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Biomedical subjects

U Hegerl

Publications and source records attributed to U Hegerl.

At least 91 records · Page 5Linked to original sources

[Behavior therapy competence training--a specific intervention with beginning Alzheimer dementia].

At the Psychiatric Department, Ludwig-Maximilians-Universität, Munich, a behavioral competency training (Verhaltenstherapeutisches Kompetenztraining) VKT is offered to patients with early stages of Alzheimer's disease (AD). The primary objects of VKT are, (a) patient support in coping with the diagnosis of AD, (b) mobilization of the present personal activity resources, and (c) minimization of depressive symptoms. The VKT consists of six therapy-modules: 1. behavior analysis, 2. psychoeducation, 3. stress management, 4. increase of pleasant activities, 5. enhancement of social competency, and 6. modification of depressive cognitive patterns. The VKT is derived from scientific findings that show the involvement of psycho-social factors in the genesis of AD. Inadequate coping-behavior, unescapable stress and resulting neurodegenerative effects, a low premorbid niveau of activity and the presence of premorbid depressive symptoms outline the necessity of psychotherapeutic treatment in AD patients.

Activities of Daily Living↗

The serotonin syndrome scale: first results on validity.

As a modification of the diagnostic criteria of the serotonin syndrome proposed by Sternbach, we developed the Serotonin syndrome scale for the operationalized assessment of both the presence and the severity of the core symptoms of the serotonin syndrome. In a first study on the validity of this scale, the relationships between the serotonin syndrome score (SSS) and both the paroxetine plasma levels (n = 42) and the loudness dependence of the auditory evoked potentials (LDAEP; n = 24) were investigated in depressed patients treated with paroxetine. A strong LDAEP is supposed to indicate low central serotonergic neurotransmission, and vice versa. The SSS was positively related to paroxetine plasma levels and negatively to the LDAEP. Both results support the validity of the serotonin syndrome scale. Using a SSS > 6 as diagnostic criterion, mild serotonin syndromes were diagnosed in 5 of our 42 patients. The Serotonin syndrome scale may become a useful tool for clinicians and scientists dealing with the serotonin syndrome.

Adult↗

Markers from event-related potential subcomponents and reaction time for information processing dysfunction in schizophrenia.

Event-related potentials (ERPs) can serve as markers for cognitive processing stages. Identification of those ERPs altered in schizophrenia offer information about cognitive dysfunction. Auditory evoked potentials (AEPs) were elicited within an oddball paradigm in 35 schizophrenic patients and compared with 35 healthy controls. N100 and P200, as well as N200, frontal P300 and parietal P300 subcomponents, were separated using dipole source analysis. The amplitudes of the N100 and the parietal P300 measured in schizophrenics were diminished. The input-related processing stages (N100 and P200) were not altered, whereas later, the deviant and task-related processes (N200, frontal P300, parietal P300 and reaction time) were significantly prolonged in schizophrenia.

Adult↗

Double-blind, multicenter comparative study of sertraline and amitriptyline in hospitalized patients with major depression.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) for which marketing approval has been obtained recently in Germany. The results of several double-blind, placebo-controlled studies have demonstrated that sertraline has a clear antidepressive effect. However these studies have been conducted in outpatient populations. In the context of this multicenter study, a total of 160 inpatients were treated with sertraline 50-150 mg or amitriptyline 75-225 mg over a period of 6 weeks in a double-blind fashion. Sixty-two patients in the sertraline and 59 patients in the amitriptyline group were evaluated for efficacy in the according-to-protocol (ATP) population; 80 sertraline and 75 amitriptyline patients were evaluated for safety in the Intention-to-treat population (ITT). No statistically significant differences were detected between the two groups in the efficacy analysis performed on the basis of the Hamilton Depression Scale (HAM-D) total score and Clinical Global Impression (CGI). Due to its sedating properties, amitriptyline was found to be significantly more effective with regard to the HAM-D factor "sleep disturbance". The safety analysis, which was based on the CGI, the global assessment at the end of study and a score for somatic adverse events (FSUCL) revealed statistically significant advantages of sertraline over amitriptyline. Amitriptyline was associated with more autonomic and circulatory side effects, while epigastric complaints occurred more often with sertraline. The incidence of nausea - a typical SSRI side effect - was the same in both groups.

Adrenergic Uptake Inhibitors↗

Auditory-evoked potentials as indicator of brain serotonergic activity--first evidence in behaving cats.

Due to the increasing importance of the central serotonergic neurotransmission for pathogenetic concepts and as a target of pharmacotherapeutic interventions in psychiatry, reliable indicators of this system are needed. Several findings from basic and clinical research suggest that the stimulus intensity dependence of auditory evoked potentials (AEP) may be such an indicator of behaviorally relevant aspects of serotonergic activity (Hegerl and Juckel 1993, Biol Psychiatry 33:173-187). In order to study this relationship more directly, epidural recordings over the primary and secondary auditory cortex were conducted in chronically implanted cats under intravenous (i.v.) administration of drugs influencing the serotonergic and other modulatory systems (8-OH-DPAT, m-CPP, ketanserin, DOI, apomorphine, atropine, clonidine). The intensity dependence of the cat AEP component with the highest functional similarity to this of the N1/P2-component in humans was significantly changed by influencing 5-HT1a and 5-HT2 receptors, but not 5-HT1c receptors. This serotonergic modulation of the intensity dependence was only found for the primary auditory cortex which corresponds to the known different innervation of the primary and secondary auditory cortex by serotonergic fibers. Our study supports the idea that the intensity dependence of AEP could be a valuable indicator of brain serotonergic activity; however, this indicator seems to be of relative specificity because at least cholinergic effects on the intensity dependence were also observed.

Animals↗

Dipole source analysis of P300 component of the auditory evoked potential: a methodological advance?

A dipole model of the P300 component of the auditory evoked potential was developed with the aim of separating the overlapping P300 subcomponents and assessing the reliability of P300 dipole parameters compared with other methods such as principal component analysis (PCA). P300 was recorded within an auditory oddball paradigm in 57 healthy subjects. Dipole source analysis was performed with Brain Electrical Source Analysis (BESA). With a temporo-basal and a temporo-superior dipole per hemisphere, most of the variance of scalp-recorded P300 activity can be explained. When dipole source analysis is used, the test-retest reliability of P300-amplitude measurements is enhanced as compared with PCA or single channel analysis. The P300 activity of the temporo-basal dipoles and that of the temporo-superior dipoles differ in several respects (e.g. latency, correlations with age) and thus appear to reflect functionally different neuronal processes. In spite of problems in the interpretation of dipole locations, it is concluded that dipole source analysis enhances both the reliability and physiological validity of P300 parameters.

Adolescent↗

Electroencephalography as a diagnostic instrument in Alzheimer's disease: reviews and perspectives.

Electroencephalography is the only diagnostic instrument directly reflecting cortical neuronal functioning, and it remains an important clinical tool in the diagnosis and differential diagnosis of Alzheimer's disease (AD). Although a normal EEG is found in many patients with mild AD, a pathological EEG is an important finding, because such a result is not in line with differential diagnoses such as depression or pseudodementia within a dissociative disorder. The vast majority of patients with moderate to severe AD have a pathological EEG. A normal EEG in this patient group is more in line with subcortical dementia or frontal lobe degeneration than with AD. Compared to SPECT or routine structural brain imaging (cCT, MRT), EEG has a comparable diagnosis sensitivity and a higher specificity. For monitoring changes of brain function by serial recordings (e.g., during therapy with antidementia drugs), EEG is the best available method.

Aged↗

Dipole localization and test-retest reliability of frequency and duration mismatch negativity generator processes.

The mismatch negativity (MMN) is an event related potential component elicited by changes in duration, frequency or intensity of the stimuli during repetitive series of equal standard stimuli. In the present study we compared duration and frequency MMN using dipole source analysis concerning both the test-retest reliability of MMN-amplitudes and the locations of the potential sources. Furthermore, the influence of attention for test-retest-reliability was studied. Therefore, two groups of healthy subjects were investigated with different attentional manipulations. Twenty-one healthy subjects had to perform a visual attention task during the recording and 21 healthy subjects had no additional task to perform. All subjects were studied twice with a time interval of 3 weeks. Test-retest reliability was sufficiently high for the frequency but slightly lower for the duration MMN. The locations of the frequency and duration MMN-dipoles were in the auditory cortex with a more anterior and caudal location for the frequency MMN-dipoles. The latter finding supports the hypothesis that the frequency and duration MMNs have separate neuronal generators.

Adult↗

The AMDP modules I-IV: recommendations for a standardized acquisition of EEG data in psychiatry. Association for Methodology and Documentation in Psychiatry.

During the last few years, the working group 'Psychophysiology' of the Association for Methodology and Documentation in Psychiatry (AMDP) discussed the possibility of the establishment of defined EEG modules in psychiatry. It was the aim to create a common data pool in order to be able to have access to larger data sets. The installation of such a common data pool was regarded as an important prerequisite for a future diagnostic application of EEG and EP data in clinical practice. The most relevant arguments are: From a statistical point of view, multivariate investigations can be improved when relatively large data sets are available. Subgrouping of patients is facilitated. Different centers have access to different populations of patients. Furthermore, compliance with the recommendations contributes to a reduction in misunderstanding and false interpretation of other investigators' results. The working group 'Psychophysiology' of the AMDP now recommends EEG modules to be registered in psychiatry. The recommendations are based on investigations using these modules in clinical research and practice as well as several years of discussion within the working group. Four AMDP modules (I-IV) are presented: MI: resting EEG (closed eyes), MII: resting EEG (eyes open), MIII: EEG during videotracking, and MIV: EEG during choice reaction time. Recommendations for additional modules are planned in the near future: MV: EEG during geometry test, MVI: EEG during labyrinth test, and MVII: amplitude stimulus intensity function. MIII-MVI is paralleled by an EEG recording so that psychomotor performance can be measured and EEG data under different activation conditions are available. Compliance with the recommendations guarantees the possibility of access to the common data pool. Computer software is available in Berlin.

Electroencephalography↗

Residual symptoms and P300 in schizophrenic outpatients.

A reduced P300 amplitude has often been found to be related to schizophrenic psychopathology. It is still unclear, however, whether this relationship is trait- or state-dependent. We investigated 88 stabilized schizophrenic outpatients during a 2-year follow-up period. Multivariate analyses revealed that patients who had reduced P300 amplitudes showed pronounced residual symptoms, especially thought disorder (Brief Psychiatric Rating Scale). Intraindividual changes in that psychopathology were not correlated to corresponding changes of the P300 amplitude, so the relationship between schizophrenic psychopathology and P300 amplitude appears to be, at least in part, trait-dependent. A reduced P300 amplitude may characterize a subgroup of schizophrenic patients with a disposition to cognitive disturbances and incomplete remissions.

Adult↗

Serotonergic ethanol effects and auditory evoked dipole activity in alcoholic and healthy subjects.

Ethanol has central serotonergic effects that may be of pathogenetic importance in a subgroup of alcohol-dependent patients with a central serotonergic hypofunction. Recent results indicate that pronounced amplitude increases of auditory evoked responses (tangential dipoles, N1/P2 component) with increasing stimulus intensity (loudness) may be an indicator of such a low serotonergic neurotransmission. Because of its serotonin-agonistic effects, ethanol can be expected to decrease this intensity dependence. Twenty-eight alcoholic patients were studied both in the intoxication phase and after 1 week of withdrawal. A reduced intensity dependence of the tangential dipole activity was observed in the intoxicated state. Correspondingly, a reduction of this parameter was found in 14 healthy subjects after an ethanol load (1 g/kg, p.o.).

Adult↗

Intensity dependence of auditory evoked potentials in behaving cats.

The intensity dependence of auditory evoked potentials (AEPs) recorded epidurally over the primary (AI) and secondary (AII) areas of the auditory cortex was studied in behaving cats during wakefulness, sleep and anesthesia. Four kHz tones of 50, 60, 70, and 80 dB SPL, presented in random order every 2 +/- 0.2 s by a bone conductor, elicited clear changes of the AEP amplitudes with increasing stimulus intensity, but individual components displayed different response curves. AEP components from the AI region showed saturation of their amplitude with stimulus intensity (P13, P34) or no amplitude increase (N19), while amplitude and intensity were linearly related in the AII area. The intensity dependence of the first positive component (P12/P13) was consistently stronger for the AEP recorded from the AI than from the AII area, while later components exhibited no difference between AI and AII. During slow wave sleep, the intensity dependence of this first positive component increased in the two areas, while that of later components decreased. Pentobarbital anesthesia abolished almost all later components and depressed the intensity dependence of the first positive component both in the AI and AII area. These results indicate that (I) clear intensity dependence of AEP exists in the cat auditory cortex and (2) this intensity dependence, especially that of the first positive AEP component, shares functional similarities to the human augmenting/reducing phenomenon in the auditory modality concerning regional differences and sleep-waking cycle.

Acoustic Stimulation↗

Reversible hepatotoxicity of paroxetine in a patient with major depression.

Selective serotonin reuptake inhibitors (SSRIs) are becoming widely used because of their favorable side-effect profile and their safety in overdose. We report about a patient with recurring major depression (DSM-IIIR) who was treated with paroxetine and developed a severe hepatotoxic reaction, which was reversed after withdrawal of the drug. Individual, patient-related causes for this side-effect were not found. To our knowledge, this is the first published case of a probably paroxetine-induced severe hepatotoxicity. Hepatotoxicity should be taken into account as a rare complication that may occur not only with tricyclic antidepressants (TCAs) but also with SSRIs.

Antidepressive Agents, Second-Generation↗

[Event related brain potentials as indicators of neurochemical dysfunctions in psychiatric patients].

The increasing knowledge concerning anatomical structures and cellular processes underlying event-related potentials (ERP) and methodological advances in ERP data analysis are beginning to bridge the gap between ERP and neurochemical aspects. ERP reflect directly postsynaptic effects of cortical neurotransmitters (e.g. GABA, glutamate) and indirectly modulating effects of neuromodulators (e.g. serotonin, acetylcholine) on cortical neuronal functioning and are therefore promising as noninvasive indicators of the functioning of neurochemical systems. Several recent reports are summarised suggesting that quite specific relationships may exist between certain ERP parameters and central cholinergic, noradrenergic and especially serotonergic function. Converging arguments from preclinical and clinical studies are presented supporting the hypothesis that the dependence of the response of primary auditory cortices on stimulus intensity (loudness) is regulated by the level of central serotonergic neurotransmission. This intensity dependence is shown to be of clinical value because, within different diagnostic categories, subgroups of patients with a serotonergic dysfunction can be identified and can be treated more specifically with serotonergic drugs.

Acetylcholine↗

Sensory cortical processing and the biological basis of personality.

Action-oriented personality traits such as sensation seeking, extraversion, and impulsivity have been related to a pronounced amplitude increase of auditory evoked scalp potentials with increasing stimulus intensity. Dipole source analysis represents a crucial methodological progress in this context, because overlapping subcomponents of the scalp potentials can be separated and can be related to their generating cortical structures. In a study on 40 healthy subjects, it was found that sensation seeking is clearly related to the auditory evoked response pattern (N1/P2-component, stimulus intensities: 60, 70, 80, 90, 100 dB SPL) of the superior temporal plane including primary auditory cortex, but not to that of secondary auditory areas in the lateral temporal cortex. These results support the concept that the serotonergic brain system, which is supposed to modulate sensory processing in primary auditory cortices, is an important factor underlying individual differences in sensation seeking.

Adult↗

The Tridimensional Personality Questionnaire and the intensity dependence of auditory evoked dipole source activity.

The relationship between the tridimensional personality questionnaire's (TPQ) dimensions "novelty seeking," "harm avoidance," and "reward dependence" and the intensity dependence of the auditory evoked N1/P2-component was investigated in healthy subjects. Using dipole source analysis, evoked activity of the primary auditory cortex (tangential dipole) could be analyzed at least in part separately from that of secondary auditory areas (radial dipole). It was found that the intensity dependence of the tangential dipole was positively correlated to the TPQ dimension "novelty seeking," but not to "harm avoidance" and "reward dependence." This is in line with findings concerning similar personality traits like "sensation seeking," "impulsivity," or "extraversion." It is therefore concluded that a strong intensity dependence may characterize subjects with an action-oriented and extroverted personality style. The results are discussed within the concept that a low central serotonergic neurotransmission is underlying both an impulsive personality type and a strong intensity dependence of the tangential dipole.

Adult↗

Antisocial tendencies and cortical sensory-evoked responses in alcoholism.

Alcohol-dependent patients with antisocial, aggressive, and impulsive behaviors form a subgroup, in which a dysfunction of the brain serotonin system is discussed as a pathogenetic factor. Early onset and a transmission from fathers to sons (type II alcoholism; Cloninger, 1987) are supposedly further characteristics of this subgroup. The response pattern of primary auditory cortices to auditory stimuli with different intensities is discussed as a noninvasive indicator of the level of central serotonergic neurotransmission. A strong intensity dependence of these responses is supposed to indicate low serotonergic neurotransmission and vice versa. A strong intensity dependence is therefore expected to characterize patients with antisocial tendencies. Auditory-evoked potentials (N1/P2 component) to stimuli in five different intensities were recorded in 53 hospitalized patients after 1 week of withdrawal. Dipole source analysis was performed to separate responses of primary and secondary auditory cortices. Patients with antisocial tendencies showed a significantly stronger intensity dependence of their evoked responses of primary auditory cortices (tangential dipoles). Age at onset and family history were not related to the intensity dependence of the evoked responses. The results support the notion that alcohol-dependent patients with strong intensity dependence and antisocial tendencies form a subgroup with a serotonergic hypofunction. These patients may respond favorably to a relapse prevention with serotonergic drugs.

Adult↗