[Show abstract][Hide abstract] ABSTRACT: Careful observation of the longitudinal course of bipolar disorders is pivotal to finding optimal treatments and improving outcome. A useful tool is the daily prospective Life-Chart Method, developed by the National Institute of Mental Health. However, it remains unclear whether the patient version is as valid as the clinician version.
[Show abstract][Hide abstract] ABSTRACT: Objectives
The impact of Hatha yoga as add-on treatment to quetiapine fumarate extended release (QXR) or escitalopram (ESC) in depressed patients on hypothalamic-pituitary-adrenal (HPA) axis activity was assessed.
60 inpatients suffering from major depressive disorder (MDD) according to DSM-IV were randomized for a 5 week treatment with Yoga or not (control group) and with either QXR (300 mg/day) or ESC (10 mg/day). Serial dexamethasone/corticotropin releasing hormone (DEX/CRH) tests were performed to assess HPA axis function. The Hamilton Depression Rating Scale (21-HAMD) was used weekly.
A more pronounced down regulation of the HPA axis activity due to yoga could not be detected. The stepwise long term cortisol reduction was seen in both medication groups, irrespectively of yoga add-on treatment. In addition, cortisol improvers in week 1 of therapy (reduction in cortisol peak value within the DEX/CRH test) reached significant greater amelioration of depressive symptoms after 5 weeks.
Our results suggest that antidepressant agents down regulate HPA axis function to a greater extent than additional Hatha yoga treatment. Moreover, an early reduction of HPA system hyperactivity after one week of pharmacological treatment seems to raise the possibility of a favorable treatment response.
Journal of Psychiatric Research 01/2014; · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Targeted high-throughput sequencing of many amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) genes in parallel has the potential to reveal novel ALS- and/or FTD-phenotypes and to provide missing links on the ALS-FTD continuum. For example, although the 43-kDa transactive response DNA binding protein is the major pathologic hallmark linking ALS and FTD, mutations in the gene encoding 43-kDa transactive response DNA binding protein (TARDBP) have been appreciated only as a cause of ALS-phenotypes, but not yet of pure FTD. Thus, the genetic link is not yet well substantiated that TARDBP mutations can cause the full spectrum of the ALS-FTD continuum. High-throughput sequencing of 18 ALS and FTD genes in an index patient presenting with early-onset pure (behavioral) FTD and a positive family history for ALS revealed an established TARDBP mutation, A382T. This finding demonstrates that a TARDPB mutation can cause early-onset pure FTD without evidence for ALS even in advanced FTD disease stages. Moreover, it indicates that TARDPB screening might be considered even in young patients with "pure" neuropsychiatric disturbances and without evidence of neurodegenerative disease in the parental generation.
Neurobiology of aging 10/2013; · 5.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ~40%-50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood.
The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls.
We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04).
The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders.
PLoS ONE 01/2012; 7(7):e40479. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent published data and treatment guidelines have created uncertainty about the use of lamotrigine in affective disorders, especially in acute bipolar depression. Furthermore, unpublished data on lamotrigine in mania, mixed episodes, unipolar depression and rapid cycling are still waiting to be integrated into the literature. Therefore, we critically reviewed the position of lamotrigine in the acute and long-term treatment of affective disorders. Studies were identified by searching English language articles published in MEDLINE using the key words: lamotrigine, bipolar depression, unipolar depression, mania, mixed episode, long-term treatment, rapid-cycling. Results of unpublished trials were obtained from the GlaxoSmithKline website. Lamotrigine showed efficacy in the prophylaxis of bipolar disorder, more so in depressive than manic episodes. There was no evidence of effectiveness in the acute treatment of mania, mixed episodes, unipolar depression or rapid-cycling bipolar I disorder. Its effect in the acute treatment of bipolar depression is at most small. Based on current evidence, lamotrigine is indicated for the prophylaxis of bipolar disorder with predominantly depressive episodes. Its effectiveness in the acute treatment of bipolar depression is open to debate, and practical considerations limit its usefulness here. There are no grounds for recommending its use in manic or mixed states, in rapidly-cycling bipolar I or in unipolar depression.
Journal of Psychopharmacology 10/2011; 25(10):1289-94. · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorders are often not recognized. Several screening tools have been developed, e.g., the Hypomania Checklist-32 (HCL-32) and the Mood Disorder Questionnaire (MDQ) to improve this situation. Whereas the German HCL-32 has been used in non-clinical samples, neither the HCL-32 nor the MDQ has been validated in German samples of mood-disordered patients. Additionally, hardly any prior study has included patients with non-mood disorders or has considered potential effects of comorbid conditions. Therefore the goal of this study was to test the validity of both scales in a diverse patient sample while also taking into account psychiatric comorbidity.
A multi-site study was conducted involving seven centers. Patients (n=488) completed the HCL-32 and MDQ and were independently interviewed with the Structured Clinical Interview for DSM (SCID).
Sensitivity for bipolar I was similar for HCL-32 and MDQ (.88 and .84) but slightly different for bipolar II (.90 and .83), specificity, however, was higher for MDQ. In general, a comorbid condition led to increased scores in both tools regardless of whether the primary diagnosis was bipolar or not. LIMITATIONS AND DISCUSSION: Although we included not just mood-disordered patients, detailed subgroup analyses for all diagnostic categories were not possible due to sample sizes. In summary, HCL-32 and MDQ seem fairly comparable in detecting bipolar disorders although their effectiveness depends on the goal of the screening, psychiatric comorbidity, and potentially the setting.
Journal of affective disorders 02/2011; 128(3):291-8. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Electroconvulsive Therapy (ECT) is a powerful treatment option in severe or chronic catatonic states and has been reported to be useful in oligophrenic patients. We report the followup medical history of a patient with corpus callosum aplasia (or agenesis) who was continuously treated with ECT over three years. First, he improved considerably after a series of ECT, but relapses of catatonia made a continuous, weekly ECT necessary. Due to the severity of the brain malformation, an add-on medication with benzodiazepines and second generation antipsychotics was necessary to treat catatonic symptoms. This case emphasises the benefits of long-term ECT in oligophrenic patients.
[Show abstract][Hide abstract] ABSTRACT: Cardiovascular disease (CVD) and major depressive disorder (MDD) are frequent worldwide and have a high comorbidity rate. Omega-3 fatty acids have been suggested as disease modulators for both CVD and MDD. Therefore, we studied whether polyunsaturated fatty acids and the Omega-3 Index may represent markers for assessment of the cardiovascular risk in somatically healthy patients suffering from MDD.
We conducted a case-control study from July 2004 to December 2007 in 166 adults (86 inpatients with MDD but without CVD from the Department of Psychiatry and Psychotherapy and 80 age- and sex-matched healthy controls from an outpatient clinic of the Division of Preventive Cardiology, Ludwig Maximilian University of Munich, Germany). Information gathered at baseline included MDD diagnosis according to DSM-IV criteria, depression ratings, conventional cardiovascular risk factors, and fatty acid and interleukin-6 determinations. Fatty acid composition was analyzed according to the HS-Omega-3 Index methodology. During the study, patients received no supplementation with omega-3 fatty acids. The main inclusion criteria were the diagnosis of MDD according to DSM-IV and a 17-item Hamilton Depression Rating Scale (HDRS-17) score of at least 17. Treatment response and remission were defined using the HDRS-17.
Several conventional risk factors such as high triglyceride (mean, 152 mg/dL vs 100 mg/dL; P < .001) and fasting glucose (mean, 96 mg/dL vs 87 mg/dL; P = .005) values as well as greater waist circumference (mean, 97 cm vs 87 cm; P = .019) and higher body mass index (calculated as kg/m(2); mean, 26 vs 24; P = .011) were more prevalent in MDD patients in comparison with controls. The Omega-3 Index (mean, 3.9% vs 5.1%; P < .001) and individual omega-3 fatty acids were significantly lower in MDD patients. An Omega-3 Index < 4% was associated with high concentrations of the proinflammatory cytokine interleukin-6 (χ(2) = 7.8, P = .02).
Conventional cardiovascular risk factors, the Omega-3 Index, and interleukin-6 levels indicated an elevated cardiovascular risk profile in MDD patients currently free of CVD. Our results support the employment of strategies to reduce the cardiovascular risk in still cardiovascularly healthy MDD patients by targeting conventional risk factors and the Omega-3 Index.
The Journal of Clinical Psychiatry 12/2010; 72(9):1242-7. · 5.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet.
In this prospective, double-blind, placebo-controlled, randomized trial, 23 inpatients with bipolar depression according to DSM-IV criteria were included. Before randomization, patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week. After inclusion, all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks. The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale (HDRS) within 6 weeks.
After 6 weeks of treatment, the HDRS score decreased in both groups. There was no significant difference between both the groups at any point of time with respect to the HDRS.
Derived from this small pilot study, adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression. However, this lack of additional benefit seems to stem from the already good effectiveness of the control group, namely the treatment with citalopram.
Human Psychopharmacology Clinical and Experimental 03/2010; 25(2):126-32. · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study aimed to increase the knowledge about the detailed course differences between different forms of bipolar disorder.
Using the prospective life-chart-clinician version, we compared the fine-grain analysis of mood swings and treatment modalities of 18 bipolar II with 31 bipolar I patients.
During an observational period of a mean of 26 months we observed an increase of euthymic days, and a decrease of (sub)depressive and (hypo)manic days. Days in a (sub)depressed state were more frequent than days of (hypo)mania as well as days of subdepression or hypomania in comparison to days of full-blown depression or mania. Bipolar II patients showed an increase in hypomanic days receiving more frequently antidepressants. Bipolar I patients, with a decrease of manic days, were significantly taking more often mood stabilizers.
Treatment in a specialized bipolar clinic improves the overall outcome, but bipolar II disorder seems to be still treated sub-optimally with a possible iatrogenic increase of hypomanic days.
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of depression has been assigned to the noradrenalin and serotonin system. Results of different studies also support a role of the dopaminergic system in depression: In particular, psychomotor retarded depressive patients exhibited lower levels of homovanillic acid (metabolite of dopamine). While the moodimproving effect of methylphenidat, D-amphetamine and cocaine is also supportive for an involvement of the dopaminergic system, reserpine leads to diminished dopamine levels and may induce a depressive syndrome as well as dopamine receptor-blockers. Dopamine-mediated motor disturbances and accompanying changes in mood in Parkinson's disease likewise support pathophysiological similarities of depression and Parkinson's disease. Psychomotor inhibition, reduced facial expression and decreased speech production in depression are in line with a hypodopaminergic state of the respective motor areas. There is evidence from open studies for the ergotalkaloids bromocriptine and pergolide to have anti-depressive effects. Controlled studies for the selective dopamine D2/D3-agonists pramipexole and ropinirole are existing. Bupropion, a selective dopamine and noradrenaline reuptake inhibitor (DNRI), has proven antidepressant efficacy in controlled studies and has been licensed for the treatment of depression.
Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation: Organ der Gesellschaft Österreichischer Nervenärzte und Psychiater 02/2009; 23(1):15-25. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The serotonergic system is involved in the pathophysiology of major depression as well as in the early central nervous system development and adult neuroplasticity. The aim of the study was to examine in 77 patients with major depression and 77 healthy controls the association between the triallelic polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and gray matter (GM) brain volumes measured with 1.5 T magnetic resonance imaging. Voxel-based morphometry were estimated on magnetic resonance images and genotyping was performed. We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele, indicating that 5-HTTLPR contributes to the development of brain structures. Patients with depression show reduced GM volumes, particularly when they are homozygous for the L(A)-allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes.
[Show abstract][Hide abstract] ABSTRACT: In this study the predictive value of the combined dexamethasone/CRH test (DEX/CRH test) for acute antidepressant response was investigated.
In 114 depressed inpatients suffering from unipolar or bipolar depression (sample 1) the DEX/CRH test was performed at admission and shortly before discharge. During their stay in the hospital patients received different antidepressant treatment regimens. At admission, the rate of nonsuppression (basal cortisol levels >75.3 nmol/l) was 24.6% and was not related to the later therapeutic response. Moreover, 45 out of 114 (39.5%) patients showed an enhancement of HPA axis function at discharge in spite of clinical improvement. In a second sample, 40 depressed patients were treated either with reboxetine or mirtazapine for 5 weeks. The DEX/CRH test was performed before, after 1 week, and after 5 weeks of pharmacotherapy. Attenuation of HPA axis activity after 1 week was associated with a more pronounced alleviation of depressive symptoms after 5-week mirtazapine treatment, whereas downregulation of HPA system activity after 5 weeks was related to clinical response to reboxetine. However, early improvement of HPA axis dysregulation was not necessarily followed by a beneficial treatment outcome.
Taken together, performance of a single DEX/CRH test does not predict the therapeutic response. The best predictor for response seems to be an early attenuation of HPA axis activity within 1 or 2 weeks. However, early improvement of HPA system dysfunction is not a sufficient condition for a favourable response. Since a substantial part of depressive patients display a persistence of HPA axis hyperactivity at discharge, downregulation of HPA system function is not a necessary condition for acute clinical improvement either. Our data underline the importance of HPA axis dysregulation for treatment outcome in major depression, although restoration of HPA system dysfunction seems to be neither a necessary nor a sufficient determinant for acute treatment response.
PLoS ONE 01/2009; 4(1):e4324. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid-cycling bipolar disorder is often characterized by a lack of response to psychopharmacological treatment, and a standard therapy has not been developed yet. The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid-cycling bipolar disorder.
This open-label, randomized, parallel group monotherapy pilot study was conducted at 3 German centers. A sample of 38 remitted or partly remitted patients with bipolar disorder and rapid cycling (quetiapine n = 22; VPA n = 16) were treated with quetiapine or VPA (flexible dose design) for 12 months.
Forty-one percent of the patients with quetiapine and 50% with VPA completed the trial. On the basis of ITT-LOCF, Life Chart Method data showed that patients being treated with quetiapine had significantly less moderate to severe depressive days than patients on VPA (mean +/- SD, 11.7 +/- 16.9 days vs 27.7 +/- 24.9 days; P = 0.04) while they did not differ in the number of days with manic or hypomanic symptoms. Furthermore, according to the Clinical Global Impression Scale, bipolar version, the responder rates tended to be higher for quetiapine than for VPA. There were no differences found evaluating the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Scale, and the Young Mania Rating Scale. The incidence of adverse events, especially of orthostatic dysregulation, sedation, and weight gain, was significantly higher in the quetiapine group.
In this study, quetiapine was more effective than VPA on the number of depressive days and similar to VPA in the treatment of manic symptoms. Quetiapine was associated with a greater incidence of side effects, particularly orthostatic dysregulation, sedation, and weight gain.
Journal of clinical psychopharmacology 11/2008; 28(5):555-60. · 5.09 Impact Factor