Vol 4, No 1 (2023)
- Year: 2023
- Published: 31.03.2023
- Articles: 5
- URL: https://consortium-psy.com/jour/issue/view/12
- DOI: https://doi.org/10.17816/CP.202341
RESEARCH
Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain
Abstract
BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorder’s pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions.
AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions.
METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold.
RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p <0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p <0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways.
CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research.
5-16
Treatment of Depression with Vortioxetine and Second Generation Antipsychotics During the Period of Remission Formation in Schizophrenia (Interim Data Analysis)
Abstract
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%) (χ2 =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: 81.518–121.354), and in the SGA + vortioxetine group it amounted to 161.744 days (147.981–175.506). The relative risk of full study completion in the vortioxetine + SGA group compared with that in SGA was 3.618 (1.871–6.994).
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.
18-36
Efficacy of a Relaxation Scenario in Virtual Reality for the Comorbid Symptoms of Anxiety and Asthenia in a General Hospital Setting: A Pilot Comparative Randomized Open-Label Study
Abstract
BACKGROUND: Patients in general hospitals often display concomitant signs of mental maladjustment: low mood, anxiety, apathy, asthenia, all of which can have a negative impact on the course of the underlying disease and the recovery process. One of the non-pharmacological approaches that has gained wider acceptance in medical practice in recent years is the use of procedures based on virtual reality.
AIM: Assess the efficacy of the new domestic, virtual reality application Flow as relates to symptoms of anxiety and asthenia in patients undergoing inpatient treatment.
METHODS: The study was open-label and had a comparison group; the patients were assigned to the experimental or control group using a randomization table. The patients were assessed using the Spielberger State Anxiety Inventory; the Fatigue Symptom Rating Scale; the Well-being, Activity, Mood questionnaire; the Depression Anxiety Stress Scale; and the Clinical Global Impression Scale. Physical parameters were measured before and after each virtual reality session. The obtained data were statistically processed.
RESULTS: The study involved 60 patients. In 40 patients, the treatment program included a course of five daily relaxation sessions in virtual reality; the control group consisted of 20 patients, who were treated in accordance with the usual practice of the institution. The addition of virtual reality sessions to the standard treatment course yielded significant advantage in terms of affective symptoms reduction in patients both after a single session and as a result of undergoing the full course, and several days after its completion. The patients in the experimental group also showed a significant decrease in blood pressure after the sessions, and this was most pronounced in individuals who initially had elevated and high blood pressure.
CONCLUSION: The use of relaxation program courses in the virtual reality application Flow is an effective and promising means of non-pharmacological care for non-psychiatric inpatients showing symptoms of anxiety, apathy, depressive mood, as well as hypertension.
38-51
REVIEW
Modern Approaches to the Diagnosis of Cognitive Impairment and Alzheimer’s Disease: A Narrative Literature Review
Abstract
BACKGROUND: The aging of the world’s population leads to an increase in the prevalence of age-related diseases, including cognitive impairment. At the stage of dementia, therapeutic interventions become usually ineffective. Therefore, researchers and clinical practitioners today are looking for methods that allow for early diagnosis of cognitive impairment, including techniques that are based on the use of biological markers.
AIM: The aim of this literature review is to delve into scientific papers that are centered on modern laboratory tests for Alzheimer’s disease, including tests for biological markers at the early stages of cognitive impairment.
METHODS: The authors have carried out a descriptive review of scientific papers published from 2015 to 2023. Studies that are included in the PubMed and Web of Science electronic databases were analyzed. A descriptive analysis was used to summarized the gleaned information.
RESULTS: Blood and cerebrospinal fluid (CSF) biomarkers, as well as the advantages and disadvantages of their use, are reviewed. The most promising neurotrophic, neuroinflammatory, and genetic markers, including polygenic risk models, are also discussed.
CONCLUSION: The use of biomarkers in clinical practice will contribute to the early diagnosis of cognitive impairment associated with Alzheimer’s disease. Genetic screening tests can improve the detection threshold of preclinical abnormalities in the absence of obvious symptoms of cognitive decline. The active use of biomarkers in clinical practice, in combination with genetic screening for the early diagnosis of cognitive impairment in Alzheimer’s disease, can improve the timeliness and effectiveness of medical interventions.
53-62
INFORMATION
Celebrating a Storied History: Moscow Preobrazhenskaya Mental Hospital Marks its 245th Anniversary
Abstract
In 2022, Mental-health Clinic No. 4 named after P. B. Gannushkin, one of the oldest mental health institutions in Russia known as Preobrazhenskaya Hospital before the October Revolution of 1917, celebrated its 245th anniversary. The history of the hospital reflects all stages of the evolution of the basic principles and aspects of mental health care in Russia. On many occasions, the institution served as a platform for eminent researchers and clinicians to achieve scientific breakthroughs and their application in practice. This article is a review of the major milestones in the history of the hospital. It highlights the great achievements of its psychiatrists and presents some previously unpublished archival documents that offer a new perspective on the history of Preobrazhenskaya Hospital.
64-72