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Biomedical subjects

Ulrich Hegerl

Publications and source records attributed to Ulrich Hegerl.

At least 37 records · Page 2Linked to original sources

SERT and DAT availabilities under citalopram treatment in obsessive-compulsive disorder (OCD).

Serotonin and dopamine transporter (SERT, DAT) availabilities have prospectively been investigated using [123I]beta-CIT and single photon emission computed tomography in subjects with obsessive-compulsive disorder under treatment with the selective serotonin reuptake inhibitor citalopram. SERT availability decreased by a mean 36.5%, whereas DAT availability increased by about 40%. The data point at a citalopram induced modulation of both serotonergic and dopaminergic activity and support the notion of functional interactions of monoaminergic systems in the human brain.

Brain↗

[Kinematic movement analyses and their application in psychiatry].

There is a long tradition to develop valid instruments for the exact assessment of psycho-motor dysfunctions in psychiatry. However, progress is hampered by the complexity of emotionally driven movements in psychiatric patients. Methods used up to now either remains unspecific due to only qualitative measurements or focus on the neurophysiological aspects too much. Thus, the results accomplished so far are only very general unspecific concerning different groups of psychiatric patients. In this paper, two own methods are presented which are aimed to avoid the two poles above mentioned. Kinematic analyses of facial expressions as well as handwriting movements provide quantitative and quite specific informations about psycho-motor dysfunctions of psychiatric patients and the effects of psychotropic substances. Thus, these methods are well suitable for relating them to other neurobiological parameters in order to contribute to the pathophysiological understanding of psycho-motor symptoms in psychiatric patients.

Antipsychotic Agents↗

The German Research Network on Depression and Suicidality.

Under the common roof of the German Research Network on Depression and Suicidality, scientists, medical doctors, psychotherapists, and several of the most relevant institutions of the German health care system are aligned to proceed against the overlapping health problems of depression and suicidality. The project addresses professionals and scientists, affected patients and their relatives, and the total population at the same time. Comprehensive public relations activities contribute to an overall sensitization concerning the topics of depression and suicidality and inform about diagnosis and treatment options. The network is funded by the German Ministry of Education and Research and was established in 1999. Since then more than 20 individual projects have been initiated. Meanwhile more and more results of these projects become available and increasing efforts are undertaken to transfer these results into elements of standard health care.

Aged↗

How effective is advanced training concerning depression and suicidality among the elderly? Results of a pilot study.

Three Hundred and Seventy Four geriatric caregivers in Nuremberg and Munich participated in a four-hour advanced in-house training addressing the topic. "depression and suicidality in old age." Geriatric caregivers are key persons in early diagnosis of depressive symptoms and suicidality. The training focused on qualifying and sensitizing caregivers for these topics. A 12-item questionnaire was applied to measure the outcome parameters "knowledge and attitudes towards depression and suicidality in old age" within a pre-, post-, Three-months-follow-up design (rate of return = 58%). Short-term effectiveness of the advanced training "depression in old age" could be shown for most of the items. Significant long-term effects could be found concerning increase of knowledge about pharmacotherapy with antidepressants. Attitude towards "suicide in old age" also changed significantly. The training program was effective in improving knowledge and attitudes of geriatric caregivers concerning depression and suicidality.

Aged↗

Suicide prevention by lithium SUPLI--challenges of a multi-center prospective study.

Several studies have shown that there is a significantly increased risk of suicide related mortality in patients with a positive history of suicide attempts. The SUPLI-Study is the first prospective, randomized, double blind, placebo controlled multi-center trial focusing on the proposed suicide preventive effects of lithium in patients with suicidal behavior but not suffering from bipolar disorder or recurrent major depressive disorder. Patients with a recent history of a suicide attempt are treated with lithium versus placebo during a 12 month period. The hypothesis is that lithium treatment will lead to a 50% reduction of suicidal behavior. The protocol of the study and preliminary results are presented.

Antipsychotic Agents↗

Evidence for a close relationship between conscious effort and anterior cingulate cortex activity.

The function of the anterior cingulate cortex (ACC) has been discussed in the last years in the context of conflict monitoring and error detection. In addition, ACC activity has been described in the context of "conscious effort". Recent neurophysiological and neuroimaging studies have described a negative correlation between ACC activity and reaction times in simple or choice reaction time experiments. One suggested explanation for this finding has been that there is a relationship between effort and ACC activity. The present ERP-LORETA study of healthy volunteers (n=35) was intended to directly investigate this relationship. In this experiment, three conditions were investigated: condition I was a choice reaction task with the instruction to stay relaxed during the task (relaxed condition), condition II was the same choice reaction task with the instruction to press the respective button as fast and correct as possible (effort condition). Condition III was just listening to the tones without button press (control condition). Subjects had to score directly after each experimental run on a visual analogue scale the amount of effort they have actually spent. The subjects showed significantly shorter reaction times during the high effort condition in comparison to the relaxed condition, as well as increased N1 amplitudes and increased ACC activity. In a subgroup analysis, this effect was present only in subjects who were (according to their self-ratings) following the instructions closely. These results provide direct evidence for a close relationship between conscious effort and ACC activity and suggest the usefulness of the applied effort-self-rating.

Adult↗

Differential effects of reboxetine and citalopram on hand-motor function in patients suffering from major depression.

RATIONALE: Motor dysfunctions might be a more common side effect of serotonergic than noradrenergic antidepressants. However, the effects of antidepressants on motor function in depression have rarely been analyzed systematically. Computerized methods allow the objective registration of drug-induced motor dysfunction and were applied in this study. OBJECTIVES: To examine the effects of a selective noradrenaline re-uptake inhibitor (NARI) (reboxetine) and a selective serotonin re-uptake inhibitor (SSRI) (citalopram) on hand-motor function in patients with major depression. METHODS: Different types of hand movements (drawing of circles and handwriting probes) were recorded and analyzed in 16 acutely depressed inpatients receiving citalopram (30-60 mg/day) and 12 acutely depressed inpatients treated with reboxetine (4-8 mg/day), using a digitizing tablet for the analysis of movement dynamics. Both groups were comparable regarding mean age (42-43 years), gender, handedness (preponderance of right-handers) and the mean baseline HAMD score (about 27). Five kinematical parameters reflecting velocity, regularity and degree of automation of hand movements have been computed. RESULTS: Reboxetine had significantly more favorable effects on fine motor function (increased velocity of rapid hand movements) in depressed patients than citalopram. These differences became obvious when patients conducted more complex tasks and are not explained by differential antidepressant effects. CONCLUSIONS: Our findings are in line with the hypothesis that SSRI tend to have small, but more pronounced negative effects on motor function than NARI.

Acute Disease↗

The gamma amino butyric acid (GABA) receptor alpha-3 subunit gene polymorphism in unipolar depressive disorder: a genetic association study.

There is evidence that genes coding for the gamma aminobutyric acid (GABA) receptor may be involved in the etiology of affective disorders. Recently, an association between a CA-repeat in the GABRA 3 gene and bipolar disorder had been reported. The present study aimed at investigating the association between this polymorphism and unipolar major depressive disorder. The sample consisted of 201 unipolar depressive patients and 151 healthy subjects. All study participants were unrelated German individuals of the same ethnogeographical origin. No differences in genotype frequencies between unipolar patients and healthy subjects were found for GABRA 3 (P = 0.08). However, a significant difference of allelic frequencies was observed in female patients (n = 128) compared to female controls (n = 81) (P < or = 0.0001). This effect was not present in the group of male patients (n = 73) compared to male healthy subjects (n = 70) (P = 0.24). The results of our study indicate that GABRA 3 gene might also be involved in the genetic pathophysiology of unipolar major depressive disorder (at least in female patients), even if the findings do not support a predominant role of GABRA 3.

Adult↗

Screening for depression in primary care: will one or two items suffice?

Small differences in implementation of screening and the associated burden on clinicians and patients could have substantial effects on the sustainability of screening in routine primary care. Therefore, we investigated the psychometric properties of single items and two-item combinations of the "WHO-5 Well Being Index" (WHO-5) and compared the obtained characteristics to those of the original version as well as to another proposed two-item screener (developed from PRIME-MD and BPHQ, respectively). Screening and diagnostic interview data from 431 primary care patients were analysed. Main outcome measures were sensitivity, specificity and AUC values. All test characteristics were assessed using the diagnoses derived from the Composite International Diagnostic Interview (CIDI) as the criterion standard.Single-item screening questions proved rather inadequate. However, only marginal differences in performance were found between two questions and the longer screening instrument with respect to major depression, dysthymia and "any depressive disorder". There were no statistically significant differences between these AUC values and most other test characteristics assessed. The results suggest that screening could be reduced to two questions with a potential advantage in terms of ease of administration and scoring and decreased staff and patient burden and perhaps a reduced stigma associated with a positive screening score.

Aged↗

Should combined pharmaco- and psychotherapy be offered to depressed patients? A qualitative review of randomized clinical trials from the 1990s.

Focusing on recent publications from the 1990s, this article qualitatively reviews the comparative efficacy of the combination of pharmaco- and psychotherapy (COMBI) vs either modality alone. There is only a weak empirical basis recommending the routine use of both psychotherapy and pharmacotherapy in acute treatment of Major Depressive Disorders (MDD). Concerning long-term treatment of MDD patients, the methodologically sophisticated study from Frank et al. shows that a COMBI is superior to interpersonal psychotherapy but not superior to medication alone. However, certain subgroups of patients might benefit substantially from COMBI compared to both psychotherapy and pharmacotherapy alone: 1) acute and long-term treatment of more severe forms of chronic depression, and 2) long-term treatment of older MDD patients. Compared to psychotherapy alone, severely depressed MDD patients profit more and faster when treated with combined psycho-pharmacotherapy.

Antidepressive Agents↗

Depression with atypical features in a sample of primary care outpatients: prevalence, specific characteristics and consequences.

BACKGROUND: In the context of the current debate on the clinical relevance of atypical depression, the present study investigated the prevalence and specific characteristics of the disorder in depressed primary care outpatients and compared patients with atypical and with the prototypical form of depression ("non-atypical" depression). METHODS: 403 patients were examined using the Composite International Diagnostic Interview, Inventory of Depressive Symptomatology, Hamilton Depression Scale and DSM-IV criteria. Configurational frequency analyses (CFA) were conducted to identify non-random configurations of symptoms. Moreover, tests for independent sample comparisons were applied. RESULTS: The prevalence of atypical depression in our sample of depressed patients was 26.3%. CFA revealed one significant symptom pattern: mood reactivity without additional atypical features (p<0.000001). A significant difference emerged between patients suffering from atypical versus non-atypical depression in terms of severity (p< or =0.001). LIMITATIONS: The sample size was modest. CONCLUSIONS: A considerable proportion of depressed primary care outpatients may suffer from atypical depression which may contribute to under-recognition of depression in primary care. Results of CFA indicated the significance of mood reactivity which may also occur in depressed patients without additional atypical symptoms. Patients with atypical depression may suffer from less severe depression as compared to patients with non-atypical depression.

Adult↗

Integration of fMRI and simultaneous EEG: towards a comprehensive understanding of localization and time-course of brain activity in target detection.

fMRI and EEG are complimentary methods for the analysis of brain activity since each method has its strength where the other one has limits: The spatial resolution is thus in the range of millimeters with fMRI and the time resolution is in the range of milliseconds with EEG. For a comprehensive understanding of brain activity in target detection, nine healthy subjects (age 24.2 +/- 2.9) were investigated with simultaneous EEG (27 electrodes) and fMRI using an auditory oddball paradigm. As a first step, event-related potentials, measured inside the scanner, have been compared with the potentials recorded in a directly preceding session in front of the scanner. Attenuated amplitudes were found inside the scanner for the earlier N1/P2 component but not for the late P300 component. Second, an independent analysis of the localizations of the fMRI activations and the current source density as revealed by low resolution electromagnetic tomography (LORETA) has been done. Concordant activations were found in most regions, including the temporoparietal junction (TPJ), the supplementary motor area (SMA)/anterior cingulate cortex (ACC), the insula, and the middle frontal gyrus, with a mean Euclidean distance of 16.0 +/- 6.6 mm between the BOLD centers of gravity and the LORETA-maxima. Finally, a time-course analysis based on the current source density maxima was done. It revealed different time-course patterns in the left and right hemisphere with earlier activations in frontal and parietal regions in the right hemisphere. The results suggest that the combination of EEG and fMRI permits an improved understanding of the spatiotemporal dynamics of brain activity.

Acoustic Stimulation↗

Serotonin and dopamine transporter availabilities correlate with the loudness dependence of auditory evoked potentials in patients with obsessive-compulsive disorder.

Brain monoaminergic function is involved in the pathophysiology of psychiatric disorders. The loudness dependence (LD) of the N1/P2 component of auditory evoked potentials has been proposed as a noninvasive indicator of central serotonergic function, whereas single photon emission computed tomography (SPECT) and [123I]beta-CIT can be used to visualize both serotonin (SERT) and dopamine transporters (DAT). The aim of the study was to correlate LD and SPECT measures in patients with obsessive-compulsive disorder, a condition with evidence for a serotonergic dysfunction. A total of 10 subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities. The LD of the relevant subcomponents (tangential dipoles) was investigated using dipole source analysis. SPECT was performed 20-24 h after injection of a mean 140 MBq [123I]beta-CIT. As a measure of brain SERT and DAT availabilities, a ratio of specific to nonspecific [123I]beta-CIT binding for the midbrain . pons region (SERT) and the striatum (DAT) was used. The LD of the right tangential dipole correlated significantly with both SERT and DAT availabilities (Pearson's correlations: rho = 0.69, p < 0.05, and rho = 0.80, p < 0.01, respectively). The correlations remained significant after controlling for the effects of age, gender, and severity of clinical symptoms. Associations between LD and both SERT and DAT availabilities further validate the use of neurophysiological approaches as noninvasive indirect measures of neurochemical brain function and point at a hypothesized interconnection of central monoaminergic systems.

Acoustic Stimulation↗

Kinematical analysis of motor function in schizophrenic patients: a possibility to separate negative symptoms from extrapyramidal dysfunction induced by neuroleptics?

BACKGROUND: In this prospective matched case-control study, hand movement analysis was conducted using a digitizing tablet (kinematical analysis). METHODS: The study examined the association of different computer-assessed hand movement variables with clinical pathology (negative symptoms and extrapyramidal motor dysfunction). A sample of 16 schizophrenic patients and 16 healthy controls participated in the study. RESULTS: At baseline, kinematical analysis indicated a significant higher prevalence of subtle hand motor dysfunction in unmedicated schizophrenic patients (who all exhibited clinically no extrapyramidal dysfunction) in comparison to healthy controls. No association between the observed motor signs and pre-enrollment total long-term butyrophenones exposure has been detected. After 14 days treatment with haloperidol, the hand movement variables, which correlated significantly with clinical rating scores reflecting drug-induced extrapyramidal dysfunction could definitely be separated from the hand movement variables with a close association to clinical rating measuring negative symptoms. CONCLUSIONS: Results of the comparative analysis at baseline confirm previous findings concerning presence of neurological soft signs in unmedicated schizophrenic patients. Furthermore, results of this pilot study suggest that kinematical analysis by means of a digitizing tablet could be a useful approach towards a differentiation between drug-induced akinetic symptoms and disease-induced negative symptoms.

Adult↗

Elevated brain serotonin transporter availability in patients with obsessive-compulsive disorder.

BACKGROUND: A central serotonergic dysfunction is considered to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate the serotonin transporter availability in patients with OCD as an in vivo marker of the central serotonergic system. METHODS: Nine unmedicated (7 drug-naive) patients with OCD and 10 healthy control subjects were included and received single photon emission computed tomography (SPECT) 20.75 +/- 1.51 hours after injection of a mean 147.20 +/- 6.74 MBq [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT). As a measure of brain serotonin transporter availability, a ratio of specific-to-nonspecific [(123)I]beta-CIT binding for the midbrain-pons (V(3)" = [midbrain/pons-occipital]/occipital) was used. RESULTS: Mean specific-to-nonspecific ratios showed a 25% higher midbrain-pons [(123)I]beta-CIT binding in the patients as compared with healthy controls (2.26 +/-.37 vs. 1.81 +/-.23, p <.01). The difference remained significant after adjustment for clinical variables and controlling for age and gender. Stratification of the patients according to onset of the disorder revealed significant differences between controls and patients with early (childhood, adolescence) but not late (adult) onset of OCD. CONCLUSIONS: The study provides evidence of a serotonergic dysfunction in patients with OCD and suggests a serotonergic component in the pathophysiology of the disorder.

Adult↗