Immunological Indicators of Infl ammation in Late-Life Bipolar Disorder

The aim of the study was to determine the immune markers of infl ammation in the blood plasma of the elderly patients with bipolar affective disorders (BD) in relation to the clinical specifi cities of the disease. Patients and methods: 134 blood samples from the elderly patients aged from 52 to 88 years old (mean age 66.7 ± 7.7 years) with diagnose of bipolar disorder were examined. Infl ammatory markers in the blood plasma were determined as follows: the enzymatic activity of leukocyte elastase (LE) and the functional activity of the D1-proteinase inhibitor (D1-PI), as well as the level of autoantibodies (aAB) to S100b and myelin basic protein (MBP), and the protease inhibitor index (PII), which was the ratio of LE and D1-PI activity and characterized the activity of the proteolytic system as the most important component of infl ammation. Cluster analysis was used to reveal immunotypes. Results and discussion: а signifi cant increase in D1-PI and the level of aAB to S100b was revealed in elderly patients diagnosed with bipolar disorders, as well as low proteolytic activity of infl ammation (according to PII). Immune markers of infl ammation in different types of affective episodes (depressions, manias, mixed affective states) and in therapeutic remission did not differ from each other. Immunological parameters in elderly patients with bipolar disorders depended on the severity degree of the affective disorder. A relationship was found between the severity of depression and the level of aAB to S100b; the difference between mania and hypomania in terms of LE and PII activity was shown; in mixed affective states immunological parameters differed from the control only in moderate disorders. Remission with residual symptoms differed from asymptomatic therapeutic remission in terms of LE and PII activity. The two identifi ed clusters (immunotypes) differed in the activity of LE and PII. Conclusion: the results indicated the participation of infl ammation in the pathogenesis of bipolar disorder, and the isolated immunotypes confi rmed the clinical diversity of the disease. The study of the pathogenetic signifi cance of infl ammation and the identifi cation of various immunotypes was aimed at search for new therapy targets, taking into account the contribution of infl ammation.

HLA-DRB1 and HLA-DQB1 genetic diversity modulates response to lithium in bipolar affective disorders

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLiGen) has recently identified genetic markers associated with treatment responses to Li in the human leukocyte antigens (HLA) region. To better understand the molecular mechanisms underlying this association, we have genetically imputed the classical alleles of the HLA region in the European patients of the ConLiGen cohort. We found our best signal for amino-acid variants belonging to the HLA-DRB1*11:01 classical allele, associated with a better response to Li (p < 1 × 10−3; FDR < 0.09 in the recessive model). Alanine or Leucine at position 74 of the HLA-DRB1 heavy chain was associated with a good response while Arginine or Glutamic acid with a poor response. As these variants have been implicated in common inflammatory/autoimmune processes, our findings strongly suggest that HLA-mediated low inflammatory background may contribute to the efficient response to Li in BD patients, while an inflammatory status overriding Li anti-inflammatory properties would favor a weak response.

Comorbidity Patterns of Mood Disorders in Adult Inpatients: Applying Association Rule Mining

This study explored physical and psychiatric comorbidities of mood disorders using association rule mining. There were 7709 subjects who were patients (19 years old) diagnosed with mood disorders and included in the data collected by the Korean National Hospital Discharge In-depth Injury Survey (KNHDS) between 2006 and 2018. Physical comorbidities (46.17%) were higher than that of psychiatric comorbidities (27.28%). The frequent comorbidities of mood disorders (F30–F39) were hypertensive diseases (I10–I15), neurotic, stress-related and somatoform disorders (F40–F48), diabetes mellitus (E10–E14), and diseases of esophagus, stomach, and duodenum (K20–K31). The bidirectional association path of mood disorders (F30–F39) with hypertensive diseases (I10–I15) and diabetes mellitus (E10–E14) were the strongest. Depressive episodes (F32) and recurrent depressive disorders (F33) revealed strong bidirectional association paths with other degenerative diseases of the nervous system (G30-G32) and organic, including symptomatic and mental disorders (F00–F09). Bipolar affective disorders (F31) revealed strong bidirectional association paths with diabetes mellitus (E10–E14) and hypertensive diseases (I10–I15). It was found that different physical and psychiatric disorders are comorbid according to the sub-classification of mood disorders. Understanding the comorbidity patterns of major comorbidities for each mood disorder can assist mental health providers in treating and managing patients with mood disorders.

Neurophysiological Subtypes of Depressive Disorders

Background: the clinical polymorphism of depressive disorders, together with the available data on the different responses of patients to treatment, motivate modern neuroscience to search for models that can explain such heterogeneity.Objective: to identify neurophysiological subtypes of depressive disorders.Patients and methods: 189 patients with moderate depression in the structure of a depressive episode (n = 42), recurrent depressive (n = 102) and bipolar affective disorders (n = 45); 56 healthy subjects. Clinical-psychopathological, psychometric, neurophysiological and statistical research methods were used in the work.The results: with the help of coherent EEG analysis, it is possible to identify at least 6 subtypes of the disorder, which characterize various branches of the pathogenesis of affective pathology, which go beyond the currently accepted nomenclature. The selected subtypes were determined by the profi les of dysfunctional interaction of various cortical zones in the alpha, beta and gamma ranges of the EEG. Subtype 1 was characterized by a decrease relative to the norm of imaginary alpha-coherence between the right parietal and left central, right parietal and left anterior temporal, as well as the right parietal and right anterior temporal EEG leads (P4-C3, P4-F7, P4-F8) and explained part of depressions, in the pathogenesis of which the leading role was played by violations of the promotion of positive and suppression of negative affect. Subtype 2 — an increase in beta-2-imaginary-coherence between the frontal leads of the left and right hemispheres, between the left frontal and right central cortex (F3-F4; F3-C4) and its decrease between the central cortical zones (C4-C3), in clinical terms this subtype was characterized by a persistent hedonic response and was associated with the clinical picture of atypical depression. Subtype 3 — an increase in imaginary alpha-coherence between the frontal (F4-F3) and its decrease between the central leads of the left and right hemisphere (C4-C3), correlated with the severity of depressive rumination. Subtype 4 — a decrease in imaginary alpha-coherence between the anterior temporal and frontal, as well as the anterior temporal and central cortex of the right hemisphere (F8-F4 and F8-C4), explained part of the depressions that developed against the background of avoidance personality disorder. Subtype 5 — a decrease in imaginary gamma coherence between the frontal and parietal, as well as the central and occipital cortical zones of the left hemisphere (F3-P3 and C3-O1), was associated with an outwardly oriented utilitarian style of thinking (alexithymia). Subtype 6 — a decrease in imaginary beta-1 coherence between the left central and right anterior temporal cortex (C3-F8), explained part of the depression with phobic and hypochondriacal disorders in the structure of recurrent depressive disorder. Such a clinical and biological typology seems new and promising in terms of searching for specifi c neurophysiological disorders in different types of depression and, accordingly, reaching differentiated therapeutic recommendations.

Rationale and Design of Assessing the Effectiveness of Short-Term Low-Dose Lithium Therapy in Averting Cardiac Surgery-Associated Acute Kidney Injury: A Randomized, Double Blinded, Placebo Controlled Pilot Trial

Background: Burgeoning pre-clinical evidence suggests that therapeutic targeting of glycogen synthase kinase 3β (GSK3β), a convergence point of multiple cellular protective signaling pathways, confers a beneficial effect on acute kidney injury (AKI) in experimental models. However, it remains unknown if GSK3β inhibition likewise mitigates AKI in humans. Cardiac surgery associated acute kidney injury (CSA-AKI) poses a significant challenge for clinicians and currently the only treatment available is general supportive measures. Lithium, an FDA approved mood stabilizer, is the best-known GSK3β inhibitor and has been safely used for over half a century as the first line regimen to treat bipolar affective disorders. This study attempts to examine the effectiveness of short term low dose lithium on CSA-AKI in human patients.Methods/Design: This is a single center, prospective, randomized, double blinded, placebo controlled pilot study on patients undergoing cardiac surgery with cardiopulmonary bypass. Patients will be randomized to receive a small dose of lithium or placebo treatment for three consecutive days. Renal function will be measured via creatinine as well as novel AKI biomarkers. The primary outcome is incidence of AKI according to Acute Kidney Injury Network (AKIN) criteria, and secondary outcomes include receipt of new dialysis, days on dialysis, days on mechanical ventilation, infections within 1 month of surgery, and death within 90 days of surgery.Discussion: As a standard selective inhibitor of GSK3β, lithium has been shown to exert a beneficial effect on tissue repair and regeneration upon acute injury in multiple organ systems, including the central nervous system and hematopoietic system. In experimental AKI, lithium at small doses is able to ameliorate AKI and promote kidney repair. Successful completion of this study will help to assess the effectiveness of lithium in CSA-AKI and could potentially pave the way for large-scale randomized trials to thoroughly evaluate the efficacy of this novel regimen for preventing AKI after cardiac surgery.Trial Registration: This study was registered prospectively on the 17th February 2017 at ClinicalTrials.gov (NCT03056248, https://clinicaltrials.gov/ct2/show/NCT03056248?term=NCT03056248&amp;draw=2&amp;rank=1).

Effectiveness of Psycho-Education Program for Knowledge of Family Caregivers of Patient’s with BAD at El-tigani El-mahi Psychiatric Teaching Hospital, Sudan, 2017- 2019

Background: Psycho education is among the most effective of the evidence-based practices that have emerged in both clinical trials and community settings, it showed weighed excellent benefits when administered to those with bipolar affective disorders, reducing both re-hospitalization rates and decreasing the number of days a person spends in the hospital .Aim: The study aim at assessing the effectiveness of psycho-education for family caregivers of patients with bipolar affective disorders at El-Tegani El-Mahi psychiatric teaching Hospital, Sudan, October 2017 to March 2018.Methods: This study is a quasi-experimental pre/post-tests hospital based, the sample consisted of (73) family caregivers who were all available at the hospital during the period of the data collection. They selected by total cover of all family caregivers close with patients. Data was collected by the use of Structured questionnaire to assess the family caregiver knowledge by likert scale, data was analyzed by Statistical Package for Social Science (SPSS) version 20.and presented figure and tables. Results: the study revealed that the mean score of knowledge before the psycho-education: 28.9. Their knowledge is poor according to compared with the overall mean knowledge post psycho-education were 73.0 with (p.value=,000).Conclusion & recommendation: Psycho education highly significance and improved the knowledge among the family caregivers of the patients with Bipolar Affective Disorders, the recommended establishment of collaborative relationship with families and educational interventions by the nurse under the guidance of the Psychiatric Hospital.

Affective and Psychotic Disorders in War-Torn Eastern Part of the Democratic Republic of the Congo: A Cross-Sectional Study

Background. There is lack of information about prevalence of affective and psychotic disorders triggered by traumatic events among people living in war-affected regions. This study is aimed at determining the prevalence rate of affective and psychotic disorders and the associated factors in a war-torn eastern part of Democratic Republic of the Congo. Methods. This epidemiological cross-sectional descriptive study was carried out from 1st January 2019 to 31st December 2019 at Cepima and Muyisa health centers. This study enrolled 344 patients that had experienced traumatic events in Eastern Democratic Republic of the Congo from the 1119 participants, of whom 229 had positive bipolar affective disorder and 115 patients had psychotic disorders. Results. The results revealed that bipolar affective disorders were two times more than psychotic disorders. Sexual abuse, sudden death of a relative, kidnapping, the physical torture, and childhood trauma were the psychological factors correlated to the occurrence of bipolar affective and psychotic disorders. Conclusions. It was concluded that the traumatic experiences were precursors for the occurrence of bipolar affective and psychotic spectrum disorders.

Exploring the role of therapeutic drug monitoring and regular supervision in optimizing quality of life in patients of bipolar affective disorder receiving lithium therapy in a tertiary care teaching hospital: a prospective observational study

Background: Lithium is considered first line drug effective in treating manic and mixed episodes of bipolar affective disorders throughout the globe. But the chronic and heterogenous nature of disease, along with toxicity of lithium often make patients non-adherent to medication as well as diminished health related quality of life. Present study was done to find out the prospect of regular supervision and follow up with therapeutic drug monitoring in optimization of lithium therapy based on health-related quality of life outcomes.Methods: It was a prospective, non-randomized, observational study of a cohort of subjects who are suffering from bipolar affective disorders and on lithium therapy. Patients were regularly followed up with therapeutic drug monitoring and personalized interview with questionnaires like WHO Quality of Life Score (QOL-Bref), Montgomery-Asberg Depression Scale (MADRS) and Medication Adherence Rating Scale (MARS).Results: Results revealed there was significant improvement in health-related quality of life of patients who were monitored with therapeutic drug monitoring and prescribed lithium therapy.Conclusions: Hence to maintain patients’ quality of life improved throughout the cycle of bipolar disorder spectrum, regular follow-up visits with monitoring of serum levels of lithium is needed, so that adverse effects would be minimal and adherence to medication become optimal. These optimal dosing resulting in optimal benefit to patients can be achieved with the involvement of clinical pharmacological consultation.

Revisiting the role of therapeutic drug monitoring in optimizing treatment outcomes in patients of bipolar affective disorders receiving lithium therapy: a prospective observational study

Background: Lithium continues to be considered first-line therapy for treatment of acute mania, acute mixed bipolar disease and long-term prophylaxis of bipolar disorder. Present study was done to study the pattern of drug therapy in bipolar affective disorder patients with special reference to lithium in the routine psychiatric outpatients care setting of a tertiary care teaching hospital as well as to understand the prospect of therapeutic drug monitoring in optimization of lithium therapy based on outcome.Methods: It was a prospective, non-randomized, observational study of a cohort of subjects who are suffering from bipolar affective disorders and on lithium therapy. Patients were prospectively followed up three monthly for three visits with therapeutic drug monitoring of their plasma lithium level, as and when advised by the treating physician, and pre-formed questionnaires.Results: Results revealed there was significant improvement in symptoms of patients who were monitored with therapeutic drug monitoring and prescribed lithium therapy in accordance with clinical pharmacological consultation for optimal dosing resulting in optimal benefit to patients.Conclusions: With regular therapeutic monitoring, optimal target serum lithium levels can be achieved with dosage modifications thereby reducing the risk of toxicity with improved drug compliance. Thus, individualization of dosing and optimization of treatment can be achieved by dependable analytical laboratory services, better psycho-education, family support and overall a disease-based management team approach with the involvement of clinical Pharmacologist to meet the complexities of lithium therapy.