PubMed Health⌕ Search

Biomedical subjects

Christoph Mulert

Publications and source records attributed to Christoph Mulert.

At least 19 recordsLinked to original sources
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

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

Is the loudness dependence of auditory evoked potentials modulated by the selective serotonin reuptake inhibitor citalopram in healthy subjects?

The loudness dependence of auditory evoked potentials (LDAEP) has been discussed as a non-invasive in vivo marker of central serotonergic function. Evidence for this has been found in animal studies, but studies in humans provide less consistent results. In this study, the relationship between LDAEP and directly modulated central serotonergic activity in healthy subjects was investigated. In a single-blind cross-over design, the LDAEP of female participants (age: 24.0 +/- 2.3 years) was measured under two conditions: (1) infusion of 20 mg citalopram diluted in 250 ml 0.9% saline and (2) infusion of 250 ml 0.9% saline as placebo. LDAEP was measured at five different time points before, during and up to 60 min after drug/placebo administration and dipole source analysis was performed. The increase of the central serotonin activity in response to citalopram was not accompanied by a significant change of the LDAEP compared to the placebo condition. The result underlines that the acceptance of LDAEP as a marker of central serotonergic function still needs further discussion.

Acoustic Stimulation↗
PubMed2006

A Ser9Gly polymorphism in the dopamine D3 receptor gene (DRD3) and event-related P300 potentials.

An important reason for the interest in P300 event-related potentials are findings in patients with psychiatric disorders like schizophrenia or alcoholism in which attenuations of the P300 amplitude are common findings. The P300 wave has been suggested to be a promising endophenotype for genetic research since attenuations of the amplitude and latency can be observed not only in patients but also in relatives. In parallel, the search for genes involved in the pathogenesis of psychiatric disorders has revealed for both, schizophrenia and alcoholism an association with a DRD3 Ser9Gly polymorphism in a number of studies. In the present study, we have investigated 124 unrelated healthy subjects of German descent and have found diminished parietal and increased frontal P300 amplitudes in Gly9 homozygotes in comparison to Ser9 carriers. This finding suggests a possible role of the DRD3 receptor gene in the interindividual variation of P300 amplitudes. Further studies should address the direct role of the DRD3 Ser9Gly polymorphism in attenuated P300 amplitudes in psychiatric disorders like schizophrenia or alcoholism.

Acoustic Stimulation↗
PubMed2006

Event related potentials and fMRI in neuropsychopharmacology.

Event related potentials (ERP) are important clinical and research instruments in neuropsychiatry, particularly due to their strategic role for the investigation of brain function. These techniques are often underutilized in the evaluation of neurological and psychiatric disorders, but nevertheless they can be most useful and highly effective in the diagnostic workup of a wide range of neuropsychiatric disorders as well as in monitoring the course of the disorders and the prediction of treatment responses. ERP are noninvasive instruments that directly reflect cortical neuronal activity. Cortical neuronal dysfunction plays a major role in variable neuropsychiatric disorders, and a change in cortical activity under medication might reflect treatment response and could be useful for monitoring drug effects. ERP are the only methods with a sufficiently high time resolution for the analysis of the dynamic patterns of neuronal brain activity, e.g., synchronization and desynchronization, oscillations, coherence, gamma band activity, latency of event related activity, etc., which are crucial for a deeper understanding of functional (neurophysiological) correlates of cognitive, emotional and behavioral disturbances in neuropsychiatric patients. Methodological advances have further improved and strengthened the position of ERP concerning research and clinical application. The usefulness and applicability of ERP in determining and monitoring clinico-pharmacological effects will be summarized mainly by focussing on the auditory evoked P300 and the N1/P2 component of auditory evoked potentials. Owing to important recent developments in the field of brain functional diagnostics the combination of neurophysiological techniques and functional magnetic resonance imaging (fMRI) will be included.

Brain↗
PubMed2005

Striatal dopamine release after prefrontal repetitive transcranial magnetic stimulation in major depression: preliminary results of a dynamic [123I] IBZM SPECT study.

Though there is considerable evidence that prefrontal repetitive transcranial magnetic stimulation (rTMS) exerts antidepressant effects, the neurobiological action of rTMS in patients with depression is poorly understood. Preclinical studies in animals and humans have demonstrated that prefrontal rTMS can induce dopamine release in mesostriatal and mesolimbic regions. We therefore investigated whether rTMS also modulates striatal dopaminergic neurotransmission in depressed patients using a dynamic [123I] iodobenzamide (IBZM) single photon emission computed tomography (SPECT) approach. Five patients with a major depressive episode (DSM-IV) underwent an acute 10 Hz rTMS challenge with 3000 stimuli over the left dorsolateral prefrontal cortex during an [123I] IBZM-SPECT bolus and constant infusion protocol. In four subjects the protocol was repeated after a three week rTMS standard treatment. Striatal IBZM binding to dopamine D2 receptors was assessed with a region-of-interest (ROI) technique. The change in striatal IBZM binding after the rTMS challenge was regarded as measure of change in endogenous striatal dopamine. Data of nine SPECT investigations showed a significant reduction by 9.6+/-6.2% in IBZM binding to striatal dopamine D2 receptors after rTMS challenge compared to baseline (p=0.01, Wilcoxon test). In this preliminary study, the reduction of IBZM binding observed after rTMS challenge is suggestive of a release in endogenous dopamine induced by prefrontal rTMS. In future, this approach can be used to differentiate specific and non-specific reward-related effects of rTMS on dopaminergic neurotransmission.

Aged↗
PubMed2005

Sound level dependence of the primary auditory cortex: Simultaneous measurement with 61-channel EEG and fMRI.

Sound level dependence has been investigated for years with event-related potentials (ERP). A serotonergic modulation of the sound level dependence only of the primary auditory cortex but not of the auditory association cortex has been suggested by a number of clinical and preclinical studies. Therefore, a precise covering of the activity of the primary auditory cortex seems necessary if sound level dependence is used as an indicator of the central serotonergic system. Recent fMRI studies described a pronounced sound level dependence only in the Heschl gyrus/primary auditory cortex but not in auditory association areas. In the present simultaneous 61-channel EEG and fMRI study investigating fourteen healthy subjects, we found a high correlation between the loudness-dependent change of the extent of fMRI activation (number of activated voxels) and the corresponding changes of the mean current source density within the same region of interest covering the primary auditory cortex (r = 0.84, P < 0.001). Our findings suggest a close relationship between the fMRI signal and event-related potential activity. In addition, the correspondence of the ERP-based data and the fMRI results further supports the validity of the ERP localization approach.

Acoustic Stimulation↗
PubMed2005

Electrophysiological and neuropsychological analysis of a delirious state: the role of the anterior cingulate gyrus.

Functional neuroimaging studies in humans have provided evidence that a frontal network including the anterior cingulate cortex (ACC) plays an important role in attention and awareness. Disturbed attention and awareness are core symptoms of delirium, but imaging studies of attentional dysfunctions in delirium are lacking. However, an increase of slow electroencephalographic (EEG) activity (delta, theta) is a consistent biological finding in delirium. The question whether this slow activity is related to a disturbance in the frontal attentional network has not yet been addressed. The delirium after electroconvulsive therapy (ECT) has been investigated using 32-channel resting EEG before and shortly after ECT in 12 patients with major depressive disorder. During delirium compared with baseline studies, substantial increases of delta and theta power and a decrease of alpha power were observed. The decrease of theta activity at the Fz electrode position in the following 24 h was significantly related to the recovery of awareness and performance of free recall. Source analysis with Low Resolution Electromagnetic Tomography (LORETA) indicated that the main generators of the theta excess during delirium were significantly localized in the anterior cingulate cortex, and additionally in right fronto-temporal brain areas. The results support the concept that a disturbance of attention and awareness during delirium is related to a dysfunction of an attentional network involving the ACC. However, the localization of the theta excess may reflect some motor dysfunctions as well. This dysfunction of the ACC was shown for the first time in patients during a delirious state and may represent an important pathophysiological aspect of delirium.

Attention↗
PubMed2005

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2004

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↗
PubMed2003

EEG abnormalities associated with antipsychotics: a comparison of quetiapine, olanzapine, haloperidol and healthy subjects.

In this study the effects of the atypical antipsychotics quetiapine and olanzapine, and the typical antipsychotic haloperidol on EEG patterns were retrospectively investigated in 81 patients under stable monotherapy with either drug (quetiapine: n=22, olanzapine: n=37, haloperidol: n=22). These three subgroups were compared with a control group of healthy subjects (n=30) which were matched regarding sex and age. Diagnoses of patients were schizophrenia (DSM-IV 295.xx, n=61), brief psychotic disorder (DSM-IV 298.8, n=9), schizoaffective disorder (DSM-IV 295.70, n=8) and delusional disorder (DSM-IV 297.1, n=3). There were no statistically significant differences regarding demographic characteristics between the groups. Digital EEG recordings were retrieved from a database and visually assessed by two independent investigators, and one blinded regarding medication. One patient from the quetiapine group (5%), 13 olanzapine patients (35%), five of the haloperidol patients (23%) and two subjects of the control group (7%) had an abnormal EEG. Epileptiform activity was observed in four patients (11%) of the olanzapine group, and none in the others. EEG abnormalities were statistically significantly increased with dose in the olanzapine group, in contrast to patients treated with haloperidol, quetiapine or healthy subjects. In conclusion, EEG abnormalities seem to occur rarely in patients treated with quetiapine comparable to the control group, but significantly more often with haloperidol and olanzapine, possibly due to different receptor profiles of these substances. To our knowledge, this is the first electrophysiological investigation comparing the new atypical antipsychotics quetiapine, haloperidol, olanzapine with healthy subjects.

Adolescent↗
PubMed2003

The relationship between reaction time, error rate and anterior cingulate cortex activity.

Current concepts of cognitive control suggest that the anterior cingulate cortex (ACC) is involved in performance monitoring. This idea is supported by the finding that increased ACC activity is found in situations in which errors are likely to occur, even if none are actually made. In addition, recent results suggest that increased ACC activity is negatively correlated with reaction time. We have now compared the error rates and the ACC activity of healthy subjects with short (n=19) vs. long reaction times (n=17) in an auditory choice reaction paradigm and analysed the current density differences in the ACC in the time range of the N1 component with low resolution electromagnetic tomography. Subjects with short reaction times showed significantly more ACC activation (Brodmann Area 24) and an increased error rate. This finding suggests that increased ACC activity is associated with a gain in reaction speed at the expense of correctness and is discussed in the context of current concepts about the role of the ACC in cognitive functions.

Acoustic Stimulation↗
PubMed2003

[Agreement in physicians' and patients' assessment of depressive disorders].

Depression is one of the most frequently encountered mental health disorders in primary care. The health and financial burden caused by this disorder emphasise the clinical importance of depressive disorders. Research shows that these conditions often remain unrecognised and untreated. The aim of this study is to analyse if and how primary care physicians identify this condition in comparison to the patients' self-evaluation. A total of 1,233 cases in 32 primary care physicians' offices were examined to see if symptoms of depression were recognised. The assessment procedures were evaluated, too. In this study, the prevalence of depressive disorders was 10%, and the recognition rate of primary care physicians 45%. These results underscore the importance of improving physicians' recognition of depression and use of ICD-10 criteria for differential diagnosis. Conclusions must be drawn for a specific training of primary care physicians that focuses on the improvement of diagnosis and treatment of depressed patients.

Depressive Disorder↗
PubMed2003

[Subjectively-perceived inappropriate treatment of depressed patients in general and psychiatric practice].

In the present study, process quality in outpatient depression care was documented by general practitioners and specialists in psychiatry. Opportunities to improve inpatient treatment were identified by comparing current physicians' treatment procedures with guideline recommendations and, furthermore, by evaluating treatment outcomes from the patients' perspective. Data of 350 depressed outpatients were collected by 43 GPs and 23 specialists in psychiatry in three study regions (Rhineland, South Baden and Munich). Data reflected psychopathology, diagnostic assessment, investigation of suicidal intentions as well as somatic and psychotherapeutic measures at the first visit. Additionally, change in depression symptoms after six to eight weeks by means of self-rating (n = 165) and expert rating (n = 70) was measured. The study shows that the GPs and, to a lesser extent, the specialists, still fail to orient themselves towards guideline recommendations regarding assessment, therapy and referral in depression care. These findings seem to be reflected in insufficient self rated treatment outcome: one half of the patients reported a reduction in depression symptoms, the other half of patients reported stagnation or even progression. Expert ratings of treatment courses were more positive. The results indicate a considerable need for guideline training and improvement of networking and co-operation between GPs and specialists as well as between inpatient and outpatient settings.

Depressive Disorder↗
PubMed2002

Cortical hypoactivation during resting EEG in schizophrenics but not in depressives and schizotypal subjects as revealed by low resolution electromagnetic tomography (LORETA).

This study was performed in order to address the question whether the newly introduced technique of low-resolution electromagnetic tomography (LORETA) is able to detect hypofrontality in schizophrenic patients. We investigated resting EEGs of 19 unmedicated schizophrenics and 20 normal subjects. For comparison, we also investigated 19 subjects with schizotypal personality and 30 unmedicated depressive patients. A significant increase of delta activity was found in schizophrenic patients over the whole cortex, most strongly in the anterior cingulate gyrus and temporal lobe (fusiform gyrus). Both schizotypal subjects and depressive subjects showed significantly less delta, theta and beta activity in the anterior cingulum, a decrease of alpha1 activity in the right temporal lobe and a decrease of alpha2 activity in the left temporal lobe. The results suggest general cortical hypoactivation, most pronounced in the anterior cingulate and temporal lobe in schizophrenics, whereas there is evidence for a complex, frequency-dependent spatial pattern of hyperactivation in schizotypal subjects and depressive patients. The results are discussed within a neurophysiological and methodological framework.

Adult↗