The association between systemic lupus erythematosus and bipolar disorder - a big data analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that has a wide variety of physical manifestations, including neuropsychiatric features. Bipolar disorder (BD) is a chronic, episodic illness, that may present as depression or as mania. The objective of this study was to investigate the association between SLE and BD using big data analysis methods. METHODS: Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of BD in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis, adjusting for confounders. The study was performed utilizing the chronic disease registry of Clalit Health Services medical database. RESULTS: The study included 5018 SLE patients and 25,090 matched controls. BD was found in a higher prevalence among SLE patients compared to controls (0.62% vs. 0.26%, respectively, P<0.001). BD patients had a greater prevalence of smokers compared to non-BD patients (62.5% vs 23.5%, respectively, P<0.001). In a multivariate analysis, smoking and SLE were both found to be significantly associated with BD. CONCLUSIONS: SLE was found to be independently associated with BD. These findings may imply that an autoimmune process affecting the central nervous system among SLE patients facilitates the expression of concomitant BD.

Schizophrenia among patients with systemic lupus erythematosus: population-based cross-sectional study.

AIMS: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease involving multiple organs, including the central nervous system. Evidence of immune dysfunction exists also in schizophrenia, a psychiatric illness involving chronic or recurrent psychosis. The aim of our study was to investigate if there is an epidemiological association between SLE and schizophrenia. METHOD: A cross-sectional study was conducted comparing patients with SLE with age and gender-matched controls regarding the proportion of patients with comorbid schizophrenia. χ 2- and t-tests were used for univariate analysis, and interaction of schizophrenia with SLE across strata of covariates was checked. A logistic regression model was used for multivariate analysis. The study was performed utilising the medical database of Clalit Health Services in Israel. RESULTS: The study included 5018 patients with SLE and 25 090 controls. SLE patients had a female predominance, and a higher proportion of smoking compared with age and sex-matched controls. In multivariate analysis, SLE was found to be independently associated with schizophrenia while controlling for age, gender, socioeconomic status (SES) and smoking (OR 1.33, p = 0.042). CONCLUSIONS: We found a positive association between SLE and schizophrenia across patients of different age, gender and SES. This association can contribute to understanding the pathophysiology of the two disorders and may also have clinical implications for earlier as well as better diagnosis and treatment.

A randomised, double-blinded study comparing giving etoricoxib vs. placebo to female patients with fibromyalgia.

OBJECTIVES: Current therapeutic approaches to fibromyalgia syndrome (FMS) do not provide satisfactory pain control to a high percentage of patients. This unmet need constantly fuels the pursuit for new modalities for pain relief. This randomised, double-blind, controlled study assessed the efficacy and safety of adding etoricoxib vs. placebo to the current therapeutic regimen of female patients with FMS. METHODS: In this double-blind, placebo-controlled study, female patients were randomised to receive either 90 mg etoricoxib once daily or placebo for 6 weeks. Several physical and mental parameters were assessed throughout the study. The primary end-point was the response to treatment, defined as ≥ 30% reduction in the average Brief Pain Inventory score. Secondary outcomes were changes in the Fibromyalgia Impact Questionnaire, SF-36 Quality of Life assessment questionnaire and Hamilton rating scales for anxiety and depression. RESULTS: Overall, 73 patients were recruited. Although many outcome measures improved throughout the study, no difference was recorded between the etoricoxib- and placebo-treated groups. The Brief Pain Inventory, Fibromyalgia Impact Questionnaire, The Hamilton Anxiety and Depression scores did not differ between the two groups. CONCLUSIONS: This is the first randomised, double-blind study assessing the effect of adding etoricoxib to pre-existing medications for female patients with FMS. Although being mildly underpowered this study clearly has shown that etoricoxib did not improve pain scores and did not lead to any beneficial mental or physical effects.

Physical co-morbidity among treatment resistant vs. treatment responsive patients with major depressive disorder.

Co-morbid physical illness has been suggested to play an important role among the factors contributing to treatment resistance in patients with major depressive disorder. In the current study we compared the rate of physical co-morbidity, defined by ICD-10, among a large multicenter sample of 702 patients with major depressive disorder. A total of 356 of the participants were defined as treatment resistant depression (TRD) patients-having failed two or more adequate antidepressant trials. No significant difference was found between TRD and non-TRD participants in the prevalence of any ICD-10 category. This finding suggests that although physical conditions such as diabetes, thyroid dysfunction, hypertension, ischemic heart disease, and peptic diseases are often accompanied by co-morbid MDD, they do not necessarily have an impact on the course of MDD or the likelihood to respond to treatment. Marginally higher rates of co-morbid breast cancer, migraine and glaucoma were found among TRD participants. Possible explanations for these findings and their possible relation to TRD are discussed.

The economic impact of depression: resistance or severity?

Treatment-Resistant Depression (TRD) affects 60 to 70% of patients with Major Depressive Disorder (MDD). The economic impact of depression in general, and of TRD specifically, was found to be relatively high. As the course of depression can be defined both by the severity of the disease and by the resistance to treatment, the question of the unique contribution of MDD severity vs. resistance to the economic burden of depression is being raised. One hundred and seven unipolar MDD patients, all treated for at least 4weeks, were enrolled in the study. Patients were assessed for their current MDD severity using the Hamilton Depression Rating Scale (HDRS) and past treatments, and for medical-related costs (number of blood and imaging tests, visits paid to physicians, psychiatric hospitalizations) and incapacity-related costs (number of working days lost) during the last episode. TRD and non-TRD patients were, respectively, 39.3% and 60.7% of the patients recruited for the study. TRD patients had more severe depression, and higher costs for imaging tests, physician visits, psychiatric hospitalizations, and number of working days lost. In addition, higher MDD severity was found to be associated with higher costs. Finally, when controlling for the shared variance of TRD and MDD severity, by using residual scores, TRD was associated with higher costs, but MDD severity was no longer related to costs. While both resistance and severity are associated with higher direct and indirect costs, our findings suggest that TRD may be the main factor in determining the economic burden of depression.

Serious life events among resistant and non-resistant MDD patients.

BACKGROUND: Over 60% of patients with major depressive disorder (MDD) do not respond fully to therapy. Half of them eventually will not respond at all and will be referred to as treatment resistant depression (TRD) patients. Stressful life events were found to be associated with MDD and were also found to affect the course of the disease. We hypothesize that negative life events might be an independent risk factor for TRD. METHODS: One hundred and seven unipolar MDD patients, all treated for at least 4 weeks, were enrolled in the study. Patients were assessed on their psychiatric and medical history, and seven categories of stressful life events. RESULTS: 39.3% of participants were defined as TRD patients and 60.7% as non-TRD. TRD patients had more severe depression, more past suicide attempts, more hospitalizations, longer episodes, and received more benzodiazepines, antipsychotics, and ECT. Job loss and financial stress were more prevalent among the TRD group. Overall, the TRD patients had more negative life events than responders. LIMITATIONS: This is a retrospective study. In addition, the definition of TRD was done dichotomically, therefore the association between number of stressful life events and the degree of resistance was not tested. CONCLUSIONS: Job loss and financial distress were found to predict TRD. The loss of a parent and severe health conditions were not associated with TRD, suggesting that events affecting the development of MDD, do not necessarily affect the treatment outcome.

Physical activity protects male patients with post-traumatic stress disorder from developing severe fibromyalgia.

OBJECTIVES: Fibromyalgia syndrome (FMS) has been associated with various psychiatric and other, ill-defined disorders. We recently showed that fibromyalgia is more prevalent in men suffering from combat-related Post Traumatic Stress Disorder (PTSD). In this paper we analyze the relationship between engagement in physical activity, the psycho-metric traits of PTSD and the future development of FMS. METHODS: Fifty-five male patients, all known to have combat-related PTSD, were investigated for the presence of fibro-myalgia according to the American College of Rheumatology (ACR) criteria. Each patient completed questionnaires characterizing his quality of sleep, and the Sheehan Disability Scale measuring performance in the familial, social and vocational spheres. Additionally, each of the enrollees was interviewed by an experienced psychiatrist, who then completed a Clinician Administered PTSD Scale, a Clinical Global Impression Scale, and calculated an SF-36 score. Each patient was asked whether he exercised often, occasionally or not at all. The data was analyzed by the chi2 test and by ANOVA. RESULTS: PTSD patients who also suffered from FMS had a more severe form of disease as measured by the Clinician Administered PTSD Scale (CAPS) score, 88.2 +/- 14.0 (n = 28) compared to 97.6 +/- 13.2 of patients with PTSD and FMS (n = 27) (p = 0.013, F(d.f 2)-6.61, ANOVA test). Interestingly, engaging in physical exercise was also associated with less severe disease. When the patients were analyzed based on their tender point count (0-5, 6-10, or > 11), the number of tender points decreased with increasing physical activity (p = 0.02, chi2(d.f.-4) = 11.3). CONCLUSION: Physical exercise in male patients with combat-related PTSD provides protection from the future development of fibromyalgia. Furthermore, physical activity is related in this group of patients to a better perception of their quality of life.

Obsessive compulsive disorder: serotonin and beyond.

OCD was considered a rare, treatment refractory disorder of psychological origin, up until 20 years ago. Research in the last two decades has altered the perspectives regarding OCD. It is now clear that OCD is a prevalent disorder--about 2% of the population suffer from OCD--and that it is amenable both to psychological (cognitive-behavioural approach) and pharmacological intervention (with serotonergic medication). The biochemical and neuroanatomical (the frontal basal-thalamo cortical circuit) pathophysiology of OCD is also beginning to emerge. OCD is unique with regards to its specific response to serotonergic medication that blocks reuptake. Clomiprimine, fluoxetine, fluvoxemine, paroxetine, sertraline and citalopram were all found to be effective treatments for OCD based on large, multicentre, double-blind, placebo-controlled studies. As only serotonergic medications appear to be effective in OCD, the serotonergic hypothesis has been formulated and tested. Indeed, pharmacological challenges with specific serotonin agonists such as mCPP and sumatriptan, which were associated with transient exacerbation of OCD symptoms, are in line with the specific role of 5HT in the pathogenesis of OCD. However, this serotonergic hypothesis, while necessary, is not sufficient. It is clear that the dopaminergic and autoimmune mechanism are also implicated in the pathogenesis of OCD. Further studies are required to understand the relevance of the serotonergic and non-serotonergic systems in OCD, and to highlight the various possible subtypes of this intriguing disorder.

Update on the epidemiology, diagnosis, and treatment of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a maladaptive, pathological response to a traumatic event which is currently underdiagnosed and undertreated. This results in part from a lack of awareness regarding the prevalence of the disorder. It has been estimated that at least one third of the general population will be exposed to severe trauma throughout their lifetime, out of which approximately 10 % to 20 % develop PTSD. A prevalence of 3 % to 6 % of PTSD in the general population, found in several studies, corresponds well with these figures. Both the type of trauma and the personal characteristics of the individual involved are associated with the probability of developing PTSD. The Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) gives four diagnostic criteria: (i) exposure and emotional response to a traumatic event; (ii) reexperiencing; (iii) avoidance; and (iv) increased physiological arousal, along with severe impairment in occupational, social, and interpersonal functioning. The rate of comorbidity with other mental disorders is high, particularly for major depression, anxiety disorders, and substance abuse. Different types of psychological intervention, including cognitive-behavioral therapy and a host of pharmacological interventions, have been tried. Selective serotonin reuptake inhibitors (SSRIs) are currently the most widely researched agents with consistent, though modest, therapeutic effects. Other compounds, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have also been found to be effective, although their use is limited due to side effects. PTSD is a psychobiological phenomenon in response to psychological trauma, which represents maladaptive neurobiological deregulation and psychological dysfunction, and awaits further recognition and research.