormalities co-occurring in the two disorders, while lipid compounds have emerged as prognostic markers for cardiovascular disease. In particular, three ceramide species in the blood plasma, Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1), have been robustly linked to the latter disorder., Aim: We aimed to assess the differences in abundances of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in the blood plasma of schizophrenia patients compared to healthy controls., Methods: We measured the abundances of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) in a cohort of 82 patients with schizophrenia and 138 controls without a psychiatric diagnosis and validated the results using an independent cohort of 26 patients with schizophrenia, 55 control individuals, and 19 patients experiencing a first psychotic episode., Results: We found significant alterations for all three ceramide species Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and a particularly strong difference in concentrations between psychiatric patients and controls for the ceramide species Cer(d18:1/18:0)., Conclusions: The alteration of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) levels in the blood plasma might be a manifestation of metabolic abnormalities common to both schizophrenia and cardiovascular disease., Competing Interests: Conflict of interests: The authors declare no conflict of interest., (© Authors, 2021.)

Background: Cariprazine is a new piperazine derivative atypical antipsychotic, like aripiprazole and brexpiprazole. It has been approved for treating schizophrenia in many countries and has recently been included on the List of Essential Medicines in Russia. Unlike most other atypical antipsychotics, it shows high in vivo occupancy of dopamine D2 and D3 receptors at clinically relevant doses. In animal models, cariprazine has demonstrated dopamine D3 receptor-dependent pro-cognitive and anti-anhedonic effects, suggesting its potential for treating negative symptoms. This review summarizes the efficacy of cariprazine in the treatment of negative symptoms of schizophrenia., Methods: A literature search of databases covering international and Russian journals, for articles published between 1st January 2010 and 1st June 2020., Results: Cariprazine demonstrated at least comparable efficacy in the treatment of schizophrenia symptoms to active comparators including risperidone, olanzapine or aripiprazole. The drug has a good safety profile. It appeared to be associated with a lower risk of metabolic syndromes and most extrapyramidal symptoms. The positive effect of cariprazine on the negative symptoms of schizophrenia may be associated with the elimination of secondary negative symptoms. However, of all the atypical antipsychotics to date, only cariprazine has a convincingly, methodologically robust proven advantage over risperidone in eliminating the predominant negative symptoms of schizophrenia. Yet only four studies have investigated the effect of cariprazine on the negative symptoms of schizophrenia. There is a lack of research into its direct impact on emotional-volitional disorders, anhedonia, cognitive symptoms and personality changes. However, there is evidence to suggest cariprazine is effective in treatment-resistant cases, but this requires further confirmation., Conclusion: Cariprazine is an effective and well-tolerated agent for the treatment of schizophrenia and may be effective in cases where other antipsychotics have failed. Cariprazine has been shown to have a positive effect on negative symptoms. Further studies are needed to collect more data on long-term treatment of schizophrenia and especially negative symptoms., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020, Reznik A.M., Arbuzov A.L., Murin S.P., Pavlichenko A.V.)

Depression is a serious mental disorder that affects more than 300 million people worldwide. Due to the lack of effective treatment methods, the pathogenesis of depression is necessary to study in order to understand its development and find new therapies. The review describes the main mechanisms of depression, including the monoamine hypothesis, impairment of the hipotalamic-pituitary-adrenal axis, decreased production of neurotropic factors, and neuroinflammation. Genetic correlations, gene polymorphisms, and epigenetic mechanisms are also considered. Common and different features of the etiology are analyzed for depression and depressive conditions associated with other pathologies (schizophrenia, Parkinson disease, and Alzheimer's disease). Modern experimental methods used to investigate the molecular mechanisms of depressive conditions are described with a focus on gene knockouts in laboratory animals and the CRISPR/Cas technology. Consideration is given to optogenetic and chemogenetic methods and analyses of genetic polymorphisms and their combinations. The data may provide for a better integral understanding of the modern ideas about the pathogenesis of depression as an isolated or comorbid disorder and the prospects in studying the mechanisms of depressive conditions.

Objective: An analysis of the efficacy and safety of additional therapy of excitement with the injectable form of alimemazine during exacerbations of schizophrenia with psychomotor agitation, impulsivity, including dangerous behavior, irritability, conflict, hostility, aggressiveness, anxiety, sleep disturbances (insomnia)., Material and Methods: Thirty patients, aged 18 to 65 years, with a diagnosis of «paranoid schizophrenia», established in accordance with the ICD-10 criteria, were studied. The patients received treatment with a second-generation antipsychotic and alimemazine (intramuscular injection solution) in daily dose from 25 mg to 150 mg during no more than 9 days. The patients were assessed with psychometric scales (PANSS, ABS, HARS and VAS) four times during the observation period., Results and Conclusion: During therapy with a combination of second-generation antipsychotics and alimemazine solution for intramuscular injection, a reliable ( p <0.001) reduction in the severity of psychotic symptoms assessed with PANSS was achieved by 8-9 days (the average total score decreased by 30% relative to the initial level) that indicated the improvement in all manifestations of schizophrenia exacerbation. A decrease of 34.8% ( p =0.007) in the risk of aggression (PANSS points S1-S3) was established. The level of excitation on the agitation scale (ABS) decreased by 3.6% ( p <0.001). In 50% of patients, manifestations of anxiety disappeared, and the average HARS score decreased by 2.2 times compared with the initial level ( p <0.001). Almost half of the patients noted the normalization of sleep, and the average value of sleep disturbance on a visual analogue scale decreased threefold compared with the initial level ( p <0.001). The observed adverse events were moderate or mild. Alimemazine shows the highest efficacy in the treatment of anxiety arousal in patients with schizophrenia with affective-delusional attacks.

Objective: To determine the network connections between clinical, cognitive, speech and oculographic parameters in patients with schizophrenia., Material and Methods: The study included 104 patients with schizophrenia and schizophrenia spectrum disorders and 70 healthy subjects. Clinical assessment of the patients was performed using a number of scales: PANSS, CDSS, YMRS, SAS and BAS. Basic cognitive functions were assessed by BACS. Eye movements were recorded using the SMI RED-500 non-invasive eye tracking system. Several experimental paradigms were used - free viewing of animal images with subsequent description of these images, performing progressive saccades in the experimental Go/NoGo scheme, and performing anti-saccades., Results: The severity of clinical symptoms, cognitive impairments, oculomotor parameters and characteristics of speech structure of written speech are largely independent, although not completely isolated from each other. Cognitive and oculomotor parameters have the largest number of connections. In this case, the results of cognitive tests are the central element of the «network» that connects other groups., Conclusion: Further development of the approach should be aimed at studying the influence of node changes on the structure of the network that would potentially allows the identification of the most effective points of application of therapeutic and rehabilitation programs.

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.

The review is devoted to the analysis of the current state of pharmacogenetic research and their use in psychiatric practice. The main genes responsible for the pharmacodynamics and pharmacokinetics of drugs used in psychiatry are listed. Foreign pharmacogenetic clinical recommendations and progress on their implementation in medical practice in various countries of Europe and the USA are analyzed. The need to create Russian clinical guidelines on pharmacogenomics to improve the effectiveness of patient care and to implement a personalized approach to therapy is discussed.

Schizophrenia is a disease with a complex non-Mendelian inheritance mechanism in most cases involving the combined action of a large number of genes. Identifying of genomic variations associated with schizophrenia endophenotypes has a great potential. This review describes genetic markers of the disease, current methods of their analysis, including genome-wide association study (GWAS). Certain genes with mutations that increase the risk of schizophrenia are described. Functional polymorphisms with phenotypic expression, which are significantly associated with clinical manifestation of schizophrenia, can serve as useful genetic markers. The authors highlight that currently there are no certain susceptibility genes. Further global research and search for markers in different population groups are needed.

A method of optimisation of new extractants structure using the desirable function has been developed. Earlier the desirable function has been proposed by Harrington (Ind Qual Control 21: 494-498, 1965) for the optimisation of processes with several response functions. The developed method of optimisation of new extractants structure has been used for construction of phenolic type extractants (PTE) (a class of N-(2-hydroxy-5-nonylbenzil)-dialkylamines). It has been offered to use the charge on the nitrogen atom, the heat of dissociation of phenolic group, the logarithm of distribution factor of extractant between water and octanol (computed data) and maximum permissible concentration of extractants in aqueous phase (MPC) of the o-replaced phenols (the literary data) as the controllable parameters, defining efficiency of extractants for molecular design of PTE. During optimisation of extractants structure the quantity of alkyl substitutes at nitrogen atom, the carbon atoms number in these substitutes and the electronegative substitutes in o-position to phenolic group have been varied. As the result of the molecular design, the optimal structure of PTE found is N-(2,3-dihydroxy-5-nonylbenzil)-didecylamine, which perfectly meets the requirements to industrial extractants.

Glutamate neurotransmission has been considered as one of pathogenetic factors of schizophrenia though all antipsychotics widely used in modern psychiatric practice are dopamine antagonists. LY2140023 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors with antipsychotic effect. In the present study, we have assessed clinical efficacy of LY2140023 in patients with schizophrenia compared to the control group receiving olanzapine in a randomized double-blind placebo-controlled trial. The statistically significant reduction of positive and negative symptoms measured with the PANSS (p<0.001) was observed for both antipsychotics at week 4 of treatment compared to placebo. The treatment with LY2140023 was safe and well-tolerated; treated patients did not differ from the placebo group by hyperprolactinemia and extrapyramidal symptoms, and weight gain. The results suggest that the agonist for 2/3 (mGlu2/3) receptors has antipsychotic properties and provides a new, alternative to dopamine agonists, method for pharmacotherapy of schizophrenia.

An aim of the study was to find stress reduction methods preferred by combatants. One hundred and nineteen servicemen who do contract military service in the North Caucasus were questioned. More than a half of them named the support of colleges in arms. The awareness of importance of their aid was correlated with the duration and intensity of experiencing combat stress. Every fifth combatant chose individual combat experience out of all methods. The longer was duration of service in a combat zone, the more increased the subjective significance of personal experience. More than a third of combatants considered alcohol and drugs as effective means for stress reduction. Veterans, who iteratively did military service in military zones and had been wounded, and direct participants of combats named these means even more often. Among those examinees who noted alcohol as an effective mean for stress reduction, 26.6% noted also drugs and 20%--sedatives. The author suggests that the interest of combatants in alcohol and any drug that has an effect on the mental state indicates the higher risk of taking other psychoactive drugs.

Using the method of nameless interrogation, there were investigated 119 service-men, served by contract on Northern Caucasus. 76,5% of investigated persons recognized different types of distress. The most often, features of psychic ill-being were signed by persons, obtained different wounds. Among typical symptoms of acute stress reactions the most often were the evidences of "invasion" (21%), tension (13,5%), lowed attune (14,3%). It's necessary attend, that involuntary revising and high irritation with an aptitude of evidence of anger often worried participants of warfare. Tension, backward, worried, in general, the persons, not yet participated in warfare. Persons, participated in warfare for the first time,signed the psychic tension rather rare. Lowed attune were signed very rare for the persons, served in the area of contraterrorist actions for the second time and having a big battle experience. During the evaluation of comorbidity of different symptoms of stress disease were signed, that the most often with another types of symptoms are conjoined: high irritation, sense of weariness, sense of fault and lowed attune. These symptoms can serve as markers of tendency to syndrome-making and, that's why, require special attention of psychologist and psychiatrist of military unit of medical service.

The article presents the review of neurophysiological and neuro-morphological researches of combat posttraumatic stress disorder. Also in the article presented data about the existence by the veterans, suffered by combat posttraumatic stress disorder, a regular dysfunction of hypothalamus-pituitary-paranephric system, approving by excessive allowance ruffling ofcortisol, tending the activation neuro-trasmitteric systems. These changes conjoin with predominance of sympaticotony and of increased psycho and physiological inflammability in response to cues, associated with real or imaginable danger. Methods of neurovisulisation show the existence of changes in visceral brain, prefrontal and sense-motorical zone of cerebrum, corresponded to stress signals. The article presents the discuss of cause-and-effects conditions between the morphological changes in central nervous system, influence of stress-factors and advance of disease.

Schizophrenia is a chronic, complex and heterogeneous mental disorder, with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain. These pathological features manifest behaviorally as positive symptoms (including hallucinations, delusions and thought disorder), negative symptoms (such as social withdrawal, apathy and emotional blunting) and other psychopathological symptoms (such as psychomotor retardation, lack of insight, poor attention and impulse control). Altered glutamate neurotransmission has for decades been linked to schizophrenia, but all commonly prescribed antipsychotics act on dopamine receptors. LY404039 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. With data from rodents, we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine. To clinically test this mechanism, an oral prodrug of LY404039 (LY2140023) was evaluated in schizophrenic patients with olanzapine as an active control in a randomized, three-armed, double-blind, placebo-controlled study. Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P < 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.

peculiarities of battle posttraumatic stress disorder (PTSD) and personal grounds to criminal aggression of 174 veterans of local wars and armed conflicts. It's shown, that the highest probability of accomplishment of socially dangerous actions is at the term of first 3 years after the influence of stress battle factors. More over different PTSD symptoms. These traits concerned to the following spheres: emotional, cognitive and sphere of values. Among pathologic traits of character, especially clear were shown explosive treats of character, hostility, predominatation of negative emotions, hardly one-sided type of judgments, changes in structure of leading motives and values. Sometimes the scale of moral estimations had double character: "our-strange", "friend-enemy". The highest risk of progress of acute stress reactions with aggressive behavior takes place on condition of disphoria-anxious version of PTSD, which is maximally characterized by person's changes, having sthenic character.

The article is devoted to the actual problem, i.e. the stress-provoked suicidal behavior in servicemen. Basing on the investigation of 195 servicemen committed the suicidal actions the significance of suicidal behavior prerequisites such as constitutional peculiarities and unfavorable conditions in social environment was determined. General personal features typical of such persons are described. It was established that among them there is a number of quite specific stigmas. It was determined that the presence of contradictions between the marked aggressive radical and impossibility of its realization lead to autoagression. The significance of this problem for the theory and practice of general and forensic psychiatry was revealed.

Depressive state in cancer patients is known to meet the criteria of mild depressive episode (F33.0) according to ICD-10. In the earlier stages of the disease and after successful treatment, depressive symptoms are usually combined with anxiety and obsessive fear, moderate appearances of ideator and motor inhibition, with permanent presence of asthenic symptoms. Once the disease is getting severer and the treatment is less successful, asthenia acquires hyposthenic features, with symptoms of apathy and dysphoria being attached. Cypramil was shown to be an effective medication in the treatment of depression in patients with malignant tumors of gastric-intestinal tract. The most efficient was the treatment conducted on the earlier stages of the cancer process and in cases of successful surgery and chemotherapy, in combination of depression with anxiety, anxious hypochondria, asthenia. Antidepressants must be used together with psychotherapy.

Thirty one patients, aged 23-48 years, with ICD-10 diagnosis of psychogenic neurotic depression (F32.0 and F32.1), were studied. According to antidepressants used, the patients were divided into 2 groups, of which the test one included 19 patients treated by cipramil (20-40 mg/day) and the comparative one consisted of 12 patients treated with amitriptilin (25-50 mg/day). The treatment duration was 28 days. The patient's state was evaluated, using clinical approach and instrumental methods, i.e. Hamilton depression scale, before treatment and on 14th and 28th days. After cipramil treatment, 14 patients out of 19 exhibited an improvement, with 5 revealing neurotic symptoms compensation. However, 5 patients proved to be resistant to the medication. In amitriptilin treatment, complete depression reduction was found only in 1 patient, with pronounced improvement being shown in 8 out of 12 patients. No changes in the patient's state were revealed for 3 cases. Cipramil treatment was not accompanied with any side effects.

A mathematical model was developed to predict the distortions in the measured expiratory CO2 concentration time profile caused by catheter sampling systems. Parameters considered included the expiratory flow and concentration profiles, the sample flow rate, the sample tube dimensions and the sample cell volume. Unless care is taken in choosing the parameters of a catheter sampling system, particularly in the presence of low expiratory flow rates and short expiratory times, the CO2 concentration profile may be severely distorted. In worst case situations end tidal CO2 plateaux may not be recognized or alternately artifactual plateaux may be produced. Sample flow rate and sample cell volume are the most important parameters while distortion within the sample tube itself is relatively less important.