[WHEN MEDICATIONS ARE NOT ENOUGH - NEUROFEEDBACK AS A COMPLEMENTARY TREATMENT FOR POST-TRAUMATIC STRESS DISORDER - A CASE REPORT].

INTRODUCTION: Neurofeedback (NF) therapy is brain training using operant conditioning including real-time displays of brain activity to teach people how to regulate their brain function. We would like to present a treatment for a patient who experienced severe traumatic events on 7/10 including physical injury accompanied by difficulty sleeping for two months, nightmares, intrusive thoughts, difficulties in emotional regulation and difficulty in concentrating. Due to the complexity and difficulties in emotional regulation accompanied by severe sleep disturbances, it was decided to treat with medication in combination with neurofeedback. After several training sessions in addition to pharmaceutical treatment, significant relaxation was observed, there was an improvement in concentration and the patient was able to return to his work and normal social functioning. In addition, intrusive thoughts decreased in intensity and frequency.

[WHERE IS THE FRONTLINE? IT IS HERE].

INTRODUCTION: In the past few weeks, the staff of the Psychiatric Division at the Barzilai Medical Center have been personally, professionally, and socially involved with the impact of the "Swords of Iron " war. While the medical team has dealt with many intense security events in the past, it is clear that the magnitude of the significant impact with the high number of casualties in this war is unlike anything they have experienced before. Providing care to the wounded when there are no clear boundaries between the frontlines and the home front presents a significant challenge that the medical team is currently facing. The article reflects the impressions, experiences, challenges, and resilience of the medical team in the Psychiatry Department at the Barzilai Medical Center.

Association Between Behçet's Disease and Depression.

BACKGROUND: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression. OBJECTIVES: To evaluate the association between BD and depression, adjusting for established risk factors for depression. METHODS: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex. RESULTS: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37-2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39-2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18-39 years of age), low and high socioeconomical status, and non-smokers. CONCLUSIONS: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.

Are Chronic Pain Syndromes the Reason for Statin-associated Muscle Symptoms?

BACKGROUND: Statin-induced myalgia is defined as muscle pain without elevation of serum creatine phosphokinase levels and is a well-known complaint among statin users. Chronic pain syndromes affect a high percentage of the population. These pain syndromes may confound the reports of statin-induced myalgia. OBJECTIVES: To compare the occurrence of chronic pain among patients on statin therapy who developed myalgia with those who did not. METHODS: This study included 112 statin-treated patients, who were followed at the lipid center at Sheba Medical Center. Fifty-six patients had a diagnosis of statin-associated muscle symptoms (SAMS) and 56 did not. Verified questionnaires were used to assess the diagnoses of fibromyalgia, pain intensity, functional impairment, anxiety, and depression in the study population. RESULTS: Patients with statin myalgia were more likely to fulfil the diagnostic criteria for fibromyalgia than patients without statin myalgia (11 [19.6%] vs. 0, respectively). Patients in the SAMS group exhibited higher levels of anxiety and depression compared with the control group. Female sex, higher scores on the Brief Pain Inventory pain intensity scale, and a Hamilton rating scale level indicative of an anxiety disorder were found to be significant predictors for fibromyalgia in patients presenting with statin myalgia. CONCLUSIONS: A significant percentage of patients diagnosed with statin myalgia fulfilled the diagnostic criteria for fibromyalgia depression or anxiety disorder. Detection of these patients and treatment of their primary pain disorders or psychiatric illnesses has the potential to prevent unnecessary cessation of effective statin therapy.

The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis.

BACKGROUND: Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. MATERIALS AND METHODS: Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. RESULTS: Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01). CONCLUSIONS: This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.

Fibromyalgia and Its Consequent Disability.

BACKGROUND: Fibromyalgia is a common pain syndrome treated by physicians of many disciplines and presents with many co-morbidities. We reviewed the complexities in assessing disabilities in fibromyalgia patients and the complex interrelationships between patients, their working places, and the medical community regarding preserving productivity. Flexibility is essential to keep the patients functional and productive. Job loss is costly to both society and patients and joint measures are needed to prevent unemployment.

The Powers of Flowers: Evaluating the Impact of Floral Therapy on Pain and Psychiatric Symptoms in Fibromyalgia.

BACKGROUND: Fibromyalgia is a syndrome of unknown etiology that is characterized by widespread pain, which severely impairs quality of life. Several forms of occupational and alternative therapy have demonstrated beneficial effects in fibromyalgia patients. OBJECTIVES: To assess the effects of participation in a floral design course on physical and psychiatric symptoms in a cohort of fibromyalgia patients. METHODS: This study was conducted as an observational study. Women diagnosed with fibromyalgia over the age of 18 were recruited to participate in one of two 12-week flower design (floristry) courses. Demographic details, disease activity indices, and anxiety and depression scores were calculated for all participants at baseline, week 12, and study completion. Physical and mental health of the two groups were compared throughout the study time-points. RESULTS: The study was completed by 61 female fibromyalgia patients who were included in the final analyses; 31 patients participated in the first floristry course and 30 in the second. Significant improvements in the 36-Item Short Form Survey physical and mental health components, visual analog scale, Fibromyalgia Impact Questionnaire, Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale scores for the entire study population and for each group separately could be seen following participation in each floristry course. CONCLUSIONS: Participation in a floristry course may lead to a significant improvement in pain and psychiatric symptoms in fibromyalgia patients. These findings highlight the potential benefit of utilizing occupational therapy programs, such as a floristry course, for improving quality of life in fibromyalgia.

[ASSOCIATION OF OBESITY, SMOKING AND SOCIOECONOMIC STRATA WITH THE FIBROMYALGIA SYNDROME].

AIMS: This study aimed to examine a possible association between BMI levels, smoking and socio-economic status and the existence of fibromyalgia. BACKGROUND: Obesity is a worldwide epidemic with devastating impacts on the public's health. There are several indications that obesity might also be involved in the pathogenesis of chronic pain syndromes such as fibromyalgia. METHODS: Patients who were diagnosed with fibromyalgia were compared to population-based controls, matched in age and gender (by a ratio of 1:5). Body mass indices, smoking status and socioeconomic strata were retrieved from computerized medical records of the Clalit Health Services database. Body mass index was classified in WHO categories of underweight, normal, overweight and obese (<18.5, 18.5-<25, 25.0-<30, ≥30.0 kg/m2); χ2, t-tests, and logistic regression models were used to compare the study groups and assess the association between obesity and fibromyalgia. RESULTS: The study included 14,296 patients with fibromyalgia and 71,324 controls. Among patients with fibromyalgia the average BMI (body mass index) was higher than that of the controls 29.1± 6.2 vs. 28.0± 6.01, p<0.001) with every increment of 1 unit of the BMI score, there was an increment of 2.7% of the odds of having coexistent fibromyalgia. The chances of having fibromyalgia was 56% higher among subjects with obesity compared to individuals of normal weight. The data revealed that patients with fibromyalgia smoke more and belong to lower socioeconomic levels. CONCLUSIONS: Our findings demonstrate that obesity is significantly associated with a higher proportion of fibromyalgia. This finding underlines the role that obesity plays in inflammation and chronic pain.

High proportions of dementia among SLE patients: A big data analysis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting a wide range of systems including the peripheral and central nervous system. Cognitive impairment leading to dementia is one of the harmful central nervous system afflictions of SLE. The aim of this study was to investigate the association of SLE with dementia. METHODS: A cross-sectional study was conducted using Clalit Health Care database, the largest health maintenance organization in Israel with more than 4.4 million enrollees. Systemic lupus erythematosus patients were compared in a 1:5 ratio to age- and sex-matched controls. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. RESULTS: The study included 4886 SLE patients and 24 430 age-frequency- and sex-frequency-matched controls without SLE. The proportion of dementia was higher among SLE patients compared to controls (1.56% and 0.51%, respectively; P < .001). This finding was consistent across all age groups by univariate analysis. In a multivariate logistic regression analysis, SLE was significantly associated with dementia (odds ratio = 1.51, 95% confidence interval, 1.11-2.04). CONCLUSION: Systemic lupus erythematosus is significantly associated with dementia. This finding should give rise to search for SLE in patients with an ambiguous cause for dementia, especially those with an early onset cognitive decline.

Cross-sectional analysis of the associations between fibromyalgia and diabetes mellitus.

BACKGROUND: The fibromyalgia syndrome (FMS) is a chronic condition consisting of widespread musculoskeletal pain and tenderness together with mood and cognitive dysfunction. Diabetes mellitus (DM) is a common condition causing significant and detrimental morbidity and mortality. Data on the association between the two conditions is scarce and mainly based on small populations therefore lack solid evidence. OBJECTIVES: To evaluate the association of FMS with DM. MATERIAL AND METHODS: This cross-sectional study used the Clalit Health Services database, the largest Health Maintenance Organization in Israel, serving 4,400,000 members. FMS patients were compared to age- and sex-matched controls regarding chronic comorbid conditions. χ2 and student's t-tests were used for univariate analysis. RESULTS: The study included 14,296 FMS patients and 71,324 age- and sex-matched controls. The FMS group had a significantly higher proportion of DM patients compared to non-FMS controls (19.8% and 17.4 respectively; OR 1.17 , 95% CI: 1.12-1.23, p < 0.001). CONCLUSIONS: DM was found to be more common amongst FMS patients compared to matched controls to suggest that the pathophysiology of DM might lead a patient to develop FMS. Consequently, physicians treating DM patients should be aware of the possible risk and asses for clinical signs of FMS in order to diagnose and treat it in time to better their patients' quality of life and disease management.

Stroke among Rheumatoid Arthritis Patients: Does Age Matter? A Real-Life Study.

BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a chronic, debilitating autoimmune disease that affects the joints and it is known to be associated with cardiovascular morbidity. However, the association between RA and stroke among different age groups has not been explored. The objective of our study was to evaluate the association between RA and stroke in different age strata. METHODS: Cross-sectional study, utilizing the database of Israel's largest healthcare provider. The proportion of stroke was compared between patients diagnosed with RA and age- and gender-matched controls. The study sample was divided into 2 age groups: young (≤65 years) and elderly (>65 years). Multivariable analysis was performed using logistic regression. RESULTS: The study included 11,782 RA patients and 57,973 age- and gender-matched controls. RA patients, primarily young, had more cardiovascular risk factors than controls. Stroke rates were significantly elevated among young RA patients in comparison with controls (3.74 vs. 2.20%, respectively, p < 0.001). In multivariate analysis, RA was found to be independently associated with stroke (OR 1.18, 95% CI 1.09-1.28). CONCLUSION: RA is independently associated with stroke, especially among RA patients under 65 years, for whom cardiovascular risk factors were more prominent. Physicians should advise RA patients to manage their risk factors strictly.

[SERUM CYTOKINE CONCENTRATIONS ASSOCIATION WITH THE SEVERITY OF SYMPTOMS IN MAJOR DEPRESSION].

BACKGROUND: Mounting data are indicating that major depression is related to diverse functions of the immune system. Several observations indicate that cytokine concentrations might also relate to the intensity of depressive manifestations. In this study we assessed whether inflammatory and anti-inflammatory cytokine concentrations are associated with the intensity of the depressive features in a cohort of patients with major depression and in healthy normal controls. METHODS: A group of 25 patients with major depression all suffering from an acute deterioration of their mental status and all hospitalized in a psychiatric ward were assessed for the intensity of their depressive manifestations according to the Hamilton rating scale for depression and by the clinical global impression scale (CGI). In parallel, concentrations of serum IL-2R, IL-6, IL-8, IL-10 were analyzed by commercial ELISA kits. As comparators, a group of 25 healthy controls was analyzed. RESULTS: The levels of IL-6 were higher among patients with depression. A high degree of correlation was found between the scores measured by the Hamilton and CGI scales by which the intensity of depressive symptoms were ranked. Interestingly, within the group of patients with depression a negative correlation was detected between the IL-6 concentrations and the CGI scores while a positive correlation was found between the IL-10 concentration and IL-6 concentration. CONCLUSIONS: Our data indicate that the patients with depression differ from healthy individuals by their cytokine profile. Within this group of patients depressive features have a specific pattern and linkage to inflammatory and anti-inflammatory scores.

[NEUROPSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS].

INTRODUCTION: This review deals with the neuropsychiatric disorders resulting from systemic lupus erythematosus (SLE). SLE is a chronic autoimmune disease that impacts all systems in the human body, including the central nervous system. Neuropsychiatric symptoms in SLE are a common complication of the disease. This complication has significant implications for the severity of the illness. In most cases no thorough psychiatric assessment is performed during initial evaluation of the disease and no protocol or clear guidelines for treating the psychiatric symptoms in SLE are available. Early diagnosis of the psychiatric symptoms in SLE is critical since absence of treatment may result in severe psychiatric complications. Clinical pharmacological studies are needed in order to develop guidelines for treating psychiatric symptoms in SLE.

Family history of major depression and residual symptoms in responder and non-responder depressed patients.

BACKGROUND: Little is known about the extent to which a family history of major depression (MD) affects residual depressive symptoms in responder and non-responder patients suffering from MD. METHODS: Nine hundred eighty-six patients with MD were recruited within the context of a large multicenter project. Information about the family history of MD, as well as about total depressive symptoms and specific depressive clusters, was collected and analyzed. RESULTS: No significant difference was observed in overall depressive symptoms between patients with and those without a family history of MD. However, non-responder patients with a family history of MD showed significantly higher scores in core symptoms as compared with responder patients without a family history of MD. CONCLUSIONS: Non-responder MD patients with a positive family history of MD could represent a slightly different sub-group of MD patients with more consistent core depressive symptoms as compared with responder patients without a family history of MD. However, taking into account the retrospective assessment of data, the use of positive or negative family history as a dichotomous indicator of familial loading and the cross-sectional design of the present study, further research is needed to draw more definitive conclusions.

Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.

RATIONALE: Valproic acid (VPA) is commonly used as a second-line mood stabilizer or augmentative agent in severe mental illnesses. However, population pharmacokinetic studies specific to psychiatric populations are limited, and clinical predictors for the precision application of VPA remain undefined. OBJECTIVES: To identify steady-state serum VPA level predictors in pediatric/adolescent and adult psychiatric inpatients. METHODS: We analyzed data from 634 patients and 1,068 steady-state therapeutic drug monitoring (TDM) data points recorded from 2015 to 2021. Steady-state VPA levels were obtained after tapering during each hospitalization episode. Electronic patient records were screened for routine clinical parameters and co-medication. Generalized additive mixed models were employed to identify independent predictors. RESULTS: Most TDM episodes involved patients with psychotic disorders, including schizophrenia (29.2%) and schizoaffective disorder (17.3%). Polypharmacy was common, with the most frequent combinations being VPA + quetiapine and VPA + promethazine. Age was significantly associated with VPA levels, with pediatric/adolescent patients (< 18 years) demonstrating higher dose-adjusted serum levels of VPA (ß = 7.6±2.34, p < 0.001) after accounting for BMI. Women tended to have higher adjusted VPA serum levels than men (ß = 5.08±1.62, p < 0.001). The formulation of VPA (Immediate-release vs. extended-release) showed no association with VPA levels. Co-administration of diazepam exhibited a dose-dependent decrease in VPA levels (F = 15.7, p < 0.001), suggesting a potential pharmacokinetic interaction. CONCLUSIONS: This study highlights the utility of population-specific pharmacokinetic data for VPA in psychiatric populations. Age, gender, and co-administration of diazepam were identified as predictors of VPA levels. Further research is warranted to establish additional predictors and optimize the precision application of VPA in psychiatric patients.

Amygdala-derived-EEG-fMRI-pattern neurofeedback for the treatment of chronic post-traumatic stress disorder. A prospective, multicenter, multinational study evaluating clinical efficacy.

We conducted a prospective, single arm, multisite, multinational, open label trial assessing the safety and efficacy of a novel amygdala derived neurofeedback treatment, designated Amygdala-Derived-EFP, for chronic PTSD. Participants, including veterans and civilians, underwent screening, training, 15 neurofeedback sessions over 8 weeks and; baseline, termination (8 weeks) and 3 month post treatment assessments with validated measures. The primary endpoint was more than 50 % of the participants demonstrating a Minimally Clinically Important Difference (MCID) defined as a 6-point reduction, on the Clinician Administered PTSD Scale (CAPS-5) total score at 3 months. Secondary measures included the PCL-5, ERQ, PHQ-9, and CGI. Statistical analyses were performed using SAS®V9.4. The primary endpoint was met, with a CAPS-5 MCID response rate of 66.7 %. The average reduction in CAPS-5 total scores at 3 month follow up was 13.5 points, more than twice the MCID. Changes from baseline in CAPS-5, PCL-5, PHQ-9 scores at 8 weeks and the 3 month follow-up demonstrated statistically significant improvements in response and; demonstrated effect sizes ranging from 0.46 to 1.07. Adverse events were mild and resolved after treatment. This study builds on prior research demonstrating similar outcomes using amygdala-derived neurofeedback. Positive attributes of this therapy include monitoring by non-physician personnel, affordability, accessibility, and tolerability.

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

The impact of adverse life events on clinical features and interaction with gene variants in mood disorder patients.

BACKGROUND: Adverse life events are precipitating and maintenance factors for mood and anxiety disorders. However, the impact of such events on clinical features and treatment response is still unclear. SAMPLING AND METHODS: The aim of this study was to investigate whether specific adverse events (early parental loss and physical abuse) influence clinical features in a sample of 1,336 mood disorder patients, and whether genetic parameters interact with adverse events to influence treatment outcomes in a subsample of 252 subjects. Participants were collected in the context of a European multicenter study and treated with antidepressants at adequate doses for at least 4 weeks. We focused on two genes (BDNF and CREB1) due to prior evidence of association with treatment outcomes in the same sample. RESULTS: Patients with a history of physical abuse had higher suicidal risk (including history of attempts), comorbid panic disorder, posttraumatic stress disorder and alcohol dependence compared to non-abused patients. Experience of early parental loss was a less detrimental type of life stressor. Treatment response was not affected by adverse events. No gene-environment interaction was found with genetic variations, using a corrected significance level. CONCLUSIONS: A limitation of the present study is that the subsample is too small for detecting gene-environment interactions. The clinical message of our findings is that mood disorder patients with a history of physical abuse showed a worse clinical profile, characterized by higher comorbid Axis I psychopathology and increased suicidal behavior.

[Guidelines for the diagnosis and treatment of the fibromyalgia syndrome].

Over the past years, considerable progress has been made in understanding the pathogenesis of the fibromyatgia syndrome and the evidence based approach to the diagnosis and management has been significantty extended. The purpose of the current project is to develop practicat and evidence based guidetine recommendations for the Israeli health care system. A panet of physicians with clinical and research experience in the fibromyalgia field was convened under the auspices of the Israeli Rheumatology Association. A systematic review was performed on the current literature regarding the diagnosis and treatment of fibromyalgia. Using an interactive discussion procedure, recommendations were reached and expert opinion was introduced where evidence was considered incomplete. The panel recommendations underline the importance of concomitant and integrated medical therapy, such as serotonin and noradrenaline reuptake inhibitor (SNRI) anti-depressants or gamma-aminobutyric acid (GABA) related anti-epileptics, with regular aerobic physical exercise.

The possible onset of fibromyalgia following acute COVID-19 infection.

INTRODUCTION: The exact pathogenesis of fibromyalgia (FM) syndrome is unclear. However, various infectious have been implicated with the development of FM after their acute phase. We aimed to investigate the incidence of FM syndrome among convalesced individuals following hospitalization for Acute Coronavirus Disease-2019 (COVID-19). METHODS: We performed a cross-sectional study on patients who were discharged after COVID-19 hospitalization from the Sheba Medical Center, Israel, between July 2020 to November 2020. A phone interview was performed consisting of the following questionnaires: the Fibromyalgia Survey Diagnostic Criteria Questionnaire, Sense of Coherence Questionnaire to evaluate resilience, and the Subjective Traumatic Outlook Questionnaire to assess the associated psychological aspects of the trauma. The incidence of post-COVID FM was calculated and regression models were performed to identify predictors. RESULTS: The study population consisted of 198 eligible patients who completed the phone interview. The median age was 64 (52-72) and 37% were women. The median follow-up was 5.2 months (IQR 4.4-5.8). The incidence of FM was 15% (30 patients) and 87% (172 patients) had at least one FM-related symptom. Female gender was significantly associated with post-COVID FM (OR 3.65, p = 0.002). In addition, high median Subjective Traumatic Outlook scores and low median Sense of Coherence scores were both significantly associated with post-COVID FM (OR 1.19, p<0.001 and OR 0.92, p<0.001, respectively). CONCLUSIONS: FM is highly prevalent among COVID-19 convalescent patients. Our finding suggests that a significant subjective traumatic experience and a low resilience are highly associated with post-COVID FM.