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Biomedical subjects

U Hegerl

Publications and source records attributed to U Hegerl.

At least 19 recordsLinked to original sources

Event-related potentials. Do they reflect central serotonergic neurotransmission and do they predict clinical response to serotonin agonists?

The increasing knowledge concerning anatomical structures and cellular processes underlying event-related potentials (ERP) as well as methodological advances in ERP data analysis (e.g. dipole source analysis) begin to bridge the gap between ERP and neurochemical aspects. Reliable indicators of the serotonin system are urgently needed because of its role in pathophysiology and as target of pharmacotherapeutic interventions in psychiatric disorders. Converging arguments from preclinical and clinical studies support the hypothesis that the loudness dependence of the auditory evoked N1/P2-response (LDAEP) is regulated by the level of central serotonergic neurotransmission. Dipole source analysis represents an important methodological advance in this context, because the two N1/P2-subcomponents, generated by the primary and secondary auditory cortex known to be differentially innervated by serotonergic fibers, can be separated. A pronounced LDAEP of primary auditory cortices is supposed to reflect low central serotonergic neurotransmission, and vice versa. LDAEP is a parameter with potential clinical value since subgroups of patients with a serotonergic dysfunction can be identified and can be treated more specifically. In depressed patients, a significant relationship between strong LDAEP, indicating low serotonergic function, and a favorable response to SSRI has been found. Additionally, there is evidence from several studies with patients with affective disorders implicating a strong LDAEP as a predictor of favorable response to a preventive lithium treatment.

Arousal↗

Digitized analysis of abnormal hand-motor performance in schizophrenic patients.

Many studies have shown a high prevalence of discrete neuromotor disturbances in schizophrenic patients. It was hypothesized that these disturbances are lateralized and reflect a neurodevelopmental disorder underlying schizophrenia. A new method for assessing subtle motor dysfunction and hemispheric asymmetries is the registration of hand movements with a digitizing tablet. Using this method, we studied hand-motor dysfunction and its lateralization in schizophrenics, as compared with healthy controls. All subjects (27 schizophrenic patients, 13 of them without neuroleptic medication, the others under neuroleptics; 31 healthy controls) drew super-imposed concentric circles. We computed kinematic parameters reflecting velocity and automatization to quantify neurological soft signs (NSS). The patients had significant impairments of regularity of repetitive hand movements, as compared with the healthy controls (F> or =5.35; p< or =0.024(*)). Comparing differences of left- and right-hand performance between patients and controls, we found longer stroke duration (F=(15,98); p=0.000***) and decreased automatization (F=18,14; p=0.000***), especially on the left side in schizophrenic patients. Measuring hand movements with a digitizing tablet is a sensitive method for assessing subtle motor dysfunction in schizophrenic patients, not reflected in the scores of clinical scales. Our findings show NSS in schizophrenic patients, independently of neuroleptics. Further, the hypothesis of lateralization of cerebral structures generating NSS towards the right hemisphere in schizophrenia is supported.

Adult↗

Loudness dependence of auditory evoked potentials in obsessive-compulsive disorder: a pilot study.

In recent years it has been suggested that a serotonergic dysfunction is involved in the pathogenesis of obsessive-compulsive disorder (OCD). The loudness dependence of auditory evoked potentials (AEPs) is one of the best validated indicators of the activity of the serotonin system in humans. To explore the validity of the hypothesis of a serotonergic dysfunction in OCD, the loudness dependence of AEPs of 22 medication-free OCD patients were compared with those of 22 age- and gender-matched healthy subjects. Auditory evoked N1/P2 activity to tones of increasing intensity was studied using dipole source analysis. Contrary to the hypothesis, OCD patients and healthy controls did not differ in their LDAEPs of the tangential dipole in particular, located in the primary auditory cortex and closely related to central serotonergic activity. Furthermore, no significant correlation was found between the severity of obsessive-compulsive or depressive symptoms and the loudness dependence of AEPs. These findings do not support the hypothesis of a serotonergic dysfunction in OCD patients.

Adult↗

[Pharmacotherapy of depression in the elderly].

Antidepressants are not only effective in younger adults but also in older persons with depression. However there are peculiarities, which have to be taken into account when treating older patients. The enhanced risk of side effects has to be balanced with the more serious consequences of an untreated depression in old age. The efficacy in older patients has been proven not only for tricyclic antidepressants but also for SSRI and other newer antidepressants. The easy handling, the side effect profile and the safety in overdose are advantages of SSRI and newer antidepressants, which become particularly important in old age. The advantages and disadvantages of different classes of antidepressants with regard to comorbidity and comedication are discussed. In older subjects, changes of dosage should be slower and for some, but not for all antidepressants, dosage should be lower.

Adult↗

[The state of psychiatry in Ukraine. Psychiatric hospitals in Kiev and Shitomir].

The situation of psychiatric patients in the Ukraine is determined by the financial and economic difficulties of this country. In the larger cities, so-called polyclinics take care of ambulant psychiatric patients. However, no other social psychiatric institutions exist. Here, the modalities of hospital psychiatric treatment are discussed using the psychiatric hospitals in Kiev and Shitomir as examples. Undertreatment is also a problem, because only a few psychopharmacological drugs are produced in the Ukraine. Import of new psychopharmacological agents is hampered by economical problems. Improving the availability of psychopharmacological drugs and the establishment of a social psychiatric network are major aims for psychiatrists working in Ukraine.

Commitment of Persons with Psychiatric Disorders↗

The loudness dependency of the auditory evoked N1/P2-component as a predictor of the acute SSRI response in depression.

RATIONALE: A serotonergic dysfunction is supposed to play a pathogenetic role in depression, but there is a considerable number of non-responders in the acute treatment of depression with serotonergic agents like SSRI. Thus, an indicator of central serotonergic activity could lead to a more specific pharmacological treatment of depression. In animal and human data there is a growing amount of evidence that a strong loudness dependency of late auditory evoked potentials (LDAEP) is an indicator of low serotonergic activity and vice versa. OBJECTIVE: In 29 depressive inpatients (DSM-III-R diagnosis 296.x in 28 patients, 300.4 in one patient), the hypothesis was tested that a strong LDAEP prior to treatment can predict a better clinical outcome under SSRI treatment over 4 weeks. RESULTS: Patients with a strong pre-treatment LDAEP had a significantly greater decrease of depressive symptoms (Hamilton Scale for Depression) after 4 weeks than patients with a flat LDAEP. Significantly more responders fell into the group with a high LDAEP. Contrary to what might be expected, a second recording in a subsample of 19 patients after 4 weeks of treatment failed to show changes in the LDAEP. CONCLUSION: Our finding confirms the hypothesis that a strong LDAEP, indicating a low serotonergic activity, is related to a favorable response to acute SSRI treatment in depression. The LDAEP is a promising tool for the prediction of response to serotonin agonists in depression and it seems to be of clinical importance.

Acoustic Stimulation↗

Dipole localization of P300 and normal aging.

At present, our understanding of how normal aging affects in vivo brain function is rudimentary. Therefore, the aim of the present study was to investigate age effects on auditory P300 topography. A recently developed dipole source model for P300 distinguishes overlapping P300 subcomponents and enhances reliability as well as validity of the measurement. 67 healthy subjects were examined using the P300 dipole model in addition to the scalp data measurement. The results show that P300 subcomponents reflect functionally different processes concerning age changes of P300 activities. Temporo-parietal P300 is smaller in older subjects, whereas frontal P300 is not attenuated. Age affected both P300 subcomponents' latencies. Therefore, the functionally different alteration of P300 subcomponents might be the reason for P300 topography changes with the P300 maximum more frontally in older age.

Acoustic Stimulation↗

[Digitized analysis of hand movements in psychiatry. Methods, clinical findings and perspectives].

Numerous morbo- and pharmacogenic motor disorders are signs of psychiatric disease. In past, their exact and quantitative registration has not been possible or only possible using quite extensive procedures. Now we can use newer methods like the computer-aided analysis of hand movements, an elegant procedure allowing the detailed representation of discrete motor dysfunction. While these procedures are used with increasing tendency in neurology, their use aiming the investigation of psychiatric hypotheses is still at the beginning. Relevant application fields of the computer-aided analysis of hand movement are the differentiated and quantitative registration of movement disorders that could only be detected by use of rating scales so far; the registration of subclinical motor abnormalities leading to the detection of the participation of the motor system in certain subgroups of psychiatric patients; the differentiation of morbo- and pharmacogenic motor disorders (e.g. hypokinesia induced by neuroleptics versus schizophrenic negative symptomatology); the registration of neurological soft signs (e.g. in schizophrenic patients); the individual dose adjustment accounting for the threshold of extrapyramidal motor side effects (EPMS) under neuroleptic treatment and the detection and documentation of clinical and subclinical tremor. For some of these application fields there already exist promising findings. Some newer results will be presented. Schizophrenic patients were found to manifest impairments of velocity and degree of automatization and a reduced regularity of repetitive hand movements (fine motor dysdiadochokinesia)--a possible indicator for a disturbance of cerebral development. Patients with Alzheimer's disease showed loss of automatization and well preserved peak velocity. This finding could be relevant for the early detection of Alzheimer's dementia. Distal EPMS induced by neuroleptics can be exactly documented and their course can be represented using this method. The quick and economical utilization of digitized analysis of hand movements makes this procedure suitable for a broader application in the ambulatory setting.

Hand↗

Platelet monoamine oxidase activity in alcoholics with and without a family history of alcoholism.

A number of studies point at platelet monoamine oxidase (MAO) activity being reduced in alcoholics with a family history of drinking, this being a possible vulnerability marker for alcoholism. To test this hypothesis, we examined a group of recently detoxified alcoholics with high (n = 25) and low genetic loading for alcoholism (n = 28) and a group of healthy controls (n = 21). Clinical assessments were made using the SCID II interview for psychiatric disorders, the Family History Assessment Module and the Semi-Structural Assessment of Genetics in Alcoholism, a questionnaire especially designed for genetic studies. Platelet MAO activity with and without ethanol stimulation and the percentage of MAO activity with ethanol did not differ between groups. The only significant difference was a lower inhibition of MAO activity with ethanol in alcoholics both with and without a family history compared to controls. In patients with antisocial personality traits, platelet MAO activity was also not found to be different from other alcoholics. Our findings question the hypothesis of reduced platelet MAO activity to be a possible vulnerability marker for alcoholism.

Adult↗

Lithium-induced EEG changes in patients with affective disorders.

In 12 patients with affective disorders (ICD-10: F31, F32, F33), EEGs were recorded before and after 4.4 months of lithium treatment. Effects of lithium on the EEG were analyzed by power spectral analysis controlled for vigilance. We found (1) an increase in relative power in both delta and theta band which was related to the lithium plasma level, (2) a decrease in relative alpha power especially at occipital leads and (3) a reduction of the dominant alpha frequency. The changes in relative power were more pronounced in the right hemisphere, which is in contrast to the hypothesis of a site-specific localization of lithium effects only in left anterior regions.

Aged↗

Periodic motor impairments in a case of 48-hour bipolar ultrarapid cycling before and under treatment with valproate.

Motor impairments of psychiatric patients can be assessed with digital recordings of handwriting tasks. The investigation of patients with bipolar affective disorders differentiates intraindividual changes related to the patient's fluctuating affective states. An unmedicated 67-year-old male with 48-hour bipolar ultrarapid cycling was investigated during 8 consecutive days of ultrarapid cycling and 4 weeks later, after remission under treatment with valproate. The handwriting skills of the patient followed the same rhythmic changes of the psychopathology in the first part of the study and a steady pattern in the second phase, after remission. Therefore, it can be assumed that the handwriting skills reflect a state marker of the disease. Poorer handwriting skills on the manic days, as compared to the depressive ones, support the hypothesis of a low arousal in manic patients.

Aged↗

Adhesio interthalamica in male patients with schizophrenia.

OBJECTIVE: The authors investigated whether absence of the adhesio interthalamica in patients with schizophrenia constitutes a marker of early developmental neuropathological changes. METHOD: Thirty male patients with schizophrenia and 30 healthy male subjects were recruited for study. Magnetic resonance imaging was performed, and the presence or absence of the adhesio interthalamica was determined for each subject. The length and volume of the third ventricle were also measured. RESULTS: No differences in the presence or absence of the adhesio interthalamica were found between patients with schizophrenia and normal comparison subjects. Patients without the adhesio interthalamica had significantly higher scores for negative symptoms than patients with the adhesio interthalamica. There was no correlation between absence of the adhesio interthalamica and length and volume of the third ventricle in either patients or comparison subjects. CONCLUSIONS: The findings suggest that patients with schizophrenia who do not have the adhesio interthalamica are characterized by more severe negative symptoms.

Adolescent↗

Clinical and biological findings in a case with 48-hour bipolar ultrarapid cycling before and during valproate treatment.

BACKGROUND: The rare cases of patients with 48-hour ultrarapid cycling allow close investigation of mood cycles in affective disorders, because rhythmic changes in psychopathologic state and biological parameters happen very precisely. METHOD: A 67-year-old white man who had experienced bipolar 48-hour ultrarapid cycling (DSM-IV 296.80) for several years was studied without any medication and then again studied 4 weeks later during treatment with valproate (1800 mg/day). RESULTS: Objective and self ratings revealed pronounced manic states 1 day and depressed states the following day, which were found to be accompanied by rhythmic fluctuations in behavior and electroencephalographic parameters, blood cortisol and growth hormone levels (both elevated on depressive days), and urinary metanephrine (dopamine metabolite) and norepinephrine levels (both elevated on manic days). Using single photon emission computed tomography, regional blood flow in the left thalamus was lower than in the right thalamus on the manic day, while symmetric perfusion of the thalamus was found on the depressive day. Under valproate treatment, the patient remitted completely, and significant rhythmic changes in most of the biological parameters were no longer detectable. CONCLUSION: The biological findings in this patient with bipolar 48-hour ultrarapid cycling, which correspond to those in other types of affective disorders, suggest that disturbances in the diencephalon-pituitary axis may be especially correlated to pathologic changes of mood.

Aged↗

[The Japanese version of the serotonin syndrome scale (JSSS)].

The serotonin(5-HT) syndrome(SS) is a condition of both the central and peripheral 5-HTergic hyperstimulation, characterized by a constellation of 5-HT-related side effects(confusion, agitation, restlessness, myoclonus, hyperreflexia, diaphoresis, shivering or tremor in the setting of the recent addition of 5-HTergic agents. The SS is produced most often by the concurrent use of monoamine oxidase inhibitors and other 5-HTergic agents. However, more recent reports suggest that the tricyclic antidepressant or selective serotonin reuptake inhibitor(SSRI) monotherapy induces the SS. Recently, for the operationalized assessment of both the presence and the severity of the core symptoms of the SS, Hegerl et al. developed the Serotonin Syndrome Scale(SSS) as a modification of the diagnostic criteria of the SS proposed by Sternbach. Since, in Japan, some novel 5-HTergic agents have been, and will be in use, recognition of the SS is quite important. Therefore, for clinical application of SSS, we prepared the Japanese-language version (JSSS).

Diagnostic Techniques, Neurological↗

Is the EEG helpful in diagnosing and monitoring lithium intoxication? A case report and review of the literature.

Lithium is potentially toxic to the central nervous system. Clinical lithium neurotoxicity may appear at any time during therapy and may go unrecognized. Failure to appreciate this fact leads to delays in diagnosis and treatment, placing the patient at risk of permanent neurological damage or death. In spite of a largely clinical diagnosis of lithium intoxication, the EEG provides an objective criterion of intoxication. We report a case of lithium intoxication with neurotoxic symptoms associated with marked EEG changes despite moderate lithium serum levels. In contrast to the interindividually varying EEG changes under uncomplicated lithium therapy, pathological EEG findings are the rule in the case of intoxication. Several reports evince a closer relationship between neurotoxic symptoms with EEG changes than with serum levels of lithium. This is of clinical interest with respect to intoxication under therapeutic lithium serum levels, since the EEG is the only examination indicating an intoxication. In patients with intoxication, the phenomenon of long-lasting EEG changes after discontinuation of lithium is discussed with respect to neuronal storing of lithium and persisting neurological disturbances.

Aged↗

[Depression and suicidal behavior more effectively controlled by a team approach. Pilot project to optimize diagnosis and therapy].

The aim of the competition (Specialist-field Networks in Medicine "MedNet") announced by the Federal Ministry for Education and Research (BMBF) is to stimulate the creation of supraregional networks for specific diseases, in order, in this way, to improve cooperation and the transfer of knowledge between research institutions and various levels of medical care. The MedNet "Depression, Suicidal tendency" is one of the winners of this BMBF competition". In view of the central role played by the family doctor in the care given to patients with depressive disorders, permanent improvement in cooperation between physicians in private practice and the research institutions is a central aspect of the planned MedNet activities.

Depressive Disorder↗