Biomedical subjects

Hans-Jürgen Möller

Publications and source records attributed to Hans-Jürgen Möller.

At least 19 recordsLinked to original sources

PubMed2007

HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers.

The serotonin 2C (HTR2C) and 1A (HTR1A) receptors have been involved in suicide-related behaviors. We studied gene variants of both receptors in suicide attempters and completers. The sample was composed of 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide, 312 German healthy subjects, 152 Italian suicide attempters (major depression n = 68 and bipolar disorder n = 84), and 131 Italian healthy volunteers. HTR2C (SNP: rs547536, rs2192372, rs6318, rs2428707, rs4272555, rs1801412) and HTR1A (SNP: rs1423691, rs878567, and rs6295) variants were analyzed in the German sample. HTR2C rs6318 and HTR1A rs6295 were analyzed in the Italian sample. Haplotype analysis in relation to suicidal behaviors did not reveal any significant association. Single markers and haplotypes were not or only marginally associated with other related features, such as violence of suicide attempt, family history for suicide attempt or State-Trait Anger Expression Inventory (STAXI) and Questionnaire for Measuring Factors of Aggression (FAF) scores. In conclusion, our study does not support the notion that HTR2C and HTR1A gene variants are major contributors to suicide-, anger-, or aggression-related behaviors in our sample.

Adolescent↗

PubMed2007

Depressive, anxiety, and somatoform disorders in primary care: prevalence and recognition.

Recent studies emphasize the negative impact of comorbidity on the course of depression. If undiagnosed, depression and comorbidity contribute to high medical utilization. We aimed to assess (1) prevalences of depression alone and with comorbidity (anxiety/somatoform disorders) in primary care, (2) coexistence of anxiety/somatoform disorders in depressive patients, and (3) diagnostic validity of two screeners regarding depression with versus without comorbidity. We examined 394 primary care outpatients using the Composite International Diagnostic Interview (CIDI), the General Health Questionnaire (GHQ-12), and the Well-Being Index (WHO-5). We conducted configurational frequency analyses to identify nonrandom configurations of the disorders and receiver operating characteristic (ROC)-analyses to assess diagnostic validity of the screeners. Point prevalence of any depressive disorder was 22.8%; with at least one comorbid disorder, 15%; and with two comorbid conditions, 6.1%, which significantly exceeded expected percentage (0.9%, P< or =.0001). Depression without comorbidity occurred significantly less often than expected by chance (P< or =.0007). Comorbidity of depressive and anxiety or somatoform disorders was associated with a high odds ratio (6.25). The screeners were comparable regarding their diagnostic validity for depression with [GHQ-12: area under the curve (AUC)=0.86; WHO-5: AUC=0.88] and without comorbidity (GHQ-12: AUC=0.84; WHO-5: AUC=0.86). It can be concluded that comorbidity between depression and anxiety/somatoform disorders in primary care may occur much more frequently than expected. These results confirm assumptions that the current division between depression and anxiety might be debatable. Validity of screeners tested in our study was not affected by comorbid conditions (e.g., anxiety or somatoform disorders).

Adolescent↗

PubMed2007

Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders.

OBJECTIVE: The aim was to investigate the hypothesis that patients with first episode schizophrenic disorders have a more favorable treatment response than those with multiple episodes. METHOD: A total of 400 inpatients from an ongoing multi-centre, follow-up program who fulfilled ICD-10 criteria for schizophrenic disorders (F2) were assessed at admission to and discharge from hospital using the Positive and Negative Syndrome Scale (PANSS). RESULTS: At admission, first episode patients (n = 121) showed higher levels of positive symptoms (PANSS positive subscore) and lower ones of negative symptoms (PANSS negative subscore) than multiple episode patients (n = 279), whereas the global disease severity (PANSS total score) was comparable. Analyses of covariance revealed that treatment response (adjusted symptom levels at discharge) was more favorable in first-episode patients, with respect to both positive and negative symptoms. CONCLUSION: The results are compatible with the hypothesis that treatment response becomes less favorable during the course of schizophrenic illness. This finding might be associated with progressive neurobiological alterations.

Adult↗

PubMed2007

Molecular genetic findings in suicidal behavior: what is beyond the serotonergic system?

Various studies provide consistent evidence for a genetic component in suicidal behavior. First molecular genetic studies concentrated on genes of the serotonergic system based on the biochemical evidence that serotonergic neurotransmission is implicated in this behavior. Furthermore, genes of the dopaminergic and noradrenergic neurotransmitter systems have also been the subjects of investigations in this context. Some epidemical and clinical studies showed that low serum cholesterol levels are associated with suicidal behavior and genes involved in these pathways have been investigated. Microarray experiments provide the possibility of genome-wide gene expression analysis and help to investigate associated molecular mechanisms. The aim of this article is to review molecular genetic studies in suicidal behavior and to emphasize findings on new genes.

Cholesterol↗

PubMed2006

ABCG1 gene variants in suicidal behavior and aggression-related traits.

The ABCG1 transporter seems to be involved in human cholesterol and sterol homeostasis. As alterations in cholesterol homeostasis have been widely linked to aggression, violence and suicidal behavior, we considered ABCG1 as a candidate gene for these traits. We studied 5 gene variants of ABCG1 in a sample of 571 suicide attempters, healthy controls and suicide completers. We also analyzed the relation to aggression-related traits, assessed by STAXI and FAF. Regarding the genotypes, there was no association with completed or attempted suicide with the tested SNPs. Regarding alleles, only one SNP (rs1044317) showed a slight association with suicide attempters in comparison to the controls. Interestingly, rs225374 G allele carriers had higher scores on the STAXI subscales "State Anger" and "Anger Out", as well as on the FAF subscales "Spontaneous Aggression", "Irritability" and "Aggression". Carriers of the rs914189 G allele scored higher on the FAF subscales "Spontaneous Aggression", "Reactive Aggression" and "Aggression". Carriers of the rs1044317 G allele had lower scores for STAXI "Trait Anger" and "Trait Temperament", and higher scores for STAXI "Anger Control". Our results provide evidence that the ABCG1 may influence aggression-related traits. Given that these represent intermediate phenotypes of suicidal behavior, ABCG1 might also act on suicidal behavior through these traits. The observed associations warrant further replications.

ATP Binding Cassette Transporter, Subfamily G, Mem↗

PubMed2006

Multivariate network analysis of fiber tract integrity in Alzheimer's disease.

Axonal and dendritic integrity is affected early in Alzheimer's disease (AD). Studies using region of interest or voxel-based analysis of diffusion tensor imaging data found significant decline of fractional anisotropy, a marker of fiber tract integrity, in selected white matter areas. We applied a multivariate network analysis based on principal component analysis to fractional anisotropy maps derived from diffusion-weighted scans from 15 AD patients, and 14 elderly healthy controls. Fractional anisotropy maps were obtained from an EPI diffusion sequence using parallel imaging to reduce distortion artifacts. We used high-dimensional image warping to control for partial volume effects due to white matter atrophy in AD. We found a significant regional pattern of fiber changes (p < 0.01) indicating that the integrity of intracortical projecting fiber tracts (including corpus callosum, cingulum and fornix, and frontal, temporal and occipital lobe white matter areas) was reduced, whereas extracortical projecting fiber tracts, including the pyramidal and extrapyramidal systems and somatosensory projections, were relatively preserved in AD. Effects of a univariate analysis were almost entirely contained within the multivariate effect. Our findings illustrate the use of a multivariate approach to fractional anisotropy data that takes advantage of the highly organized structure of anisotropy maps, and is independent of multiple comparison correction and partial volume effects. In agreement with post-mortem evidence, our study demonstrates dissociation between intracortical and extracortical projecting fiber systems in AD in the living human brain.

Aged↗

PubMed2006

Fiber connections between the cerebral cortex and the corpus callosum in Alzheimer's disease: a diffusion tensor imaging and voxel-based morphometry study.

Regional cortical atrophy in Alzheimer's disease (AD) most likely reflects the loss of cortical neurons. Several diffusion tensor imaging studies reported reduced fractional anisotropy (FA) in the corpus callosum in AD. The aim of this study was to investigate the association between reduced FA in the corpus callosum and gray matter atrophy in AD. Thirteen patients with AD with a mean (+/-standard deviation) age of 68.3 years (+/-11.5) and mean Mini Mental State Examination (MMSE) score of 21.8 (+/-4.8) were recruited. There were 13 control subjects with a mean age of 66.7 years (+/-6.4) and MMSE of 29.1 (+/-0.7). We used voxel-based morphometry of gray matter maps and region of interest-based analysis of FA in the corpus callosum. FA values of the anterior corpus callosum in AD patients were significantly correlated with gray matter volume in the prefrontal cortex and left parietal lobes. FA values of the posterior corpus callosum were significantly correlated with gray matter volume in the bilateral frontal, temporal, right parietal, and occipital lobes. In control subjects, no correlations were detected. Our findings suggest that decline of FA in the corpus callosum may be related to neuronal degeneration in corresponding cortical areas.

Aged↗

PubMed2006

Is there evidence for negative effects of antidepressants on suicidality in depressive patients? A systematic review.

The role of antidepressants in suicide prevention is a major public health question given the high prevalence of both depression and depression-related suicidality. Therefore all available means should be utilised to clarify the influence of antidepressants on suicidality, especially in view of the ongoing intensive debate about possible suicidality-inducing effects of antidepressants that may outweigh their traditionally hypothesised beneficial effects. This paper gives a systematic and comprehensive review of the empirical data which might indicate that antidepressants have negative effects on suicidality. First, principal methodological issues related to this research question are discussed. Thereafter, the results of controlled trials and epidemiological and cohort studies are presented. Altogether, there seems to be only a small amount of evidence from different research approaches that antidepressants, not only serotonin reuptake inhibitors (SSRIs), might induce, aggravate or increase the risk of suicidal ideation and suicide attempts. As to suicide, there are no hints in this direction. TCAs have a higher risk of fatal outcome in overdose compared to SSRIs, which, in case of mono-intoxication, carry almost no risk of lethal consequences. The ongoing discussion about suicidality-inducing effects should not prevent physicians from prescribing SSRIs and other antidepressants to their patients if they are clinically indicated. However, they should take into account potential risks and manage them by good clinical practice.

Antidepressive Agents↗

PubMed2006

Prediction of treatment response in major depression: integration of concepts.

BACKGROUND: Two promising approaches have been introduced for the prediction of treatment response in major depression: one concept is based on the activity in the rostral anterior cingulate cortex (rACC). Subjects with higher metabolic rates respond better to sleep deprivation or antidepressive medication. Another approach is the investigation of the loudness dependence of the auditory evoked potential (LDAEP). Here, a high LDAEP is supposed to reflect low central serotonergic activity. We present the first study comparing both approaches in the same group of patients. METHODS: Patients with major depression (n=20) were investigated using both resting EEG and LDAEP before treatment with either citalopram or reboxetine. RESULTS: We found significant differences between responders and non-responders in the rACC in the theta-frequency range (6.5-8 Hz, p<0.05). In the subgroup of patients, treated with citalopram we found higher LDAEP-values in responders versus non-responders (p<0.05) and a significant correlation between pre-treatment-LDAEP and improvement in the Hamilton score after treatment (r=0.71, p<0.05). CONCLUSIONS: In combining both methods a prediction whether a patient with major depression might be at risk for non-response to a standard therapy as well as a suggestion for a pharmacological approach of choice seems to be possible.

Antidepressive Agents↗

PubMed2006

Effects of repetitive transcranial magnetic stimulation (rTMS) on panic attacks induced by cholecystokinin-tetrapeptide (CCK-4).

Low-frequency (LF) rTMS shows beneficial effects in patients with depression and anxiety disorders. To explore its anxiolytic properties we investigated the effects of rTMS on experimentally induced panic attacks. Eleven healthy subjects underwent 1 Hz rTMS or sham rTMS over the right dorsolateral prefrontal cortex in a randomized cross-over protocol. Panic induction with 50 mug CCK-4 was carried out immediately after rTMS. Response to CCK-4 was assessed using the Acute Panic Inventory and the Panic Symptom Scale and measurements of heart rate, plasma ACTH and cortisol. All subjects reported a marked panic response following CCK-4 administration after both real and sham rTMS. Moreover, injection of CCK-4 induced a marked increase in heart rate, cortisol and ACTH concentrations. However, ANOVA showed no significant differences in any of the measures between both conditions. In contrast to the effects of pretreatment with alprazolam on CCK-4-induced panic in healthy subjects LF rTMS does not affect CCK-4-induced panic and cortisol or ACTH release.

Adrenocorticotropic Hormone↗

PubMed2006

Anger- and aggression-related traits are associated with polymorphisms in the 5-HT-2A gene.

BACKGROUND: This study investigates the association of four single nucleotide polymorphisms (SNPs) in the serotonin 2A (5-HT-2A) receptor gene with anger-, aggression- and suicide-related behavior in a total of 566 subjects (203 German suicide attempters and 363 German community-based healthy volunteers). METHODS: Anger- and aggression-related traits were assessed by using the State Trait Anger Expression Inventory (STAXI) and the Questionnaire for Measuring Factors of Aggression (FAF). RESULTS: Three (rs643627-rs594242-rs6311: A-C-T), two (rs594242-rs6311: C-T) and a single functional (rs6311: T) marker were protective against suicidal behavior. The complementary makers (rs594242-rs6311: G-C and rs6311: C) were associated with increased risk for non-violent (p=0.01; p=0.009 respectively) and impulsive suicidal behavior (p=0.03; p=0.01 respectively). Furthermore, CC-homozygotes for the functional SNP rs6311 reported more anger- (p=0.004) and aggression-related behavior (p=0.011). CONCLUSION: We conclude that variations in the 5-HT-2A gene may modify the phenotype of suicide-, anger-, and aggression-related behavior. Further studies should especially focus on intermediate personality traits in this context.

Adolescent↗

PubMed2006

Evidence for beneficial effects of antidepressants on suicidality in depressive patients: a systematic review.

The role of antidepressants in suicide prevention is a major public health question, given the high prevalence of both depression and depression-related suicidality. Therefore all means available should be utilised to clarify the influence of antidepressants on suicidality. This paper gives a comprehensive overview of the positive effects of antidepressants on suicidality. In the first section, principal methodological issues related to suicidology in general as well as to clinical and epidemiological studies that investigate the influence of antidepressants on suicidality are discussed. In the second section, the results of controlled clinical studies on the efficacy of antidepressants in suicidality are presented. The third section reports on the results of other types of studies, especially epidemiological studies. Altogether, there seems to be reasonable evidence from different research approaches that antidepressants are able to reduce suicidal ideation and also suicidal behaviour in depressive patients. While the evidence for the beneficial effect on suicidal ideation comes from randomised control group studies, some of which used a placebo arm, the evidence for the prophylactic effect on suicidal behaviour, especially suicide, was primarily obtained from well-designed epidemiological studies.

Antidepressive Agents↗

PubMed2006

Effects of donepezil on cortical metabolic response to activation during (18)FDG-PET in Alzheimer's disease: a double-blind cross-over trial.

RATIONALE: Cholinergic enhancement is among the best established treatments of Alzheimer's disease (AD). The cognitive effects of treatment are thought to be mediated by improvement of neuronal transmission. Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) by measuring cortical metabolic response to activation assesses integrity of neuronal transmission in vivo. OBJECTIVE: To determine the effects of treatment with donepezil, a centrally selective acetylcholinesterase inhibitor, on cortical metabolism in AD using 18FDG-PET. METHODS: We enrolled 23 patients, 18 of which completed the study, with mild to moderate probable AD (mini-mental status exam scores of 15-28, inclusive) in a double-blind cross over trial of 8 weeks donepezil compared to 8 weeks placebo with repeated double 18FDG-PET examinations during passive audio-visual stimulation. Effects of treatment on cortical metabolic response to stimulation were determined with a linear model on a voxel level using Statistical Parametric Mapping (SPM 99, Wellcome Department of Imaging Neuroscience, London). RESULTS: Effects of treatment on cognitive measures were not different between donepezil and placebo. During passive audio-visual stimulation, patients showed activation in posterior visual and auditory areas and decreased activation in frontal cortex and basal ganglia. Resting state metabolism was increased with donepezil in left prefrontal cortex and decreased in right hippocampus. Cortical response to activation was increased in right hippocampus with donepezil compared to placebo. CONCLUSION: Donepezil treatment shows a spatially limited functional effect on right hippocampus and left prefrontal cortical metabolism, independently of clinical response to treatment.

Aged↗

PubMed2006

Symptom-specific EEG power correlations in patients with obsessive-compulsive disorder.

Neurophysiological studies in patients with obsessive-compulsive disorder (OCD) consistently revealed frontal alterations of cortical activity but otherwise showed inhomogeneous results, conceivably due to variable subgroups with diverse pathomechanisms involved. The aim of this study was to investigate quantitative electroencephalography (EEG) in patients with OCD as compared to healthy controls and to correlate neurophysiological data with clinical variables. EEGs were digitally recorded from 18 unmedicated patients (8 male, mean age 32.4+/-11.8 years, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) 15.3+/-7.9) and 18 matched healthy controls, and analysed quantitatively. The mean frequency of EEG background activity and absolute power in delta, theta, alpha and beta frequency bands were calculated. Mean frequency of background activity was significantly lower in patients as compared to controls (-1.44/s, p<0.01), predominantly for the frontal electrode positions. Power spectra revealed increased delta- and decreased alpha-/beta-power in the group of patients (p<0.05, patients vs. controls). Correlation analyses showed significant positive correlations of EEG-power with the Y-BOCS sub-scores "obsessions", and negative correlations with the sub-scores "compulsions" (Spearman's correlations, r(s)=+0.48 to +0.70, and -0.47 to -0.6, respectively, p<0.05). The data provide evidence of a dysfunction of frontal cortical activity in patients with OCD. The opposite correlations of neurophysiological data and clinical features, i.e. obsessions and compulsions, are suggestive of pathophysiological differences based on the presence of the respective cardinal symptoms of OCD.

Adolescent↗

PubMed2006

Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI.

BACKGROUND: Early pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer's disease (AD). OBJECTIVE: To determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers. METHODS: We studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1-weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space. RESULTS: Volumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%. CONCLUSION: Extent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.

Aged↗

PubMed2006

Amygdala volume and depressive symptoms in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a high prevalence of comorbid psychiatric disorders, including major depression (MD). The aim of this study was to examine whether a co-occurrence of MD is associated with structural changes in the amygdala of BPD patients. METHODS: Twenty-five right-handed, female patients with BPD and 25 matched healthy control subjects were examined. Diagnoses of BPD and MD were made according to DSM IV. Depressive symptomatology was determined with the Hamilton Depression Scale (HAMD). Magnetic resonance imaging scans were performed with 1.5 T Magnetom Vision (Siemens, Erlangen, Germany). The software program "BRAINS" was applied for brain volumetry and segmentation. The amygdala was delineated as "region of interest." RESULTS: Comparison of amygdala volumes between the whole group of BPD patients and control subjects revealed no significant difference. Amygdala volumes in both hemispheres were significantly larger in BPD patients with MD compared with those without MD. There was a significant correlation in BPD patients between left amygdala volume and depressive symptoms as measured by HAMD. CONCLUSIONS: Correlation of amygdala volume with depression in BPD patients might indicate a causal relationship. Future studies should clarify whether amygdala enlargement is a risk factor for MD in BPD patients or a consequence of the affective disorder.

Adult↗

PubMed2006

Treatment of depression with atypical features: a meta-analytic approach.

The present meta-analysis addressed the empirical evidence regarding the treatment of major depression with atypical features. The superiority of monoamine oxidase inhibitors (MAOIs) compared with other antidepressants in the treatment of major depression with atypical features has been frequently reported. According to the CONSORT Statement, studies included in our meta-analysis had to meet several criteria, especially a double-blind, controlled condition and an operational diagnosis according to Diagnostic and Statistical Manual of Mental Disorders (DSM)-III or DSM-IV criteria, respectively. Four databases for research-based evidence were used in a systematic review: Medline, Embase, Psyndex and PsycInfo. Only eight publications met inclusion/exclusion criteria, resulting in 11 comparisons. Our results contrast an effect size of 0.45 (95% confidence interval) for a comparison of MAOIs vs. placebo with an effect size of 0.02 (95% confidence interval: - 0.10-0.14) for a comparison of MAOIs vs. selective serotonin reuptake inhibitors. The effect size for MAOIs vs. tricyclic antidepressants was 0.27 (95% confidence interval: 0.16-0.42). MAOIs may be more effective for atypical major depressive disorder than tricyclic antidepressants. Most clinical research has been conducted on irreversible MAOIs. Additional studies testing more recently developed antidepressants (including reversible MAOIs) with an improved safety profile would be warranted. The available data are insufficient for a direct comparison between MAOIs and selective serotonin reuptake inhibitors.

Antidepressive Agents↗

PubMed2006

Decreased T cellular immune response in schizophrenic patients.

The involvement of an alteration of the immune system in the pathogenesis of schizophrenia is discussed since many years. In particular, in vitro studies give evidence that the T helper-1 (Th1) mediated cellular immune response is deficient in schizophrenia. We therefore hypothesized that the type-IV delayed skin hypersensitivity reaction, which is effected by the Th1 immune response, is attenuated in schizophrenia patients. A prospective case-control study was performed to assess skin reactivity of 30 patients vs. 30 age and sex matched healthy controls. A standardized device with seven different antigens (Multitest Immignost) was applied intracutaneously; after 48h, the skin reactions were quantified. In general, the mean skin reaction of the schizophrenic patients were significantly smaller as compared to the healthy control group. Moreover, significantly more schizophrenic patients showed a diminished skin reaction to distinct antigens. Our findings demonstrate a markedly attenuated in vivo type-1 mediated cellular immune response in schizophrenic patients, further confirming the hypothesis of a relative Th2 shift in schizophrenia.

Adult↗