Impact of cognitive reserve on clinical and neuropsychological measures in patients with mild cognitive impairment

Objective: Cognitive reserve influences age of onset, speed of progression, and clinical manifestations of Alzheimer’s disease. We investigated whether cognitive reserve interacts with clinical and neuropsychological parameters in mild cognitive impairment (MCI). Methods: In this cross-sectional study, we recruited 273 people (70.6 ± 10.1 years, 54.6% women) suffering from subjective memory complaints (n = 65), MCI (n = 121), or dementia (n = 87). Patients underwent neuropsychological evaluation, laboratory testing, and brain imaging. Additionally, we obtained information on years of education and help-seeking motivation. Results: MCI patients with a university degree were significantly older than those without (71.6 ± 9.6 vs. 66.9 ± 10.3, p = 0.02). University-educated MCI patients demonstrated superior performance in verbal fluency. Intrinsic help-seeking motivation (self-referral) was associated with higher cognitive reserve. Female MCI patients presented with greater intrinsic motivation. Conclusion: Cognitive reserve modulates clinical and neuropsychological measures in patients with MCI

Lithium for prevention of mood episodes in bipolar disorders:systematic review and meta-analysis

BACKGROUND: In a previous meta-analysis of randomized controlled trials comparing lithium with placebo as a long-term treatment in bipolar disorders, we observed a clear preventative effect for manic episodes; however, the effect was equivocal for depressive episodes. Since then, the evidence base has grown further. In this update, we furthermore present the data on efficacy of lithium in comparison to alternative drug treatments. In addition, we analyze the data comparing lithium with placebo and other treatments regarding drop-outs due to reasons other than a mood episode and completion of study (no mood episode and no drop-out to reasons other than a mood episode). METHODS: Randomized controlled trials (RCTs) were sought comparing lithium with placebo and lithium with an alternative treatment in bipolar disorders where the stated intent of treatment was prevention of mood episodes. To this purpose, the Cochrane Central Register of Controlled Trials (CENTRAL) was searched. Reference lists of relevant papers and major textbooks of mood disorders were examined. Authors, other experts in the field, and pharmaceutical companies were contacted for knowledge of suitable trials, published or unpublished. RESULTS: For the comparison of lithium with placebo, seven trials (1,580 participants) were included. Lithium was more effective than placebo in preventing overall mood episodes (random effects RR 0.66, 95% CI 0.53 to 0.82), manic episodes (random effects RR 0.52, 95% CI 0.38 to 0.71), and, dependent on the type of analyses applied, depressive episodes (random effects RR 0.78, 95% CI 0.59 to 1.03; fixed effect RR 0.73, 95% CI 0.60 to 0.88). Lithium was inferior to placebo in leading to drop-outs for reasons other than a mood episode (random effects RR 1.33, 95% CI 1.07 to 1.65) but superior to placebo on study completion (random effects RR 1.69, 95% CI 1.12 to 2.55). For the comparison of lithium with anticonvulsants, seven trials were included (n = 1,305). In prevention of manic episodes, lithium showed superiority compared to anticonvulsants (random effects RR 0.66, 95% CI 0.44 to 1.00). However, there was no significant difference regarding prevention of overall mood episodes, depressive episodes, dropping-out to reasons other than a mood episode, or study completion. CONCLUSIONS: The evidence base for lithium in the long-term treatment of bipolar disorders has strengthened. With no other drug available having such ample and consistent evidence for its efficacy lithium remains the most valuable treatment option in this indication

Urothelial toxicity of esketamine in the treatment of depression

Rationale!#!Ketamine is the first widely used substance with rapid-onset antidepressant action. However, there are uncertainties regarding its potential urothelial toxicity, particularly after repeated application. In the context of rising recreational ketamine use, severe side effects affecting the human urinary tract have been reported. It is assumed that ketamine interacts with bladder urothelial cells and induces apoptosis.!##!Objectives!#!This study aimed to assess whether single or repeated doses of esketamine used in an antidepressant indication are associated with urinary toxicity.!##!Methods!#!We included male and female inpatients with a current episode of depression and a diagnosis of recurrent depressive disorder, bipolar disorder or schizoaffective disorder according to ICD-10 criteria (n = 25). The esketamine treatment schedule involved a maximum of 3× weekly dosing at 0.25-0.5 mg/kg i.v. or s.c. The primary outcome was the change in urine toxicity markers (leukocytes, erythrocytes, protein and free haemoglobin). Description of demographic, clinical and laboratory data was conducted using means, standard deviations, frequencies and percentages. Changes in urinary toxicity markers over time were evaluated using linear mixed models with gender as a covariate.!##!Results!#!The participants received an average of 11.4 (SD 8) esketamine treatments, and an average number of 11.2 (SD 8) urine samples were analysed over the course of treatment. Neither urinary leukocyte concentration (F(20; 3.0) = 3.1; p = 0.2) nor erythrocyte concentration (F(20;2.2) = 4.1; p = 0.2) showed a significant trend towards increase during the course of esketamine treatment. Similarly, free haemoglobin and protein concentrations, which were analysed descriptively, did not display a rise during treatment. There was a significant improvement in depression ratings after esketamine treatment (p < 0.001).!##!Conclusions!#!This study is, to the best of our knowledge, the first to focus on urothelial toxicity of esketamine used in antidepressant indication and dose. The results indicate that the use of single or repeated doses of esketamine is unlikely to cause urothelial toxicity. The results are in need of confirmation as sample size was small

Comparison of Subjective and Objective Sleep Estimations in Patients with Bipolar Disorder and Healthy Control Subjects

Background. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. Study Objectives. To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. Methods. Actimetry was used to assess sleep latency and duration in 49 euthymic participants (bipolar = 21; healthy controls = 28) for 5–7 days. Participants simultaneously recorded estimated sleep duration and sleep latency on a daily basis via an online sleep diary. Group differences in the discrepancy between subjective and objective parameters were calculated using t-tests and corrected for multiple comparisons. Results. Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone in patients with bipolar disorders may systematically underestimate sleep duration compared to healthy controls. The additional use of objective assessment methods such as actimetry is advisable

Cardiovascular Effects of Combining Subcutaneous or Intravenous Esketamine and the MAO Inhibitor Tranylcypromine for the Treatment of Depression:A Retrospective Cohort Study

Background!#!(Es)ketamine and monoamine oxidase inhibitors (MAOIs), e.g., tranylcypromine, are therapeutic options for treatment-resistant major depression. Simultaneous administration is currently not recommended because of concern about hypertensive crises.!##!Objective!#!Our objective was to evaluate whether changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) during esketamine administration differed between patients who concomitantly received tranylcypromine and those who did not.!##!Methods!#!This was a retrospective cohort study utilizing cardiovascular monitoring data from inpatients treated for severe depression in unipolar, bipolar, and schizoaffective disorder. Primary outcomes were change in mean BP and HR during the first hour after intravenous or subcutaneous esketamine administration compared with baseline, controlled for confounders. Secondary analyses quantify differences in absolute BP during esketamine treatment and comparisons of BP peaks, temporal effects, and intraindividual comparisons before and after tranylcypromine initiation.!##!Results!#!Our analysis included 509 esketamine administrations in 43 patients, 14 of whom concomitantly received tranylcypromine. Controlling for creatinine and age, mean ± standard deviation (SD) BP changes were significantly increased by concomitant tranylcypromine treatment (ΔSBP: F[1,503] = 86.73, p < 0.001; ΔDBP: F[1,503] = 55.71, p < 0.001), but HR remained unaffected. Mean SBP change during esketamine administration was 2.96 ± 18.11 mmHg in patients receiving tranylcypromine (TCP+) and -8.84 ± 11.31 mmHg in those who did not (TCP-). Changes in DBP were -2.81 ± 11.20 mmHg for TCP+ and -10.77 ± 9.13 mmHg for TCP-. Moreover, we found a significant dose-response relationship between tranylcypromine dose and BP (SBP: B = 0.35, standard error [SE] = 0.12, 95% confidence interval [CI] 0.12-0.60, p = 0.004; adjusted R!##!Conclusions!#!Although statistically significant changes in BP were identified in patients receiving tranylcypromine and esketamine, these changes were clinically insignificant. Thus, combining esketamine and this MAOI appears to be safe at standard doses. The dose-response relationship calls for caution with higher doses of tranylcypromine

Suicide risk after psychiatric discharge: study protocol of a naturalistic, long-term, prospective observational study

Background!#!Suicide risk of psychiatric patients has proven to be strongly increased in the months after discharge from a psychiatric hospital. Despite this high risk, there is a lack of systematic research on the causes of this elevated suicide risk as well as a lack of treatment and intervention for patients at high risk after discharge. The main objective of this pilot study is, firstly, to examine the factors contributing to the elevated !##!Methods!#!In this multi-centre pilot study, treatment as usual is complemented by an additional 18-month post-discharge setting of care for psychiatric patients at high risk for suicide. Two groups of patients differing in the amount of post-discharge personal contacts will be compared. One group of patients will be offered continuous personal contacts after discharge (months 1-6: monthly contacts; months 6-18: every 2 months) while another group of patients will receive contacts only at months 6, 12, and 18 after discharge. Data on suicidality, as well as associated with other symptoms, treatment, and significant events, will be collected. In the case of health-related severe events, the setting of care allows the patient to have the opportunity to connect with the doctor or therapist treating the patient.!##!Discussion!#!The results of this study will contribute to identifying critical factors raising suicide risk after discharge and will demonstrate the potential influence on suicide prevention of a setting of care with regular personal contact after discharge.!##!Trial registration!#!ZMVI1-2517FSB135 - funded by the German Federal Ministry of Health

Comparison of biomechanical properties in ascending aortic aneurysms of patients with congenital bicuspid aortic valve and Marfan syndrome

Item does not contain fulltex

Creativity in persons at-risk for bipolar disorder-A pilot study

Aim The association between bipolar disorder and creativity may be related to symptoms of the disorder itself or personality traits present before the onset. To further explore the relationship between creativity and clinical risk for bipolar disorder, creativity among individuals with a history of depressive disorder and varying risk for future (hypo-)manic episodes was assessed and compared. Methods Thirty-eight participants completed the diagnostic process, including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Diagnosis, Hamilton Depression Scale and Young Mania Rating Scale. The early detection tools Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P), Early Phase Inventory for Bipolar Disorders (EPIbipolar) and bipolar-at-risk-(BAR) criteria were used to assign participants into different at-risk groups. Assessment of creativity included Barron-Welsh Art Scale (BWAS) and Creative Achievement Questionnaire (CAQ). Scores were compared between low- and high-risk groups for the development of bipolar disorder. Results Participants meeting BAR criteria scored significantly higher on the BWAS than the non-BAR group (P = 0.03). EPIbipolar groups did not differ significantly in creativity scores. Participants with mood swings, especially when associated with increased activity and euphoric features, had significantly higher BWAS scores compared to individuals without mood swings (P = 0.04). Sleep disturbances, substance abuse, anxiety, ADHD and behavioural disturbances in childhood or adolescence had no effect on creativity level or achievement scores. Generalisability was reduced by small sample size and inclusion of depressive participants only considered at-risk for bipolar disorder. Conclusions There is evidence of increased creativity, but not of higher creative achievements, in persons at-risk of bipolar disorder. Mood swings are strongly associated with creativity