Publications (21)129.83 Total impact
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Article: Mirtazapine Provokes Periodic Leg Movements during Sleep in Young Healthy Men.
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ABSTRACT: Recent evidence suggests that certain antidepressants are associated with an increase of periodic leg movements (PLMS) that may disturb sleep. So far, this has been shown in patients clinically treated for depression and in cross-sectional studies for various substances, but not mirtazapine. It is unclear whether antidepressants induce the new onset of PLMS or only increase preexisting PLMS, and whether this is a general property of the antidepressant or only seen in depressed patients. We report here the effect of mirtazapine on PLMS in young healthy men. Open-labeled clinical trial (NCT00878540) including a 3-week preparatory phase with standardized food, physical activity, and sleep-wake behavior, and a 10-day experimental inpatient phase with an adaptation day, 2 baseline days, and 7 days with mirtazapine. Research institute. Twelve healthy young (20-25 years) men. Seven days of nightly intake (22:00) of 30 mg mirtazapine. Sleep was recorded on 2 drug-free baseline nights, the first 2 drug nights, and the last 2 drug nights. Eight of the 12 subjects showed increased PLMS after the first dose of mirtazapine. Frequency of PLMS was highest on the first drug night and attenuated over the course of the next 6 days. Three subjects reported transient restless legs symptoms. Mirtazapine provoked PLMS in 67% of young healthy males. The effect was most pronounced in the first days. The possible role of serotonergic, noradrenergic and histaminergic mechanisms in mirtazapine-induced PLMS is discussed. CITATION: Fulda S; Kloiber S; Dose T; Lucae S. Mirtazapine provokes periodic leg movements during sleep in young healthy men. SLEEP 2013;36(5):661-669.Sleep 01/2013; 36(5):661-9. · 5.05 Impact Factor -
Article: Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels.
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ABSTRACT: Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9×10(-5)) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR(⁎)D) studies, nominal associations of several polymorphisms in the upstream vicinity of rs10487506 with treatment outcome were detected (p=0.001). In addition, we determined leptin mRNA expression in lymphocytes and leptin serum levels in subsamples of the MARS study. Unfavorable treatment outcome was accompanied with decreased leptin mRNA and leptin serum levels. Our results suggest an involvement of leptin in antidepressant action and cognitive function in depression with genetic polymorphisms in the leptin gene, decreased leptin gene expression and leptin deficiency in serum being risk factors for resistance to antidepressant therapy in depressed patients.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 09/2012; · 3.68 Impact Factor -
Article: ANK3 and CACNA1C--missing genetic link for bipolar disorder and major depressive disorder in two German case-control samples.
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ABSTRACT: Recent genome-wide association studies (GWAS) and metaanalyses revealed genetic associations for ANK3 (ankyrin 3) and CACNA1C (alpha 1C subunit of the L-type voltage gated calcium channel) with bipolar disorder (BPD). Several findings from clinical, epidemiological, and genetic studies point towards a common biological background of BPD and major depressive disorder (MDD). We were interested whether this also applies for ANK3 and CACNA1C and tested associations of single nucleotide polymorphisms (SNPs) in these genes with MDD in two Caucasian case-control samples. Sample 1 (Munich Antidepressant Response Signature Project/MARS - MDD) consisted of 720 depressed inpatients and 542 psychiatric healthy controls. Sample 2 (unipolar recurrent depression (URD)) consisted of 827 patients with URD and 860 psychiatric healthy controls. After stringent quality control we analyzed 262 SNPs (sample 1) and 504 SNPs (sample 2) and imputed further 5771 SNPs (sample 1) and 5534 SNPs (sample 2) from Hapmap Phase 2 data in the ANK3 and CACNA1C gene regions. Additionally, a metaanalysis of both samples was performed. Several SNPs in both genes were nominally associated with MDD with the highest association in the 3'-region of ANK3 (rs10994143, nominal p = 3.3*10(-4)) in the metaanalysis of both samples. None of these results remained significant after correction for multiple testing. No association of MDD with SNPs previously reported in BPD studies could be detected. By analyzing the LD-structure, our highest associated SNPs could not be linked to the SNPs previously reported in BPD. Regarding ANK3 and CACNA1C, our findings do not support a strong genetic link between BPD and MDD for these two genes.Journal of psychiatric research 05/2012; 46(8):973-9. · 3.72 Impact Factor -
Article: Polymorphisms within the metabotropic glutamate receptor 1 gene are associated with depression phenotypes.
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ABSTRACT: Glutamate has been implicated in the pathophysiology and treatment of mood disorders possibly by affecting the regulation of the hypothalamus-pituitary-adrenocortical (HPA) axis. Growing evidence suggests an important role of the metabotropic glutamate receptor 1 (mGlu1) in depression-related phenotypes. To test whether these findings can also be supported by human genetics data, we explored polymorphisms within the metabotropic glutamate receptor 1 gene (GRM1) for their association with unipolar depression (UPD) as well as with biological phenotypes of this disorder. We first tested the association of 43 tag-SNPs covering the GRM1 locus with UPD in 350 patients and 370 matched controls. We then investigated the effects of the associated SNPs on hippocampal glutamate levels estimated using ¹H-MR-spectroscopy (¹H-MRS) and on endocrine measures from the combined dexamethasone-suppression/CRH stimulation (dex/CRH) test. Within the GRM1 locus, 22 SNPs showed nominally significant association with UPD, of which 6 withstood corrections for multiple testing (rs2268666 with best allelic p=7.0×10⁻⁵). Supportive evidence for an association with UPD was gained from a second independent sample with 904 patients and 1012 controls. Furthermore, patients homozygous for the non-risk genotypes showed reduced hippocampal glutamate levels as measured by ¹H-MRS, a more pronounced normalization of HPA-axis hyperactivity as well as a better antidepressant treatment outcome. These results suggest that the combination of genetic and biological markers may allow to subgroup patients into etiopathogenetically more relevant subcategories which could guide clinicians in their antidepressant treatment choices.Psychoneuroendocrinology 09/2011; 37(4):565-75. · 5.81 Impact Factor -
Article: Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients.
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ABSTRACT: A consistent body of evidence supports a role of reduced neurotrophic signaling in the pathophysiology of major depressive disorder (MDD) and suicidal behavior. Especially in suicide victims, lower postmortem brain messenger RNA and protein levels of neurotrophins and their receptors have been reported. To determine whether the brain-derived neurotrophic factor (BDNF) gene or its high-affinity receptor gene, receptor tyrosine kinase 2 (NTRK2), confer risk for suicide attempt (SA) and MDD by investigating common genetic variants in these loci. Eighty-three tagging single-nucleotide polymorphisms (SNPs) covering the genetic variability of these loci in European populations were assessed in a case-control association design. Inpatients and screened control subjects. The discovery sample consisted of 394 depressed patients, of whom 113 had SA, and 366 matched healthy control subjects. The replication studies comprised 744 German patients with MDD and 921 African American nonpsychiatric clinic patients, of whom 152 and 119 were positive for SA, respectively. Blood or saliva samples were collected from each participant for DNA extraction and genotyping. Associations of SNPs in BDNF and NTRK2 with SA and MDD. Independent SNPs within NTRK2 were associated with SA among depressed patients of the discovery sample that could be confirmed in both the German and African American replication samples. Multilocus interaction analysis revealed that single SNP associations within this locus contribute to the risk of SA in a multiplicative and interactive fashion (P = 4.7 x 10(-7) for a 3-SNP model in the combined German sample). The effect size was 4.5 (95% confidence interval, 2.1-9.8) when patients carrying risk genotypes in all 3 markers were compared with those without any of the 3 risk genotypes. Our results suggest that a combination of several independent risk alleles within the NTRK2 locus is associated with SA in depressed patients, further supporting a role of neurotrophins in the pathophysiology of suicide.Archives of general psychiatry 04/2010; 67(4):348-59. · 12.26 Impact Factor -
Article: Gender-specific association of galanin polymorphisms with HPA-axis dysregulation, symptom severity, and antidepressant treatment response.
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ABSTRACT: Galanin (GAL) is an estrogen-inducible neuropeptide, highly expressed in brain regions reported to be involved in regulation of mood and anxiety. GAL possibly has a direct modulatory effect on hypothalamic-pituitary-adrenal (HPA)-axis regulation. Recent data from pharmacological and genetic studies indicate a significant function of GAL in stress-related disorders. By using a tag SNP approach covering the locus encoding preprogalanin (PPGAL), earlier findings of female-specific associations of polymorphisms in this locus with panic disorder were expanded to a larger sample of 268 outpatients with anxiety disorders (ADs). Within a larger sample of 541 inpatients with major depressive disorder (MDD), we then tested associations of one PPGAL tag SNP with specific depression symptom clusters and HPA-axis activity assessed by the combined dexamethasone-suppression/CRH-stimulation test both at inpatient admission and discharge (n=298). Gender specificity as well as dependence of the association on levels of circulating estrogens was analyzed. Genotyping revealed high linkage disequilibrium in the promoter area of the PPGAL gene, which includes several estrogen-response elements. Confirming earlier results, rs948854, tagging this promoter region, was associated with more severe anxiety pathology in female AD patients, but not in males. In premenopausal female MDD patients, the same allele of rs948854 was associated with more severe vegetative but not cognitive depressive symptoms at discharge and worse treatment response on antidepressant medication. Furthermore, this allele was associated with higher HPA-axis activity at admission. No significant case-control associations could be observed. However, because of power limitations of both patient samples, small effects cannot be excluded. The reported associations in independent samples of AD and MDD support an estrogen-dependent function of GAL in pathophysiology of anxiety and depression, affecting response to antidepressant treatment.Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2010; 35(7):1583-92. · 6.99 Impact Factor -
Article: A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression.
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ABSTRACT: The efficacy of antidepressant drug treatment in depression is unsatisfactory; 1 in 3 patients does not fully recover even after several treatment trials. Genetic factors and clinical characteristics contribute to the failure of a favorable treatment outcome. To identify genetic and clinical determinants of antidepressant drug treatment outcome in depression. Genomewide pharmacogenetic association study with 2 independent replication samples. We performed a genomewide association study in patients from the Munich Antidepressant Response Signature (MARS) project and in pooled DNA from an independent German replication sample. A set of 328 single-nucleotide polymorphisms highly related to outcome in both genomewide association studies was genotyped in a sample of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. A total of 339 inpatients with a depressive episode (MARS sample), a further 361 inpatients with depression (German replication sample), and 832 outpatients with major depression (STAR*D sample). We generated a multilocus genetic variable that described the individual number of alleles of the selected single nucleotide polymorphisms associated with beneficial treatment outcome in the MARS sample ("response" alleles) to evaluate additive genetic effects on antidepressant drug treatment outcome. Multilocus analysis revealed a significant contribution of a binary variable that categorized patients as carriers of a high vs low number of response alleles in the prediction of antidepressant drug treatment outcome in both samples (MARS and STAR*D). In addition, we observed that patients with a comorbid anxiety disorder combined with a low number of response alleles showed the least favorable outcome. These results demonstrate the importance of multiple genetic factors combined with clinical features in the prediction of antidepressant drug treatment outcome, which underscores the multifactorial nature of this trait.Archives of general psychiatry 10/2009; 66(9):966-75. · 12.26 Impact Factor -
Article: Selected summaries from the XVI World Congress of Psychiatric Genetics, Osaka, Japan, 11-15 October 2008.
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ABSTRACT: The XVI World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics took place in Osaka, Japan, October 2008. Approximately 600 participants gathered to discuss the latest molecular genetic findings relevant to serious mental illnesses, including schizophrenia, bipolar disorder, major depression, alcohol and drug abuse, autism, and attention-deficit disorder. Recently, the field has advanced considerably and includes new genome-wide association studies with the largest numbers of individuals screened and density of markers to date, as well as newly uncovered genetic phenomena, such as copy number variation that may prove to be relevant for specific brain disorders. The following report represents some of the areas covered during this conference and some of the major new findings presented.Psychiatric genetics 09/2009; 19(5):219-36. · 2.33 Impact Factor -
Article: Polymorphisms in the GAD2 gene-region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders.
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ABSTRACT: Glutamate decarboxylase (GAD) is the rate limiting enzyme for conversion of glutamic acid to gamma-aminobutyric acid (GABA). The GAD 65 kDa isoform is encoded by the gene GAD2 and is mainly expressed in synaptic terminals. It serves as an apoenzyme, which shows enhanced availability in situations of stress, responding to short-term demands for GABA. We analyzed 18 single nucleotide polymorphisms (SNPs) in the GAD2-gene region for associations with psychiatric diagnosis and behavioral inhibition (BI) derived from the personality traits neuroticism and extraversion as defined by the Eysenck Personality Questionaire (EPQ). A total of 268 patients with anxiety disorder (AD), 541 with unipolar depression (MD), and 541 healthy controls were included. We observe associations for five tag-SNPs with BI in the AD- and control samples as well as two additional case-control associations in the MD-sample. The associated SNPs lie within a 16KB linkage disequilibrium-block, including putative 5' GAD2-promoter-elements as well as the 3' end of the gene MYO3A. Using open access mRNA-expression data, we could show that BI-associated SNPs appear to be associated with differences in MYO3A- but not GAD2 lymphoblastoid-mRNA expression levels. These results support earlier studies that suggest associations of polymorphisms within the GAD2 locus with anxiety and affective disorders. However, data from expression studies imply that these polymorphisms could tag functional effects on the neighboring gene MYO3A, which is also expressed in the brain, including the cingulate cortex and the amygdala.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2009; 150B(8):1100-9. · 3.70 Impact Factor -
Article: Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls.
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ABSTRACT: Mood and anxiety disorders are considered stress-related diseases characterized by an impaired function of mineralocorticoid and glucocorticoid receptors (MR and GR, respectively), the major regulatory elements of the hypothalamus-pituitary-adrenocortical (HPA) axis. A number of so-called chaperone proteins moderate the function of these receptors. Genetic variations in one of these chaperones, FKBP5, were associated with antidepressant treatment response in depression and with a major risk-factor for the development of posttraumatic stress disorder. To further investigate the effect of FKPB5 polymorphisms on corticosteroid receptor-mediated HPA axis regulation we conducted the Trier Social Stress test, a standardized procedure to evaluate psychosocial stress response, in 64 healthy volunteers. We genotyped rs4713916, rs1360780 and rs3800737, the three single nucleotide polymorphisms (SNPs) in the FKBP5 region which had shown the strongest effect in previous studies. In addition, we evaluated the effects of the GR polymorphisms Bcl1 and N363S as well as the MR polymorphism I180V. Subjects homozygous for any of the FKBP5 variants displayed an incomplete normalization of the stress-elicited cortisol secretion. This was also observed following a second test additionally accompanied by an increased self-reported anxiety. Regarding GR and MR, only carriers of the Bcl1 variant displayed an altered cortisol response in the prognosticated direction. While Bcl1 was predominantly associated with anticipatory cortisol, homozygous carriers of the FKBP5 minor allele showed insufficient cortisol recovery and increased self-reported anxiety after psychosocial stress. This reaction pattern suggests that subjects carrying these variants are at risk of displaying chronically elevated cortisol levels after repeated stress constituting a risk factor for stress-related diseases.European Journal of Neuroscience 08/2008; 28(2):389-98. · 3.63 Impact Factor -
Article: Genetic markers within glutamate receptors associated with antidepressant treatment-emergent suicidal ideation.
American Journal of Psychiatry 08/2008; 165(7):917-8. · 12.54 Impact Factor -
Article: Clinical characteristics and treatment outcome in a representative sample of depressed inpatients - findings from the Munich Antidepressant Response Signature (MARS) project.
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ABSTRACT: Depression is a common and often difficult-to-treat clinical condition with a high rate of patients showing insufficient treatment response and persistence of symptoms. We report the characteristics of a representative sample of depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Eight hundred and forty-two inpatients admitted to a psychiatric hospital for treatment of a major depressive episode, recurrent or bipolar depression were thoroughly characterized with respect to demographic factors, clinical history, and the degree of HPA-axis dysregulation evaluated by means of combined dex/CRH tests, and the predictive value of these factors for treatment outcome is investigated. 80.8% of patients responded to treatment (i.e., improvement in symptom severity of at least 50%) and 57.9% reached remission (i.e., near absence of residual depressive symptoms) at discharge after a mean treatment period of 11.8 weeks. Regression analysis identified early partial response (within 2 weeks) as the most important positive predictor for achieving remission. Previous ineffective treatment trials in the current episode and presence of a migration background are potent negative predictors for treatment outcome. In addition, remitters were characterized by a more pronounced normalization of an initially dysregulated HPA-axis. We could show that a large majority of inpatients suffering from depression benefits from antidepressant treatment during hospitalization. However, a considerable number of patients failed to achieve remission. We demonstrated that this subgroup can be characterized by a set of demographic, clinical and neuroendocrine variables allowing to predict unfavorable outcome at an early stage of treatment.Journal of Psychiatric Research 07/2008; 43(3):215-29. · 4.66 Impact Factor -
Article: Polymorphisms in the angiotensin-converting enzyme gene region predict coping styles in healthy adults and depressed patients.
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ABSTRACT: Dispositional coping styles are important moderators of the stress reaction and are altered in stress-related disorders like cardiovascular diseases and affective disorders. Heritability studies suggest a considerable genetic contribution to the interindividual variability in coping styles. Since the angiotensin-converting enzyme (ACE) gene has been described to be associated with the vulnerability for stress-related disorders and with altered stress hormone regulation, we investigated the ACE gene as potential candidate gene for coping styles. Five hundred forty one mentally healthy subjects and 194 patients suffering from depression participating in the Munich Antidepressant Response Signature (MARS) project were examined. Coping styles were assessed with a self-report questionnaire (German Stress Coping Questionnaire SVF78) measuring the individual coping style pattern in response to stressful situations. We genotyped 15 single nucleotide polymorphisms (SNPs) and the insertion/Deletion (I/D)-polymorphism in the ACE gene region and investigated their associations with coping styles. In healthy subjects, the highest association was observed between rs8066276, an intronic SNP of the ACE gene, and the coping factor Distraction. A further intronic SNP rs4305, not in linkage disequilibrium with rs8066276, showed an association with Devaluation/Defense. All associated copying styles can be categorized as potentially stress reducing factors (positive coping). Both SNPs were also found to be associated with positive coping styles in the patient sample; rs8066276 was associated with Devaluation/Defense, and rs4305 showed associations with Control. These results suggest that the ACE gene is involved in the development of coping strategies.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 06/2008; 150B(1):104-14. · 3.70 Impact Factor -
Article: Polymorphisms in the galanin gene are associated with symptom-severity in female patients suffering from panic disorder.
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ABSTRACT: Galanin (GAL) is a neuropeptide, which is expressed primarily in limbic nuclei in the brain and mediates miscellaneous physiological processes and behaviors. In animal studies, both the application of GAL and antagonism of its receptors have been shown to affect anxiety-like and depression-related behavior. In humans, intravenous administration of the neuropeptide galanin has been reported to have fast antidepressant efficacy. Furthermore, GAL is involved in hypothalamic-hypophysiotropic signalling and cosecreted with luteinizing hormone-releasing hormone (LHRH), possibly acting as a mediator of estrogen action. In this study six single nucleotide polymorphisms (SNPs) within the gene coding for GAL were analyzed for possible associations with diagnosis and severity of symptoms in 121 male and female patients suffering from panic disorder (PD). Our results suggest an association between genetic variations in the GAL-gene and severity of PD-symptoms in female patients. The most pronounced effects could be observed for two haplotypes containing the closely linked, non-protein-coding SNPs rs948854 and rs4432027. Both polymorphisms are located within CpG-dinucleotides in the promoter region of GAL and thus might be involved in epigenetic regulation of the GAL-gene. A relatively small patient sample was analyzed in this study, the herein presented results need to be validated in independent studies. The results of this study underline the potential of further genetic research concerning GAL and a possible role of this neuropeptide in the pathogenesis of female PD. In this regard, GAL and its receptors appear to be a promising target for pharmacological therapy of anxiety and affective disorders.Journal of Affective Disorders 02/2008; 105(1-3):177-84. · 3.52 Impact Factor -
Article: Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression.
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ABSTRACT: The clinical efficacy of a systemically administered drug acting on the central nervous system depends on its ability to pass the blood-brain barrier, which is regulated by transporter molecules such as ABCB1 (MDR1). Here we report that polymorphisms in the ABCB1 gene predict the response to antidepressant treatment in those depressed patients receiving drugs that have been identified as substrates of ABCB1 using abcb1ab double-knockout mice. Our results indicate that the combined consideration of both the medication's capacity to act as an ABCB1-transporter substrate and the patient's ABCB1 genotype are strong predictors for achieving a remission. This finding can be viewed as a further step into personalized antidepressant treatment.Neuron 02/2008; 57(2):203-9. · 14.74 Impact Factor -
Article: Persistent cognitive impairment in depression: the role of psychopathology and altered hypothalamic-pituitary-adrenocortical (HPA) system regulation.
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ABSTRACT: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system and cognitive impairment are consistent findings in depression. This study examines the associations between HPA system regulation, cognitive functioning, and psychopathology in depressed inpatients on admission and at discharge. The HPA system dysregulation was evaluated with the dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test. Cognitive assessment included speed of information processing, divided and selective attention, as well as short-term and working memory. Psychopathology was evaluated with the Hamilton Rating Scale for Depression (HAMD). Data from 75 depressed inpatients are reported, 51 (68%) of them achieved remission. Despite a significant reduction of depressive symptoms between admission and discharge, a high rate of patients remained cognitively impaired. Selective attention improved significantly in remitters and nonremitters, while speed of information processing increased only in remitters. The cortisol response to the DEX/CRH test decreased significantly only in remitters, which was uncorrelated with cognitive performance. In nonremitters, severity of depression was significantly correlated with information processing time while improvement in short-term memory was negatively associated with the cortisol response at discharge. Our data support the assumption that psychopathological symptoms and the HPA system dysregulation can be dissociated in their impact on cognitive functioning in depressed patients.Biological Psychiatry 10/2007; 62(5):400-6. · 8.28 Impact Factor -
Article: Overweight and obesity affect treatment response in major depression.
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ABSTRACT: Epidemiologic and clinical studies suggest comorbidity between major depressive disorder (MDD) and obesity. To elucidate the impact of weight on the course of depression beyond comorbidity, we investigated psychopathology, attention, neuroendocrinology, weight change, and treatment response in MDD patients, depending on their weight. Four hundred eight inpatients with MDD participated in the Munich Antidepressant Response Signature Study, designed to discover biomarkers and genotypes that are predictive for clinical outcome. Psychopathology and anthropometric parameters were monitored weekly in 230 patients. In subsamples, combined dexamethasone-corticotropin-releasing hormone and attention tests were conducted at admission and discharge. One thousand twenty-nine diagnosed matched controls served for morphometric comparisons. Patients with MDD had a significantly higher body mass index (BMI) compared with healthy controls. Patients with high BMI (> or =25) showed a significantly slower clinical response, less improvement in neuroendocrinology and attention, and less weight gain than did patients with normal BMI (18.5 < or = BMI < 25) during antidepressant treatment. Our findings suggest that overweight and obesity characterize a subgroup of MDD patients with unfavorable treatment outcome.Biological Psychiatry 08/2007; 62(4):321-6. · 8.28 Impact Factor -
Article: Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression - a potential biomarker?
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ABSTRACT: Exaggerated corticotropin (ACTH) and cortisol response to the combined dexamethasone (DEX)/corticotropin releasing hormone (CRH) test, indicating impaired regulation of the hypothalamus-pituitary-adrenocortical (HPA) system, is frequently observed in depression. In the present study, we examined whether change in HPA system function during the first weeks of hospitalization predicts response to antidepressant treatment in major depression and thus constitutes a potential biomarker. We conducted the DEX/CRH test in 50 inpatients suffering from severe major depression, once after study inclusion and a second time 2 to 3 weeks later while under continuous antidepressant treatment. We found increased ACTH and cortisol responses to the first DEX/CRH test compared with healthy control subjects. In the second DEX/CRH test 2 to 3 weeks later, 36 of the 50 patients showed an attenuated cortisol response, while 14 patients did not display improvement or exhibited even aggravation of the altered HPA system function. Improved HPA system regulation in the second DEX/CRH test was associated with beneficial treatment response after 5 weeks and a higher remission rate at the end of hospitalization. The results suggest that change in HPA system regulation assessed with repeated DEX/CRH tests is a potential biomarker that may predict clinical outcome at follow-up. There is consensus that the drug development process could be improved, once reliable biomarkers become available that help to allow a judgement regarding the efficacy of a novel drug candidate. The combined DEX/CRH test seems to be a promising candidate for such a biomarker.Biological Psychiatry 08/2007; 62(1):47-54. · 8.28 Impact Factor -
Article: Polymorphisms in the serotonin receptor gene HTR2A are associated with quantitative traits in panic disorder.
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ABSTRACT: Anxiety disorders and specifically panic disorder (PD) are caused by complex interactions of environmental and genetic factors. The latter comprise many different genes, from which those involved in serotonergic neurotransmission have received particular attention. Here we report the results from an association candidate-gene approach, where we analyzed 15 single nucleotide polymorphisms (SNPs) within the gene coding for the serotonin-receptor 2A (HTR2A) in patients suffering from PD and a control sample. We found that the SNP rs2296972 shows an association between the number of T-alleles and severity of symptoms in PD. By performing tests according to the Fisher product method (FPM), an association between HTR2A and the personality trait reward dependence could be shown. Most pronounced effects were observable for the SNPs rs2770304, rs6313, and rs6311. Furthermore, the polymorphisms rs3742278, rs2296972, and rs2770292 form a haplotype, which may be associated with higher susceptibility for PD. These results further underline a possible important role of genetic variations within the system controlling serotonergic neurotransmission for the development and course of disease in PD.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 07/2007; 144B(4):424-9. · 3.70 Impact Factor -
Article: Changes in the hypothalamic-pituitary-adrenal axis and leptin levels during antidepressant treatment.
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ABSTRACT: In depressed patients, overstimulation of the hypothalamo-pituitary-adrenocortical (HPA) system, probably caused by glucocorticoid receptor resistance, is the most consistent neurobiological finding. Glucocorticoids themselves are reported to increase leptin synthesis and secretion in humans. We examined alterations in plasma levels of leptin as well as changes in the HPA system function using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 74 depressed inpatients. Mean leptin concentration did not change significantly between admission and discharge. However, changes in ACTH response and partial cortisol response to the combined dex/CRH test between admission and discharge were significantly correlated with leptin levels at discharge. Leptin levels at discharge rise as the HPA axis normalizes. These findings may be explained by an improvement in glucocorticoid receptor sensitivity among depressed patients during antidepressant therapy and a consecutively increased influence of glucocorticoids on leptin levels via the glucocorticoid receptor.Neuropsychobiology 02/2007; 55(1):28-35. · 2.67 Impact Factor
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2007–2012
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Max-Planck-Institut für Psychiatrie
München, Bavaria, Germany
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