Publications by authors named "Cathrin Sauer"

33 Publications

Individuals at increased risk for development of bipolar disorder display structural alterations similar to people with manifest disease.

Transl Psychiatry 2021 Sep 20;11(1):485. Epub 2021 Sep 20.

Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.

In psychiatry, there has been a growing focus on identifying at-risk populations. For schizophrenia, these efforts have led to the development of early recognition and intervention measures. Despite a similar disease burden, the populations at risk of bipolar disorder have not been sufficiently characterized. Within the BipoLife consortium, we used magnetic resonance imaging (MRI) data from a multicenter study to assess structural gray matter alterations in N = 263 help-seeking individuals from seven study sites. We defined the risk using the EPIbipolar assessment tool as no-risk, low-risk, and high-risk and used a region-of-interest approach (ROI) based on the results of two large-scale multicenter studies of bipolar disorder by the ENIGMA working group. We detected significant differences in the thickness of the left pars opercularis (Cohen's d = 0.47, p = 0.024) between groups. The cortex was significantly thinner in high-risk individuals compared to those in the no-risk group (p = 0.011). We detected no differences in the hippocampal volume. Exploratory analyses revealed no significant differences in other cortical or subcortical regions. The thinner cortex in help-seeking individuals at risk of bipolar disorder is in line with previous findings in patients with the established disorder and corresponds to the region of the highest effect size in the ENIGMA study of cortical alterations. Structural alterations in prefrontal cortex might be a trait marker of bipolar risk. This is the largest structural MRI study of help-seeking individuals at increased risk of bipolar disorder.
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http://dx.doi.org/10.1038/s41398-021-01598-yDOI Listing
September 2021

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

CNS Drugs 2021 Aug 20;35(8):881-892. Epub 2021 Jul 20.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

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 = 0.11, p = 0.008; DBP: B = 0.21, SE = 0.08, 95% CI 0.06-0.36, p = 0.007; adjusted R = 0.08; p = 0.023).

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.
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http://dx.doi.org/10.1007/s40263-021-00837-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354966PMC
August 2021

Probabilistic Reversal Learning Deficits in Patients With Methamphetamine Use Disorder-A Longitudinal Pilot Study.

Front Psychiatry 2020 9;11:588768. Epub 2020 Dec 9.

Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.

Methamphetamine use disorder (MUD) is increasing worldwide and commonly associated with learning deficits. Little is known the about underlying trajectories, i.e., how the affected higher-order cognitive functions develop over time and with respect to abstinence and relapse. A probabilistic reversal learning (PRL) paradigm was implemented to uncover the microstructure of impulsive choice and maladaptive learning strategies in 23 patients with MUD in comparison with 24 controls. Baseline data revealed fewer optimal choices and a pattern of altered learning behavior from negative and positive feedback in patients suggesting impairments in flexibly-adapting behavior to changes of reward contingencies. Integrating longitudinal data from a follow-up assessment after 3 months of specific treatment revealed a group-by-time interaction indicating a normalization of these cognitive impairments in patients with MUD. In summary, our study demonstrates behavioral correlates of maladaptive decision-making processes in patients with MUD, which may recover after 3 months of MUD-specific therapy paving the way for further learning-based interventions. Limited by a small sample size, the results of this pilot study warrant replication in larger populations.
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http://dx.doi.org/10.3389/fpsyt.2020.588768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755887PMC
December 2020

Probabilistic Reversal Learning Deficits in Patients With Methamphetamine Use Disorder-A Longitudinal Pilot Study.

Front Psychiatry 2020 9;11:588768. Epub 2020 Dec 9.

Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.

Methamphetamine use disorder (MUD) is increasing worldwide and commonly associated with learning deficits. Little is known the about underlying trajectories, i.e., how the affected higher-order cognitive functions develop over time and with respect to abstinence and relapse. A probabilistic reversal learning (PRL) paradigm was implemented to uncover the microstructure of impulsive choice and maladaptive learning strategies in 23 patients with MUD in comparison with 24 controls. Baseline data revealed fewer optimal choices and a pattern of altered learning behavior from negative and positive feedback in patients suggesting impairments in flexibly-adapting behavior to changes of reward contingencies. Integrating longitudinal data from a follow-up assessment after 3 months of specific treatment revealed a group-by-time interaction indicating a normalization of these cognitive impairments in patients with MUD. In summary, our study demonstrates behavioral correlates of maladaptive decision-making processes in patients with MUD, which may recover after 3 months of MUD-specific therapy paving the way for further learning-based interventions. Limited by a small sample size, the results of this pilot study warrant replication in larger populations.
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http://dx.doi.org/10.3389/fpsyt.2020.588768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755887PMC
December 2020

Association of pro-inflammatory cytokines with clinical features in euthymic patients with Bipolar-I-Disorder.

J Affect Disord 2020 12 1;277:450-455. Epub 2020 Aug 1.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany. Electronic address:

Background: A chronic low-grade inflammatory state appears to be a relevant mechanism in the pathophysiology of bipolar disorder. Pro-inflammatory cytokines may influence disease course and individual symptomatology; and biological markers correlating with illness features may be of utility in clinical decision making during euthymia.

Methods: 51 euthymic outpatients with Bipolar-I-Disorder (BD-I) and 93 healthy controls (HC) were investigated. Comparisons between groups, and correlations with clinical features were performed. Serum concentrations of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and soluble interleukin-6 receptor (sIL-6R) were evaluated by ELISA under highly standardized conditions. Clinical features included duration of illness, number of previous suicide attempts and mood episodes (manic, hypomanic, depressive), scores of the Young Mania Rating Scale (YMRS), the Inventory of Depressive Symptoms (IDS-30), the Pittsburg Sleep Quality Index (PSQI), and the Global Assessment of Functioning (GAF).

Results: No significant difference in serum concentrations of IL-1β, TNF-α, and sIL-6R between BD-I euthymic patients and HC could be identified. Among euthymic BD-I patients, a positive correlation of r = 0.47 (p = 0.004) between levels of IL-1β and IDS-30 score was identified.

Limitations: The design was cross-sectional, most patients were receiving medication, only 3 cytokines were assessed, only euthymic BD-I patients were evaluated.

Conclusions: The findings suggest that elevated pro-inflammatory cytokine concentrations are likely state rather than trait markers of BD-I. It also seems unlikely that cytokine concentrations are clinically informative interepisode. An inflammatory component might possibly be involved in the pathophysiology of subsyndromic depression in BD-I, and conceivably of bipolar depression per se.
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http://dx.doi.org/10.1016/j.jad.2020.07.125DOI Listing
December 2020

Urothelial toxicity of esketamine in the treatment of depression.

Psychopharmacology (Berl) 2020 Nov 26;237(11):3295-3302. Epub 2020 Jul 26.

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany.

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.
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http://dx.doi.org/10.1007/s00213-020-05611-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561544PMC
November 2020

Improving early recognition and intervention in people at increased risk for the development of bipolar disorder: study protocol of a prospective-longitudinal, naturalistic cohort study (Early-BipoLife).

Int J Bipolar Disord 2020 Jul 1;8(1):22. Epub 2020 Jul 1.

Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.

Background: Bipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD.

Methods: Early-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15-35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPIbipolar) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD.

Discussion: Findings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.
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http://dx.doi.org/10.1186/s40345-020-00183-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326843PMC
July 2020

Familial risk of dementia and mediators of memory clinic referrals.

Psychogeriatrics 2020 09 24;20(5):790-791. Epub 2020 May 24.

Department of Psychiatry, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.

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http://dx.doi.org/10.1111/psyg.12566DOI Listing
September 2020

Prevalence of Prediabetes and Diabetes Mellitus Type II in Bipolar Disorder.

Front Psychiatry 2020 22;11:314. Epub 2020 Apr 22.

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital, Goethe University, Frankfurt, Germany.

Introduction: Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large.

Material And Methods: 85 bipolar disorder patients were recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort).

Results: Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration.

Discussion: When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.
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http://dx.doi.org/10.3389/fpsyt.2020.00314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188755PMC
April 2020

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

Australas Psychiatry 2020 08 15;28(4):386-390. Epub 2020 Mar 15.

Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.

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 ( = 65), MCI ( = 121), or dementia ( = 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, = 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.
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http://dx.doi.org/10.1177/1039856220908171DOI Listing
August 2020

Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study.

Bipolar Disord 2020 08 13;22(5):517-529. Epub 2020 Mar 13.

Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.

Objective: Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms.

Method: In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30 years were randomized to 14 weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample.

Results: Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs.

Conclusions: Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.
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http://dx.doi.org/10.1111/bdi.12894DOI Listing
August 2020

Melatonin suppression by melanopsin-weighted light in patients with bipolar I disorder compared to healthy controls

J Psychiatry Neurosci 2020 03;45(2):79-87

From the Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Ritter, Wieland, Pfennig, Weiss, Bauer, Severus, Sauer, Soltmann, Neumann); the Chair of Power Electronics, Institute of Electrical Power Engineering, TU Dresden (Wieland and Güldner); and the Department of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guilford, UK (Skene).

Background: Multiple lines of evidence suggest that the onset and course of bipolar disorder is influenced by environmental light conditions. Increased suppression of melatonin by light (supersensitivity) in patients with bipolar disorder has been postulated as an endophenotype by several studies. However, due to methodological shortcomings, the results of these studies remain inconclusive. This study investigated melatonin suppression in euthymic patients with bipolar I disorder using evening blue light specifically targeting the melanopsin system.

Methods: Melatonin suppression was assessed in euthymic patients with bipolar I disorder and healthy controls by exposure to monochromatic blue light (λmax = 475 nm; photon density = 1.6 × 1013 photons/cm2/s) for 30 minutes at 2300 h, administered via a ganzfeld dome for highly uniform light exposure. Serum melatonin concentrations were determined from serial blood sampling via radioimmunoassay. All participants received mydriatic eye drops and were genotyped for the PER3 VNTR polymorphism to avoid or adjust for potential confounding. As secondary outcomes, serum melatonin concentrations during dark conditions and after monochromatic red light exposure (λmax = 624 nm; photon density = 1.6 × 1013 photons/cm2/s) were also investigated. Changes in subjective alertness were investigated for all 3 lighting conditions.

Results: A total of 90 participants (57 controls, 33 bipolar I disorder) completed the study. Melatonin suppression by monochromatic blue light did not differ between groups (F1,80 = 0.56; p = 0.46). Moreover, there were no differences in melatonin suppression by monochromatic red light (F1,82 = 1.80; p = 0.18) or differences in melatonin concentrations during dark conditions (F1,74 = 1.16; p = 0.29). Healthy controls displayed a stronger increase in subjective alertness during exposure to blue light than patients with bipolar I disorder (t85 = 2.28; p = 0.027).

Limitations: Large interindividual differences in melatonin kinetics may have masked a true difference.

Conclusion: Despite using a large cohort and highly controlled laboratory conditions, we found no differences in melatonin suppression between euthymic patients with bipolar I disorder and healthy controls. These findings do not support the notion that supersensitivity is a valid endophenotype in bipolar I disorder.
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http://dx.doi.org/10.1503/jpn.190005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828907PMC
March 2020

Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms.

Int J Bipolar Disord 2019 Oct 4;7(1):21. Epub 2019 Oct 4.

Department of Psychiatry and Psychotherapy, Medical Faculty, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.

Background: Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression.

Methods: Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI).

Results: Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877).

Conclusions: This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839.
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http://dx.doi.org/10.1186/s40345-019-0155-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776578PMC
October 2019

Gender differences in the perception of cognitive decline.

Asian J Psychiatr 2019 Dec 23;46. Epub 2019 Sep 23.

Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.ajp.2019.09.011DOI Listing
December 2019

Melatonin suppression by melanopsin-weighted light in patients with bipolar I disorder compared to healthy controls

J Psychiatry Neurosci 2019 09 11;44(6):190005. Epub 2019 Sep 11.

From the Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (Ritter, Wieland, Pfennig, Weiss, Bauer, Severus, Sauer, Soltmann, Neumann); the Chair of Power Electronics, Institute of Electrical Power Engineering, TU Dresden (Wieland and Güldner); and the Department of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guilford, UK (Skene).

Background: Multiple lines of evidence suggest that the onset and course of bipolar disorder is influenced by environmental light conditions. Increased suppression of melatonin by light (supersensitivity) in patients with bipolar disorder has been postulated as an endophenotype by several studies. However, due to methodological shortcomings, the results of these studies remain inconclusive. This study investigated melatonin suppression in euthymic patients with bipolar I disorder using evening blue light specifically targeting the melanopsin system.

Methods: Melatonin suppression was assessed in euthymic patients with bipolar I disorder and healthy controls by exposure to monochromatic blue light (λmax = 475 nm; photon density = 1.6 × 1013 photons/cm2/s) for 30 minutes at 2300 h, administered via a ganzfeld dome for highly uniform light exposure. Serum melatonin concentrations were determined from serial blood sampling via radioimmunoassay. All participants received mydriatic eye drops and were genotyped for the PER3 VNTR polymorphism to avoid or adjust for potential confounding. As secondary outcomes, serum melatonin concentrations during dark conditions and after monochromatic red light exposure (λmax = 624 nm; photon density = 1.6 × 1013 photons/cm2/s) were also investigated. Changes in subjective alertness were investigated for all 3 lighting conditions.

Results: A total of 90 participants (57 controls, 33 bipolar I disorder) completed the study. Melatonin suppression by monochromatic blue light did not differ between groups (F1,80 = 0.56; p = 0.46). Moreover, there were no differences in melatonin suppression by monochromatic red light (F1,82 = 1.80; p = 0.18) or differences in melatonin concentrations during dark conditions (F1,74 = 1.16; p = 0.29). Healthy controls displayed a stronger increase in subjective alertness during exposure to blue light than patients with bipolar I disorder (t85 = 2.28; p = 0.027).

Limitations: Large interindividual differences in melatonin kinetics may have masked a true difference.

Conclusion: Despite using a large cohort and highly controlled laboratory conditions, we found no differences in melatonin suppression between euthymic patients with bipolar I disorder and healthy controls. These findings do not support the notion that supersensitivity is a valid endophenotype in bipolar I disorder.
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http://dx.doi.org/10.1503/jpn.190005DOI Listing
September 2019

Education correction for neurocognitive testing.

Psychogeriatrics 2020 03 5;20(2):237-238. Epub 2019 Aug 5.

Department of Psychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

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http://dx.doi.org/10.1111/psyg.12477DOI Listing
March 2020

[Folic acid and vitamin B12 determination in the assessment of cognitive disorders : Overview and data analysis from a university outpatient memory clinic].

Nervenarzt 2019 Nov;90(11):1162-1169

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.

Vitamin B12 and folic acid deficiencies are particularly frequent conditions in older people. Since these metabolic disorders represent relevant dyscognitive factors, the assessment of vitamin B12 and folic acid levels is essential in the diagnostic approach of cognitive disorders, such as mild cognitive impairment and dementia in an outpatient memory clinic. This article summarizes the relevant diagnostic and therapeutic aspects of vitamin B12 and folic acid deficiencies and their effects on cognition. The literature review is supplemented by a data analysis of a naturalistic cohort of 250 patients from this outpatient memory clinic.
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http://dx.doi.org/10.1007/s00115-019-0710-xDOI Listing
November 2019

[Analysis of risk factors, etiology and treatment standard of lithium poisoning].

Nervenarzt 2020 Jan;91(1):57-63

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.

Despite unlimited access to therapeutic drug monitoring lithium poisoning is still a common and potentially life-threatening but in most cases preventable complication of lithium treatment; however, it is still considered to be the gold standard in the treatment of affective disorders. The necessity of drug monitoring and potential lithium toxicity substantiate the skepticism of many therapists with respect to this often very effective treatment. This therefore limits the use of lithium although the unique therapeutic effects and high efficiency are well known. This retrospective data analysis of risk factors and etiology of lithium poisoning cases identified 58 cases of lithium poisoning, which were treated internally in this hospital between 2010 and 2014. Of the patients 67.2% were female and the majority were classified as chronic poisoning (66.1%). The most relevant patient-related risk factor seemed to be insufficient self-management as 26% of cases of lithium poisoning occurred during febrile infections or exsiccosis. Regarding practitioner-related risk factors, an insufficient consideration of drug interactions, insufficient therapeutic drug monitoring after dose increase and a paucity of experience and knowledge concerning lithium treatment were most relevant. This study illustrates the most important risk factors for lithium poisoning and their frequencies and contributes to raise awareness for this highly relevant topic. These data can help to prevent further cases of lithium poisoning. Furthermore, the results enable a comparison between the actual treatment reality and currently available evidence for the treatment of lithium poisoning.
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http://dx.doi.org/10.1007/s00115-019-0705-7DOI Listing
January 2020

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

Early Interv Psychiatry 2019 10 10;13(5):1165-1172. Epub 2018 Oct 10.

Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus, Medical Faculty, Technische Universität Dresden, Dresden, Germany.

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.
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http://dx.doi.org/10.1111/eip.12748DOI Listing
October 2019

Role of the IL-6-Receptor expression in CD14+ monocytes in modulating sleep in patients with bipolar disorder.

J Affect Disord 2018 10 25;239:152-160. Epub 2018 Jun 25.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Objective: Bipolar disorder is a severe mental disorder associated with persistent sleep disturbances and elevated levels of mRNA coding for pro-inflammatory cytokines within peripheral monocytes. The mechanisms causing and sustaining a reduced sleep quality remain elusive. The pro-inflammatory cytokine receptor IL-6R is known to negatively affect sleep quality and architecture. Since elevations in IL-6R have repeatedly been demonstrated in bipolar disorder the association of sleep quality and architecture with levels of mRNA coding for IL-6R in monocytes was to be tested.

Methods: Euthymic patients with bipolar disorder (n = 24) and healthy control subjects (n = 25) were assessed using all night polysomnography (PSG) and six day actigraphy. CD14+ monocytes were isolated on the evening of PSG assessment and levels of mRNA coding for IL-6R and other cytokines were determined using hybridization based assays. Interactions between IL-6R and sleep measures were calculated using linear regression models, adjusting for potential confounders.

Results: Patients with bipolar disorder were found to have a reduced subjective sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) and more frequent arousals and short changes to wake during sleep. Both PSQI and the frequency of arousals were significantly predicted by levels of IL-6R. Contrary to previous publications, elevated levels of mRNA coding for pro-inflammatory cytokines in peripheral CD14+ monocytes of patients with bipolar disorder could not be replicated.

Limitations: Participants were only investigated with one night of PSG which may have given rise to first night effects.

Conclusions: Reduced sleep quality in euthymic patients with bipolar disorder may be related to an increased expression of IL-6R by peripheral monocytes.
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http://dx.doi.org/10.1016/j.jad.2018.06.037DOI Listing
October 2018

A Novel Study Design to Systematically Explore the Impact of Trial Methodology on Psychopharmacological Treatment Outcome in Patients with Depression.

Pharmacopsychiatry 2019 Jul 5;52(4):170-174. Epub 2018 Jul 5.

Privat-Nervenklinik Dr. Med. Kurt Fontheim, Liebenburg, Germany.

Introduction: Randomized, double-blind, placebo-controlled trials were developed to draw rather unbiased conclusions regarding the efficacy of antidepressants in the treatment of a major depressive episode (internal validity), mostly with the purpose of formal approval of new compounds in this indication. However, at the same time, data suggest that the very process of randomization and blinded administrations of placebo will have a significant impact on the efficacy of the antidepressant tested and therefore may limit the external validity of results obtained from this type of studies. Therefore, there is an urgent need to systematically study the impact of randomization/placebo control/blinding on patient population, efficacy, tolerability, and external validity in the psychopharmacological treatment of patients with a major depressive episode.

Methods: To develop a study design that allows the systematic exploration of the impact of trial design on characteristics of included patient population and outcome.

Results: We propose a study design including sample size calculation and statistical analysis in which patients with a major depressive episode are randomized to 3 distinct study designs that differ with regard to control, randomization, and blindness.

Discussion: The results of the proposed study design may have substantial consequences when it comes to how to best interpret the results of traditional randomized, double-blind, placebo-controlled trials in the acute treatment of major depressive disorder. Furthermore, they may lead to the implementation of new study designs that may be more suitable for assessing the effectiveness of new antidepressant compounds in everyday clinical practice.
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http://dx.doi.org/10.1055/a-0643-4796DOI Listing
July 2019

Long-term treatment with supraphysiologic doses of levothyroxine in treatment-refractory mood disorders - A prospective study of cardiovascular tolerability.

J Affect Disord 2018 10 30;238:213-217. Epub 2018 May 30.

Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany. Electronic address:

Background: To investigate long-term effects of adjunctive prophylactic treatment with supraphysiologic doses of levothyroxine (L-T4) on cardiovascular tolerability in 23 patients with treatment-refractory mood disorders.

Methods: Starting point for a comprehensive cardiovascular assessment in patients was the indication for long-term maintenance treatment with L-T4 (mean dose 463 mcg/day). Prospective longitudinal assessment of the cardiovascular risk profile included in addition to a physical examination and blood pressure measurement, several technical investigations: resting electrocardiogram, transthoracic echocardiogram, cardiac stress test, and holter electrocardiogram. Statistical analysis was performed by linear mixed effects models (LMM) for evaluation of longitudinal changes in various heart measures.

Results: During the mean observational period of 20.4 months none of the heart measures reached statistical significance in change over time. None of the assessed cardiac parameters of each single patient was in a range predictive for cardiac dysfunction.

Limitations: Small sample size, no technical cardiac investigations prior to L-T4 initiation, no patient control group with mood disorders who did not receive L-T4.

Conclusions: Results of this study indicated no increased risk for cardiovascular disorders during treatment with supraphysiologic L-T4 doses in patients with refractory mood disorders.
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http://dx.doi.org/10.1016/j.jad.2018.05.034DOI Listing
October 2018

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

Sleep Disord 2016 6;2016:4031535. Epub 2016 Nov 6.

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.

. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. . To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. . 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 -tests and corrected for multiple comparisons. . Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. . 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.
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http://dx.doi.org/10.1155/2016/4031535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116328PMC
November 2016

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

Sleep Disord 2016 6;2016:4031535. Epub 2016 Nov 6.

Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany.

. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. . To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. . 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 -tests and corrected for multiple comparisons. . Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. . 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.
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http://dx.doi.org/10.1155/2016/4031535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116328PMC
November 2016

Type 2 diabetes and pre-diabetic abnormalities in patients with bipolar disorders.

J Affect Disord 2016 Jan 28;189:240-5. Epub 2015 Sep 28.

Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Germany. Electronic address:

Background: Abnormalities in the glucose metabolism cause nervous and organic damage and are a cardiovascular risk factor. They could be a main cause for the increased morbidity and mortality rates found in patients with bipolar disorders. The exact prevalence of diabetes and pre-diabetic abnormalities, however, is not clear.

Methods: 85 euthymic outpatients with bipolar disorders from two university hospitals in Germany underwent an oral glucose tolerance test, laboratory screening and clinical measurements. Socio-demographic data, medication, severity of illness, global functioning and life quality were assessed.

Results: Diabetes mellitus was found in 7% of the patients, pre-diabetic abnormalities in 27%. The group of patients with abnormalities in the glucose metabolism had significantly lower quality of life and global functioning. Higher BMI, leptin, triglycerides and CRP levels significantly increased the likelihood for pre-diabetes/diabetes.

Limitations: The low sample size did only allow limited assessment of impact of medication on the results. No healthy controls were assessed.

Conclusions: One-third of the patients with bipolar disorders showed abnormalities in the glucose metabolism and this was associated with impaired global functioning and lower quality of life. Early detection and intervention strategies fitting the needs of patient with bipolar disorder are needed to improve both physical and mental health.
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http://dx.doi.org/10.1016/j.jad.2015.09.041DOI Listing
January 2016

Prophylactic lithium treatment and cognitive performance in patients with a long history of bipolar illness: no simple answers in complex disease-treatment interplay.

Int J Bipolar Disord 2014 24;2. Epub 2014 Dec 24.

Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany ; International Group for the Study of Lithium-Treated Patients (IGSLi), Berlin, Germany.

Cognitive impairment in patients with bipolar disorder (BD) is not restricted to symptomatic phases. It is also present in euthymia. There is evidence of differences in the brain's structure between bipolar patients and healthy individuals, as well as changes over time in patients. Lithium constitutes the gold standard in long-term prophylactic treatment. Appropriate therapy that prevents new episodes improves the disease's course and reduces the frequency of harmful outcomes. Interestingly, preclinical data suggest that lithium has a (additional) neuroprotective effect. There is limited data on its related effects in humans and even less on its long-term application. In this multi-center cross-sectional study from the International Group for the Study of Lithium-treated Patients (IGSLi), we compared three groups: bipolar patients without long-term lithium treatment (non-Li group; <3 months cumulative lithium exposure, ≥24 months ago), bipolar patients with long-term lithium treatment (Li group, ongoing treatment ≥24 months), and healthy subjects (controls). Strict inclusion and exclusion criteria were defined; the inclusion criteria for patients were diagnosis of BD types I or II, duration of illness ≥10 years, ≥5 episodes in patient's history and a euthymic mood state. Neurocognitive functioning was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the California Verbal Learning Test (CVLT), and a visual backward masking (VBM) task. A total of 142 subjects were included, 31 in the non-Li and 58 in the Li group, as well as 53 healthy controls. Treated patients with long-standing BD and controls did not differ significantly in overall cognitive functioning and verbal learning, recall, and recognition; regardless of whether lithium had been part of the treatment. Patients, however, demonstrated poorer early visual information processing than healthy controls, with the lithium-treated patients performing worse than those without. Our data suggest that bipolar patients with a long illness history and effective prophylactic treatment do not reveal significantly impaired general cognitive functioning or verbal learning and memory. However, they are worse at processing early visual information. Accompanying volumetric and spectroscopic data suggest cell loss in patients not treated with lithium that may be counterbalanced by long-term lithium treatment.
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http://dx.doi.org/10.1186/s40345-014-0016-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275548PMC
December 2014

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

Int J Bipolar Disord 2014 20;2:15. Epub 2014 Dec 20.

Department of Psychiatry, University of Oxford, Oxford, UK.

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.
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http://dx.doi.org/10.1186/s40345-014-0015-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272359PMC
December 2014

Supraphysiologic doses of levothyroxine as adjunctive therapy in bipolar depression: a randomized, double-blind, placebo-controlled study.

J Clin Psychiatry 2014 Feb;75(2):162-8

Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin.

Objective: Suboptimal availability of circulating thyroid hormones may contribute to the high rate of treatment failures in bipolar disorder. This study tested the efficacy of adjunctive treatment with supraphysiologic doses of levothyroxine in patients with bipolar depression and the hypothesis that women would display a better outcome compared to men.

Method: The aims of this multicenter, 6-week, double-blind, randomized, placebo-controlled fixed-dose (300 μg/d) trial conducted from 2004 to 2009 were to assess efficacy and tolerability of levothyroxine adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication for patients with bipolar I or II disorder, currently depressed (DSM-IV), and to investigate gender differences in treatment response. The primary efficacy variable was mean change in Hamilton Depression Rating Scale (HDRS) score.

Results: Of 74 patients enrolled in the study, 62 (35 with bipolar I; mean age = 44.9 years) were randomized. Mean change in HDRS score from randomization to week 6 was larger in the levothyroxine group compared to the placebo group, with a 2.7-point difference (decline of -7.8 [38.3%] vs -5.1 [25.5%]; last-observation-carried-forward analysis). The course of HDRS scores over time from randomization to week 6 was significantly different between groups at week 4 (P = .046) but not at the end of the placebo-controlled phase (P = .198). The secondary analysis of women (n = 32) revealed a significant difference between groups in mean change in HDRS score (-16.6% placebo vs -42.4% levothyroxine, P = .018). A mixed-effects model for repeated-measures analysis showed a significant between-group difference in HDRS score (6.8, P = .012) for women. High thyroid-stimulating hormone levels, indicating suboptimal levels of circulating thyroid hormones, were predictive for positive treatment outcome in women treated with levothyroxine in a linear regression model (F3 = 3.47; P = .05).

Discussion: This trial demonstrated that patients treated with levothyroxine did numerically better than those treated with placebo; however, the study failed to detect a statistically significant difference between the 2 groups in the primary outcome measure due to a high placebo response rate. Previous findings that women show better improvement in depression scores with levothyroxine compared to men were confirmed.

Trial Registration: ClinicalTrials.gov identifier: NCT01528839.
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http://dx.doi.org/10.4088/JCP.12m08305DOI Listing
February 2014

Cardiovascular risk and hippocampal thickness in Alzheimer's disease.

Int J Alzheimers Dis 2013 21;2013:108021. Epub 2013 Oct 21.

Department of Psychiatry and Psychotherapy, Division of Old Age Psychiatry and Cognitive Neuropsychiatry, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany ; German Center for Neurodegenerative Diseases (DZNE), 01307 Dresden, Germany.

Cardiovascular risk factors influence onset and progression of Alzheimer's disease. Among cognitively healthy people, changes in brain structure and function associated with high blood pressure, diabetes, or other vascular risks suggest differential regional susceptibility to neuronal damage. In patients with Alzheimer's disease, hippocampal and medial temporal lobe atrophy indicate early neuronal loss preferentially in key areas for learning and memory. We wanted to investigate whether this regional cortical thinning would be modulated by cardiovascular risk factors. We utilized high-resolution magnetic resonance imaging and a cortical unfolding technique to determine the cortical thickness of medial temporal subregions in 30 patients with Alzheimer's disease. Cardiovascular risk was assessed using a sex-specific multivariable risk score. Greater cardiovascular risk was associated with cortical thinning in the hippocampus CA2/3/dentate gyrus area but not other hippocampal and medial temporal subregions. APOE genotype, a family history of Alzheimer's disease, and age did not influence cortical thickness. Alzheimer's disease-related atrophy could mask the influence of genetic risk factors or age on regional cortical thickness in medial temporal lobe regions, whereas the impact of vascular risk factors remains detectable. This highlights the importance of cardiovascular disease prevention and treatment in patients with Alzheimer's disease.
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http://dx.doi.org/10.1155/2013/108021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3818844PMC
November 2013

APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging and Alzheimer's disease.

Psychiatry Res 2013 Dec 27;214(3):212-20. Epub 2013 Sep 27.

Department of Psychiatry and Psychotherapy, Division of Old Age Psychiatry and Cognitive Neuropsychiatry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany; DZNE, German Center for Neurodegenerative Diseases, Dresden, Germany. Electronic address:

Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimer's disease, associated with regionally specific effects on brain morphology and function during the life span. Furthermore, entorhinal and hippocampal hemispheric asymmetry could be modified by pathology during Alzheimer's disease development. Using high-resolution magnetic resonance imaging and a cortical unfolding technique we investigated whether carrying the APOE-4 allele influences hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients with Alzheimer's disease as well as in middle-aged and older cognitively healthy individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left hemisphere when compared with the right hemisphere across all participants. Non-carriers of the allele showed this asymmetry only in the patient group. Cortical thickness in the hippocampus did not vary between hemispheres among APOE-4 allele carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in entorhinal cortical thickness. Among Alzheimer's disease patients, this asymmetry might be less dependent on the APOE genotype and a more general marker of incipient disease pathology.
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http://dx.doi.org/10.1016/j.pscychresns.2013.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851589PMC
December 2013
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