Daniela Amital

Double-blind placebo-controlled pilot study of sertraline in military veterans with posttraumatic stress disorder.

The efficacy of sertraline in the treatment of civilian posttraumatic stress disorder (PTSD) has been established by two large placebo-controlled trials. The purpose of the current pilot study was to obtain preliminary evidence of the efficacy of sertraline in military veterans suffering from PTSD. Outpatient Israeli military veterans with a DSM-III-R diagnosis of PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50–200 mg/day; N = 23, 83% male, mean age = 41 years) or placebo (N = 19, 95% male, mean age = 38 years). Efficacy was evaluated by the Clinician-Administered PTSD Scale (CAPS-2) and by Clinical Global Impression Scale-Severity (CGI-S) and -Improvement (CGI-I) ratings. Consensus responder criteria consisted of a 30% or greater reduction in the CAPS-2 total severity score and a CGI-I rating of “much” or “very much” improved. The baseline CAPS-2 total severity score was 94.3 ± 12.9 for sertraline patients, which is notably higher than that reported for most studies of civilian PTSD. On an intent-to-treat endpoint analysis, sertraline showed a numeric but not statistically significant advantage compared with placebo on the CAPS-2 total severity and symptom cluster scores. In the study completer analysis, the mean CGI-I score was 2.4 ± 0.3 for sertraline and 3.4 ± 0.3 for placebo (t = 2.55, df = 30, p = 0.016), CGI-I responder rates were 53% for sertraline and 20% for placebo (χ2 = 3.62, df = 1, p = 0.057), and combined CGI-I and CAPS-2 responder rates (≥30% reduction in baseline CAPS-2 score) were 41% for sertraline and 20% for placebo (χ2 = 1.39, df = 1, p = 0.238). Sertraline treatment was well tolerated, with a 13% discontinuation rate as a result of adverse events. This pilot study suggests that sertraline may be an effective treatment in patients with predominantly combat-induced PTSD, although the effect size seems to be somewhat smaller than what has been reported in civilian PTSD studies. Adequately powered studies are needed to confirm these results and to assess whether continued treatment maintains or further improves response.

Stroop performance in major depression: Selective attention impairment or psychomotor slowness?

BACKGROUND Numerous neuropsychological studies reported impaired Stroop performance in major depressive disorder (MDD) patients. METHODS The present study attempted to identify possible neuropsychological mechanisms involved in this impairment in untreated MDD outpatients (n=75) as compared to healthy subjects (n=83). Inspection Time, Finger Tapping, Simple and Choice Reaction Time were considered as measures of perceptual, motor, psychomotor speed, and response selection, respectively. RESULTS MDD patients performed significantly slower than healthy controls in the neutral and the congruent conditions, but not in the incongruent ones. In order to identify predictors of Stroop performance, linear hierarchical regressions analyses were performed. Age, motor and psychomotor speed were predictors of response time and accuracy on Stroop performance. Significant correlations between response time and the number of errors in all three Stroop conditions were found in MDD patients, while such a correlation was obtained in the healthy controls only in the incongruent condition. LIMITATIONS Although education was included as a covariate in our analyses, suggesting that the observed effects could not be ascribed to education differences, further testing with education-matched samples is warranted. CONCLUSIONS Our study shows that the Stroop task performance is affected by both aging and MDD. Impairment in the Stroop performance can be predicted by psychomotor slowness and by vigilance level in MDD outpatients, but not by impairment of selective attention per se.

Bipolar disorder associated with rheumatoid arthritis: A case-control study.

BACKGROUND Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with systemic comorbidities. Recent data suggests that patients with RA have increased prevalence of the bipolar disorder. The current study investigates the association between RA and bipolar disorder. METHODS A case-control study was conducted as Patients with RA were compared with age- and gender-matched controls regarding the prevalence of bipolar disorder. Pearson χ(2) test was used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services. RESULTS The study included 11,782 patients with RA and 57,973 age- and gender-matched controls. The prevalence of Bipolar disorder in patients with RA was increased compared with the prevalence in controls (0.6% and 0.4% respectively, p=0.036). However, in a multivariate analysis the association between RA and Bipolar disorder was not significant, whereas smoking is positively correlated with Bipolar disorder (p<0.001). CONCLUSIONS By univariate analysis our data implied that patients with RA have a greater prevalence of bipolar disorder than matched controls. However, our analysis suggests that this association may have been confounded by smoking status. Further research is warranted before making inferences about this association in the level of clinical practice.

Evaluation of the role of MAPK1 and CREB1 polymorphisms on treatment resistance, response and remission in mood disorder patients

Treatment resistant depression (TRD) is a significant clinical and public health problem. Among others, neuroplasticity and inflammatory pathways seem to play a crucial role in the pathomechanisms of antidepressant efficacy. The primary aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within two genes implicated in neuroplasticity and inflammatory processes (the mitogen activated protein kinase 1, MAPK1 (rs3810608, rs6928, rs13515 and rs8136867), and the cyclic AMP responsive element binding protein 1, CREB1 (rs889895, rs6740584, rs2551922 and rs2254137)) was associated with antidepressant treatment resistance (according to two different definitions), in 285 Major Depressive Disorder (MDD) patients. As secondary aims, we investigated the genetic modulation of the same SNPs on response, remission and other clinical features both in MDD patients and in a larger sample including 82 Bipolar Disorder (BD) patients as well. All patients were screened in the context of a European multicenter project. No association between both the investigated genes and treatment resistance and response was found in MDD patients. However, considering remission, higher rates of CREB1 rs889895 GG genotype were reported in MDD patients. Moreover, MAPK1 rs8136867 AG genotype was found to be associated with remission in the whole sample (MDD and BD). Present results suggest that some genetic polymorphisms in both CREB1 and MAPK1 could be associated with treatment remission. Although further research is needed to draw more definitive conclusions, such results are intriguing since suggest a potential role of two genes implicated in neuroplasticity and inflammatory processes in symptom remission after antidepressant treatment.

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.

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.

The premenstrual syndrome and fibromyalgia--similarities and common features.

The aim of the study was to assess the clinical similarities and common features of fibromyalgia syndrome (FM) and premenstrual dysphoric syndrome (PMDD). Thirty young patients who met the diagnostic criteria for PMDD were included in the study and compared to 26 women belonging to the medical staff of a general psychiatry department. All enrollees were interviewed and examined by a skilled physician. They completed the following nine survey items: demographic information, clinical health assessment questionnaire, fibromyalgia impact questionnaire, sleep and fatigue questionnaires, Sheehan disability scales, SF-36 assessment for quality of life, visual analog scale for pain, Mini International Neuropsychiatric Interview (MINI) questionnaire (assessment of coexistent psychiatric conditions), and the premenstrual severity scale. Additionally, each individual underwent a physical examination measuring the classical tender points and was asked to describe the distribution and continuum of her pain or tenderness. The PMDD group scored significantly higher in the measures pain and tenderness as well as in severity of premenstrual symptoms compared to the control group. Five patients in the PMDD group and none in the control group had FM. Quality of life measured by the SF-36 was higher in the control group than in the PMDD group and correlated with the degree of tenderness reported. Psychiatric comorbidity was significantly more common in the PMDD group, affecting 16 of the 30 PMDD patients compared to only three of the 26 control patients. In this study, patients with PMDD were found to have higher levels of tenderness, higher psychiatric comorbidity, greater level of physical disabilities, and a lower quality of life. These parameters were highly correlated with a lower pain threshold.

Anxiety and depression in patients with allergic and non-allergic cutaneous disorders.

Background  Numerous studies have shown that anxiety and depression are more prevalent among patients suffering from chronic skin disorders.

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.

Sex and Gender Differences in Autoimmune Diseases

Autoimmune and rheumatological diseases often come to mind when thinking about gender differences in medicine.