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Isabella Heuser

Publications and source records attributed to Isabella Heuser.

At least 19 recordsLinked to original sources
PubMed2011

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).

ATP-Binding Cassette Transporters↗
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↗
PubMed2006

The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication.

BACKGROUND: Recent findings in young adults suggest that rapid eye movement (REM) sleep plays a role in procedural memory consolidation. The significance of REM sleep for memory consolidation in old age has not yet been investigated. METHODS: Effects of REM sleep manipulation on declarative and procedural memory consolidation were investigated in 107 healthy older adults, ages 60-82 years. Rapid eye movement sleep deprivation was achieved by REM sleep awakenings and compared with non-REM sleep awakenings. Rapid eye movement sleep augmentation was realized physiologically by REM sleep rebound and pharmacologically by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Memory performance was tested by a paired associate list and a mirror tracing task at 9:30 pm and 7:30 am with sleep intervening between 11:00 pm and 7:00 am. RESULTS: Although REM sleep deprivation led to a significant reduction in total and phasic REM sleep, memory consolidation remained unaffected. Both REM sleep augmentation groups showed a significant increase in phasic REM sleep, whereas only pharmacological cholinergic REM sleep manipulation exerted a significant positive effect on procedural memory consolidation. CONCLUSIONS: Because only after cholinergic stimulation of phasic REM sleep procedural memory consolidation is improved, cholinergic activation seems to be a crucial component of REM sleep-related memory consolidation in old age.

Aged↗
PubMed2006

Hippocampal volume reduction and HPA-system activity in major depression.

Structural imaging studies investigating hippocampal volumes in patients suffering from major depression have yielded mixed results. Here, 24 unipolar depressed in-patients and 14 healthy controls carefully matched for age, gender, and years of education underwent quantitative magnetic resonance imaging (MRI). Saliva cortisol was measured at 0800 and 1600 h in patients during a one-week wash-out and the following 4 weeks. Hippocampal volumes were significantly reduced in the patient group even after adjusting for intracranial brain volume (ICV) and age. Across groups, age was significantly negatively correlated with uncorrected hippocampal volumes. In patients, severity of disease (baseline HAMD scores) and baseline cortisol levels were not related to hippocampal volumes. However, there was a negative association between duration of the index episode before hospitalization and hippocampal volumes. Additionally, hippocampal volumes were significantly negatively correlated with duration of illness. Finally, we observed a trend for higher hippocampal volumes in those patients who showed a subsequent decrease in cortisol levels under pharmacotherapy.

Adult↗
PubMed2006

Resistin and adiponectin in major depression: the association with free cortisol and effects of antidepressant treatment.

Major depression is associated with an increased risk for myocardial infarction. Adipokines have been shown to link obesity with metabolic disturbances. Based on this finding the present study was designed to investigate the effect of antidepressive treatment with either amitriptyline or paroxetine on circulating concentrations of resistin and adiponectin in depressed patients, and to establish, whether these adipokines are associated with the activation of the hypothalamic-pituitary-adrenal (HPA)-system. Thirty-seven depressed in-patients were treated in a double-blind, randomized protocol with either amitriptyline or paroxetine over a period of five weeks. After six drug free days blood was drawn on day 1 and again 36 days after antidepressive treatment for the measurement of resistin and adiponectin, fasting glucose and insulin concentrations. For quantification of free cortisol levels saliva was obtained daily at 0800 hours during weeks 1 and 5. While resistin concentrations decreased in patients remitting under amitriptyline and paroxetine (p<0.03), no changes were observed in non-remitters. At baseline, though not during treatment, circulating resistin concentrations correlated positively with free cortisol levels and with BMI (p<0.01). Adiponectin levels, however, did not change during treatment and were not associated with free cortisol concentrations but were instead positively related to QUICKI (p<0.03). In conclusion, the present data revealed resistin but not adiponectin to be related to free cortisol concentrations and to decline in remitters to antidepressive treatment.

Adiponectin↗
PubMed2006

Platelet 5-HT2A receptor binding and tryptophan availability in depression are not associated with recent history of suicide attempts but with personality traits characteristic for suicidal behavior.

BACKGROUND: Abnormalities in the serotonergic (5-HT) system have been implicated in the pathogenesis of suicidal behavior. Studies on peripheral serotonergic parameters as a measure for central serotonergic function in suicidal patients appear to be promising, yet failed to show a clear association with suicidality. The objective of this study was to elucidate the role of serotonergic blood parameters in depressed suicidal patients and to examine their usefulness as a potential biological marker for suicidality. A number of personality traits were assessed in order to provide a basis for a psychobiological model of suicidal behavior. METHODS: Depressed patients with a recent suicide attempt (SA; n = 59) were compared to those without history of suicide attempts (NSA; n = 28). 5-HT2A receptor binding in platelets and tryptophan/amino acid ratio in plasma were measured. Acute psychopathology and personality traits as well as characteristics of suicide attempts were assessed. RESULTS: There was no significant difference between SA and NSA in terms of peripheral serotonergic parameters as well as personality traits. However, the whole sample showed associations between certain personality traits and serotonergic platelet parameters. Furthermore, we observed a relation between suicidal ideation, lethality of suicide attempts and peripheral serotonergic markers. LIMITATIONS: The number of cases with data on peripheral markers is relatively low. The potential influence of antidepressant medication previous to study inclusion has to be taken into account. The study focussed on depressed patients only. CONCLUSIONS: Low serotonergic function is involved in the pathogenesis of suicidality, whereas the use of platelet 5-HT2A receptor activity and tryptophan availability as biological markers for suicidality in depressed patients could not be proven an appropriate tool. Alterations in the serotonergic system are associated with trait aggression and other character dimensions.

Adult↗
PubMed2006

Cerebrovascular reactivity following administration of mirtazapine in healthy probands--a randomized, placebo controlled double-blind clinical study.

INTRODUCTION: Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is important for maintaining constant cerebral blood flow. A reduced CVR increases the risk of stroke. We recently found that CVR was reduced in patients with depression. This might contribute to the higher risk of stroke that has been found in subjects suffering from depression. The characterization of pathophysiological conditions in the cerebral circulation requires the knowledge of influencing factors on CVR. We therefore investigated the influence that antidepressant administration might have on CVR in humans. METHODS: We investigated CVR in 48 healthy men before and after a 10-day application of either mirtazapine or placebo. CVR was determined by calculating the increase in cerebral blood flow velocity after stimulation with acetazolamide. Blood flow velocities were measured by transcranial Doppler ultrasound. RESULTS: There was no significant group-difference of CVR after the treatment trial compared to baseline. DISCUSSION: Mirtazapine does not seem to have an influence on CVR, or any impact on CVR might have been quickly limited by a cerebral autoregulatory response.

Adult↗
PubMed2006

Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine.

OBJECTIVE: There is substantial evidence that depression constitutes a risk factor for type 2 diabetes mellitus. A recent study has shown that high salivary cortisol levels are associated with decreased insulin sensitivity in unmedicated, depressed patients. Further, antidepressive treatment might have differential effects on hypothalamus-pituitary-adrenal (HPA) system activity. Therefore, the aim of the present study was to examine whether insulin sensitivity improves during anti-depressive treatment in depressed patients with declining HPA system activity. METHOD: Eighty inpatients with an episode of major depressive disorder (DSM-IV criteria) were treated in a double-blind, randomized protocol with either amitriptyline or paroxetine over a period of 5 weeks. After 6 drug-free days, an oral glucose tolerance test was performed on day 1 and again 35 days after antidepressive treatment. For quantification of free cortisol levels, saliva was obtained daily at 8:00 a.m. during weeks -1 (washout) and 5. The study was conducted from May 2005 to December 2005. RESULTS: The insulin sensitivity index(Matsuda) increased in only those patients who remitted from major depressive disorder as a result of treatment with either antidepressant (F = 7.0, df = 1,74; p < .01), while correcting for body mass index. Further, cortisol concentrations declined in remitters and responders to amitriptyline (F = 2.1, df = 1,70; p < .05), but not in any other subgroup. CONCLUSION: Successful antidepressive treatment with either a selective serotonin reuptake inhibitor or a tricyclic substance increases the sensitivity to insulin in nondiabetic depressed patients. The herein presented longitudinal data do not exclude the HPA system as a major contributor to insulin resistance in depressed patients, but underscore the assumption of additional factors.

Adult↗
PubMed2005

Manipulating REM sleep in older adults by selective REM sleep deprivation and physiological as well as pharmacological REM sleep augmentation methods.

Experimental approaches to manipulate REM sleep within the cognitive neuroscience of sleep are usually based on sleep deprivation paradigms and focus on younger adults. In the present study, a traditional selective REM sleep deprivation paradigm as well as two alternative manipulation paradigms targeting REM sleep augmentation were investigated in healthy older adults. The study sample consisted of 107 participants, male and female, between the ages of 60 and 82 years, who had been randomly assigned to five experimental groups. During the study night, a first group was deprived of REM sleep by selective REM sleep awakenings, while a second group was woken during stage 2 NREM sleep in matched frequency. Physiological REM sleep augmentation was realized by REM sleep rebound after selective REM sleep deprivation, pharmacological REM sleep augmentation by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Deprivation and augmentation paradigms manipulated REM sleep significantly, the former affecting more global measures such as REM sleep minutes and percentage, the latter more organizational aspects such as stage shifts to REM sleep, REM latency, REM density (only pharmacological augmentation) and phasic REM sleep duration. According to our findings, selective REM sleep deprivation seems to be an efficient method of REM sleep manipulation in healthy older adults. While physiological rebound-based and pharmacological cholinergic REM sleep augmentation methods both failed to affect global measures of REM sleep, their efficiency in manipulating organizational aspects of REM sleep extends the traditional scope of REM sleep manipulation methods within the cognitive neuroscience of sleep.

Aged↗
PubMed2005

Metabolic changes in elderly patients with major depression: evidence for increased accumulation of visceral fat at follow-up.

The accumulation of visceral fat is promoted by a specific endocrine syndrome, which is similarly found in major depression. The aim of this study was to investigate whether visceral fat depots increase in depressed patients during a follow-up period explaining the increased risk for cardiovascular disorders. Intraabdominal fat was measured in 29 depressed patients and 17 controls by computer tomography at the level of lumbar vertebra 4. In patients fat measurements were done initially during a major depressive episode and again after a follow-up period of 14 months; in controls the mean time interval between measurements was 28 months. In both groups, saliva was taken at 800 h over a period of seven days prior to each CT for the estimation of free cortisol. In patients only, an oral glucose tolerance test was also carried out. Compared to controls hyper- and normocortisolemic depressed patients showed a larger accumulation of visceral fat mass over time (hypercort.:132.0 +/- 45 vs. 144.7 +/- 47 cm(2), p = 0.07; normocort.: 115.5 +/- 53 vs. 135.0 +/- 51 cm(2), p = 0.002; controls: 130.1 +/- 66 vs. 137.3 +/- 76 cm(2), p = 0.4), despite similar weight gain (hypercort.: 2.1 +/- 5 kg, normocort.: 1.7 +/- 5 kg and controls: 2.3 +/- 4 kg). Further, normocortisolemic patients showed a trend for an higher percentile increase in visceral fat accumulation than controls (23.9 +/- 27 vs. 5.8 +/- 28%, p = 0.07). At follow-up, free cortisol concentrations were still above normal in patients who had been hypercortisolemic at first assessment (35.0 +/- 8 vs. 28.8 +/- 18 nmol/l, p = 0.1). Fasting and 2 h glucose concentrations were higher in hypercortisolemic compared to normocortisolemic patients at the index examination (6.2 +/- 1.1 vs. 5.0 +/- 0.05 mmol/l, p = 0.02; 11.5 +/- 2.7 vs. 7.8 +/- 1.9 mmol/l, p = 0.01). The larger proportion of visceral fat accumulation in patients may constitute a link for explaining the increased cardiovascular mortality in patients suffering from major depression.

Adiposity↗
PubMed2005

Evidence for impaired cortical inhibition in patients with unipolar major depression.

BACKGROUND: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. METHODS: By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers. RESULTS: Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold. CONCLUSIONS: This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.

Adult↗
PubMed2005

Effects of right unilateral electroconvulsive therapy on motor cortical excitability in depressive patients.

Electroconvulsive therapy (ECT) is a widely acknowledged effective treatment for severe major depression. ECT produces considerable anticonvulsant effects that may be related to an increased GABA-ergic neurotransmission. We aimed to explore whether motor cortical excitability as assessed with single and paired pulse transcranial magnetic stimulation (TMS) could be used to investigate these anticonvulsant effects. Therefore, parameters of motor cortical excitability were investigated in 10 patients before and after 10 sessions of right unilateral ECT. After 10 sessions of right unilateral ECT, an enhanced activity of inhibitory circuits in human motor cortex had been observed, as measured by both increased intracortical inhibition and cortical silent period duration, whereas intracortical facilitation and resting motor threshold remained unchanged. The reduction of seizure duration in the course of ECT was associated with clinical improvement and an increase in intracortical inhibition. We interpret this finding as further indirect evidence for changes in inhibitory circuits in the course of ECT in patients with major depression.

Antidepressive Agents↗
PubMed2005

Substance P in serum and cerebrospinal fluid of depressed patients: no effect of antidepressant treatment.

The neuropeptide substance P (SP) and its receptor, the neurokinin receptor-1 (NK-1), have been associated with some aspects of the pathophysiology of depression. There is limited information available about the effects of antidepressant treatment on serum and cerebrospinal fluid (CSF) concentrations of SP. We measured serum levels of SP in 78 depressed patients after a 6-day medication washout period, as well as after 14 and 35 days of antidepressant treatment with either paroxetine or amitriptyline. In 11 patients, SP was determined in CSF both before and after treatment. Eleven healthy male subjects served as controls. Baseline SP concentrations were independent of age, gender and severity of depression. Neither the total group nor subgroups showed significant differences in SP serum concentrations. SP concentrations in CSF did not change significantly in the patients during treatment, but there was a trend for an increase in paroxetine-treated patients. Serum SP concentrations were not related to treatment response or the class of antidepressant administered. Our data do not support the hypothesis that changes in SP levels in serum or CSF are related to antidepressant response.

Adult↗
PubMed2005

Activity of the hypothalamus-pituitary-adrenal system and oral glucose tolerance in depressed patients.

We hypothesized that the activity of the hypothalamus-pituitary-adrenal system in depressed patients is related to oral glucose tolerance. In 70 moderately depressed inpatients, we measured morning saliva cortisol for 6 days and assessed oral glucose tolerance. We found glucose concentrations to be positively associated with mean morning cortisol concentrations (F3,236 = 2.86, p < 0.05). Also, the ISI, a measure of insulin receptor sensitivity, was negatively associated with mean morning cortisol concentrations (r = -0.25, p < 0.04). These findings support the hypothesis that hypercortisolemia may lead to disturbed glucose utilization in depressed patients.

Adult↗
PubMed2005

Cerebral blood flow during vagus nerve stimulation--a transcranial Doppler study.

BACKGROUND AND OBJECTIVES: Vagus nerve stimulation (VNS) is an approved treatment of partial onset seizures and has recently shown antidepressant effects in patients with treatment-resistant depression. This study was conducted to investigate whether acute VNS has an influence on cerebral blood flow (CBF) in humans. METHODS: This investigation was designed as an add-on study. In 10 patients with an implanted stimulator who participated in a multicenter clinical trial to evaluate the efficacy of VNS in depression, CBF was investigated by functional transcranial Doppler at baseline (before the stimulator was turned on for the first time) and during stimulation with three different stimulation intensities in a randomized order. RESULTS: Immediately after every increase of the current, CBF velocity showed a nonsignificant increase. Otherwise, no change of CBF above standard deviation could be registered. CONCLUSION: Acute VNS does not have an influence on CBF velocity in depressive patients.

Adult↗
PubMed2005

Age-related changes in sleep and memory: commonalities and interrelationships.

Aging is accompanied by changes on many different levels, including sleep and memory processes. In light of recent findings, which underline the importance of sleep for memory consolidation in young adults, the relationship between sleep and memory in older adults is of particular interest. This review takes a closer look at commonalities and interrelationships of the two aging trajectories in sleep and memory. A link between these two research domains on aging will be proposed and discussed on the basis of recent findings within the cognitive neuroscience of sleep.

Aged↗
PubMed2005

A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results.

The subproject 1.5 "Neurobiology of Suicidal Behavior" is a multicenter study assessing peripheral parameters of the serotonergic, noradrenergic, and dopaminergic transmitter systems. Additionally, stress hormones and the lipid system as well as inhibitory and excitatory amino acids will be investigated. The different parameters are collected in cerebral spinal fluid (CSF), blood, and saliva. Patients with a depressive spectrum disorder with and without a suicide attempt (during the last three weeks) and being medication free for two weeks are included in the study. So far, 103 patients and controls have been recruited. The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented.

Aggression↗