Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol.

RATIONALE: Flupentixol (FLX) has been used as a neuroleptic for nearly 4 decades. In vitro data show comparable affinity to dopamine D(2), D(1) and 5-HT(2A) receptors and recently, FLX showed to be not inferior to risperidone in schizophrenic patients with predominant negative symptomatology, which was implicated with flupentixol's interaction with 5-HT(2A) and/or D(1) receptors. OBJECTIVES: To assess in vivo receptor occupancy (RO) in patients clinically treated with FLX (n = 13, 5.7 +/- 1.4 mg/day) in comparison with risperidone (RIS, n = 11, 3.6 +/- 1.3 mg/day) and haloperidol (HAL, n = 11, 8.5 +/- 5.5 mg/day). MATERIALS AND METHODS: Each patient underwent two PET scans with 3-N-[(11)C]methylspiperone (target: frontal 5-HT(2A)), [(11)C]SCH23390 (striatal D(1)) or [(11)C]raclopride (striatal D(2)). RO was calculated as the percentage reduction of specific binding in comparison with healthy controls. RESULTS: D(2)-RO under FLX was between 50% and 70%, indicating an ED(50) of about 0.7 ng/ml serum. 5-HT(2A) and D(1)-RO was 20 +/- 10% and 20 +/- 5% (mean, SEM). Under HAL, D(1)-RO was 14 +/- 6% and under RIS not significantly different from zero. CONCLUSIONS: We were able to demonstrate a moderate 5-HT(2A) and D(1) occupancy under clinically relevant doses of flupentixol, albeit lower than expected from in vitro data and clearly below saturation. Therefore, if flupentixol's efficacy on negative symptoms is based on its interaction with 5-HT(2A) and/or D(1) receptors, it should be highly dependent on serum concentration and thus on dosage and metabolism. However, these data suggest that mechanisms other than D(1) or 5-HT(2A) antagonism may contribute to flupentixol's efficacy on negative symptoms.

[A pilot project with clowns in psychiatric clinics]. / Clowns in der Psychiatrie? Ein Pilotprojekt.

BACKGROUND: This project examines whether visits of specially trained clinic clowns, as established in pediatrics, would also be useful in psychiatry. METHODS: We describe the effects of a 6-week phase with one clown visit per week in a ward for acutely ill geriatric patients. The patients and medical team were also questioned about their attitudes towards the clowns. RESULTS: We found more positive attitudes in patients after this phase. CONCLUSIONS: We interpret this result as an indication of positive effects and sufficient reason to initiate similar projects in the future.

CADASIL: underdiagnosed in psychiatric patients?

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is exclusively related to symptoms of the central nervous system. Retrospectively in up to 15% the initial presentation is psychiatric disturbances. In these cases the diagnosis often is delayed or missed. METHOD: Two cases of CADASIL diagnosed in a psychiatric hospital are presented. RESULTS: Both patients were admitted to the gerontopsychiatric department (one because of a suicidal attempt and a depressive episode, the other because of cognitive decline and progressive personal neglect). Brain magnetic resonance imaging (MRI) showed severe leukoencephalopathy in the absence of cardiovascular risk factors. In both cases, diagnosis of CADASIL was made by the identification of specific granular osmiophilic material in skin biopsies. CONCLUSION: Brain MRI should be performed in all cases of late onset of severe psychiatric symptoms. CADASIL should be considered as a possible differential diagnosis whenever a marked leukoencephalopathy is detectable. Diagnosis can be verified by taking a skin biopsy or by specific genetic testing.

Diminished production of proinflammatory cytokines in patients with Alzheimer's disease.

Cerebral inflammation as well as systemic immunological alterations have been reported in Alzheimer's disease (AD). We examined the production of the proinflammatory cytokines interleukin-6, interleukin-12, interferon-gamma, and tumor necrosis factor-alpha in whole blood cell cultures of AD patients and age-matched controls. The production of all measured cytokines after mitogen stimulation is significantly decreased in the AD group compared to controls. The results reflect an attenuated secretory activity of monocytes/macrophages, but also of T-helper cells. The data sustain the assumption that a systemic, possibly age-related alteration of immune mechanisms may play a pathogenetic role in the development of AD.

[Depression in Hashimoto's encephalopathy. Successful treatment of a severe depressive episode with a glucocorticoid as an add-on therapy]. / Depression bei Hashimoto-Enzephalopathie. Erfolgreiche Behandlung einer schweren depressiven Episode mit einem Kortikosteroid als Add-on-Therapie.

Characteristic clinical findings of Hashimoto's encephalopathy (HE) are stroke-like episodes, epileptic seizures, myoclonus, psychosis, and progressive cognitive impairment. Diagnosis of HE is supported by elevated antithyroid antibodies, an abnormal EEG, and by good response to steroids. We report on a 74-year-old female patient with a severe depressive episode who showed no treatment response to citalopram 40 mg/day and venlafaxine 150 mg/day. Diagnostic examination revealed an abnormal EEG, elevated thyroid peroxidase antibodies (TPO-Ab), and older postinflammatory changes in thyroidal sonography. We diagnosed a depression in HE and began treatment with prednisolone 70 mg/day with stepwise dose reduction, continuing treatment with venlafaxine 150 mg/day. Within 4 weeks of treatment, the severe depressive episode disappeared as well as abnormal EEG. In addition, serum values of TPO-Ab decreased. In HE, depressive symptoms can possibly be seen in a subgroup of patients or in the early course of the disease. Diagnosis of HE should be included in diagnostic procedures in cases of therapy-refractory depression because of a good response of HE to steroids.

[Dementia as a primary symptom in late onset multiple sclerosis. Case series and review of the literature]. / Demenz als Erstsymptom bei spät beginnender Multipler Sklerose. Fallserie mit Literaturübersicht.

Cognitive impairment is meanwhile accepted as a well-known symptomatology affecting up to 60% of the patients even in the early disease course of multiple sclerosis (MS). After a longer duration the development of dementia is not unusual. However, cognitive dysfunction as the primary or only manifestation of MS is thought to be rare. We report on four elderly patients referred to the memory clinic of our psychiatric university hospital because of beginning dementia. All of them were found to have evidence of a chronic inflammatory CNS process compatible with the diagnosis of MS. At the beginning of their symptomatology all patients were older than 60 years . Just in one case, progressive gait disturbances beginning after cognitive decline contributed to restriction in the activities of daily living. Data of 239 cases of the literature were reviewed and revealed motor disturbances as the main initial symptom and often a primary progressive course with unfavourable prognosis in late onset MS. Until now dementia as the primary symptomatology has not been described in patients older than 60 years. Possibly MS as a differential diagnosis in dementia as well as cognitive impairment as an initial symptom of MS is under-recognized.

[Alzheimer's disease with secondary Parkinson's syndrome. Case report of a patient with dementia and Parkinson's syndrome after long-term occupational exposure to insecticides, herbicides, and pesticides]. / Präsenile Demenz vom Alzheimer-Typ mit sekundärem Parkinson-Syndrom. Falldarstellung eines Patienten mit Demenz und Parkinson-Syndrom nach jahrelanger nebenberuflicher Insektizid-, Herbizid- und Pestizidexposition.

This case report describes long-term occupational exposure to agricultural insecticides, herbicides, and pesticides as possible environmental risk factors of Alzheimer's disease (AD) and Parkinson's syndrome in a 59-year-old man. Initially the patient complained about disturbances in concentration, mnestic deficits, and problems finding words. In the further course of the disease, he developed Parkinson's syndrome with predominant hypokinesia and rigor in addition to mild-to-moderate dementia. Low levels of beta-amyloid 1-42 were found in the CSF. Electroencephalography showed left frontotemporal theta waves. Cranial MRI revealed general brain atrophy with a maximum biparietally. In cerebral positron emission tomography, general hypometabolism was found with maxima biparietally and left frontally. The possible differential diagnosis of AD and Parkinson's syndrome is discussed.

[Correlation of diffusion-weighted magnetic resonance imaging with neurological deficits in sporadic Creutzfeldt-Jakob Disease]. / Korrelation von diffusionsgewichtetem MRI und neurologischer Symptomatik bei der sporadischen Form der Creutzfeldt-Jakob-Krankheit.

This case report describes the sporadic Creutzfeldt-Jakob disease (CJD) of a 53-year-old man who initially complained about vertigo and dizziness. Within 18 weeks, he developed impaired memory, hemineglect, and sensory impairment of the left half of the body. A CSF tap was positive for 14-3-3 protein and showed increased tau protein, neuron-specific enolase (NSE), and the astroglial protein S-100 B. The EEG showed right temporal sharp waves without periodicity. Diffusion-weighted MRI revealed hyperintensities in the right temporo-occipital cortex which corresponded well with hypometabolic areas in a PET scan and the neurological and neuropsychological deficits. The morphological FLAIR T2 MRI showed no pathological changes. Within 20 weeks, the patient developed severe dementia with decreased spatial orientation and myoclonia, became incontinent, and was confined to bed. He died within 22 weeks after the first presentation of symptoms.

[Effects of autogenic training in elderly patients]. / Effekte von Autogenem Training bei Alteren.

Autogenic training (AT) is a widely available relaxation method with beneficial outcome on physiological and psychological functioning. In our study, we wanted to test the effects of an AT course in cognitively impaired, frail elderly. After a 3 month waiting period (control), AT courses (intervention) of 3 months duration were offered in 2 nursing homes. Thirty-two frail elderly took part in the study, 24 of them had a psychiatric diagnosis (mean age 82.1 +/- 7.2 years, CAMCOG 75.5 +/- 15.7, MMSE 23.3 +/- 4.3, HAMD 10.0 +/- 3.6, NOSGER 57.2 +/- 18.4, AT-SYM 32.9 +/- 17.6 points). Eight participants dropped out during the waiting period, 8 during the course. From the 16 participants, 15 (94%) were able to learn the AT according to subjective, 9 (54%) according to objective criteria. The ability to practice the AT successfully correlated with the CAMCOG (p = 0.001) and the NOSGER (p = 0.01) score. Participants with a dementia syndrome had major difficulties, whereas age, depressiveness, and number of complaints (AT-SYM) had no influence on the ability to learn the AT. There was no intervention effect, measured with the HAMD, NOSGER, AT-SYM and MMSE. In the pre-post comparison of training sessions, a significant improvement in general well being was found (p < 0.001). Mentally impaired, frail elderly participants are able to learn the AT. Cognitive impairment is disadvantageous for a successful participation.

[Treatment courses and therapeutic effectiveness of a psychogeriatric day hospital]. / Behandlungsverläufe und therapeutische Effektivität in einer gerontopsychiatrischen Tagesklinik.

Since 1976, 37 psychogeriatric day hospitals have been set up in Germany. As only few empirical studies on the effectiveness of this day hospital system are available even 25 years on, the treatment course of 58 patients attending the psychogeriatric day hospital run by the Department of Psychiatry, University of Tübingen was evaluated. The course analysis was based on a series of tests comprising the following questionnaires: Social Situation Scale, Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Munich Quality of Life Dimension List (MLDL), Mini Mental Status (MMS), Hamilton Depression Scale, and Cumulative Illness Rating Scale (CIRS). Women accounted for three-quarters of the sample, and men for one-quarter. The average age was 72 years. The fact that only 16% of the patients had been transferred from psychiatric hospitals and that more than half had been referred directly by their local doctors underlines the acute-psychiatric nature of the institution. More than 80% of the patients were discharged to their previous place of residence. A highly significant improvement in affective state was verified by the Hamilton Depression Scale. Significant improvements were also registered in the following items: general satisfaction with life, state of health, physical and mental performance, and scope for personal development. The quality of life, measured with the Munich Quality of Life Dimension List (MLDL), improved in nine of the nineteen items covered, with correction of the significance level alpha taken into account. The treatment outcomes confirmed the therapeutic effectiveness of this type of psychogeriatric institution from aspects of acute psychiatry too and should encourage the continued expansion of partial hospitalization facilities for the elderly.

A case of paranoia with severe consequences. From a historical approach to a multidimensional understanding of chronic delusional disorder.

Following a brief resume of the history of the notion of paranoia, we present the case history of a 67-year-old female patient, who suffered from irreversible physical handicap as a result of chronic delusion. Against the background of the on-going controversy about the existence of paranoia as a distinct illness, we discuss the contemporary understanding of delusional disorders, emphasising the importance of a multidimensional therapeutic approach.

Dynamic regulation of EEG power and coherence is lost early and globally in probable DAT.

Electroencephalographic (EEG) findings in dementia of Alzheimer type (DAT) include slowing of alpha frequency, loss of alpha band power, increased theta and delta power and reduced coherence. Here it is evaluated whether a) EEG acquisition during different functional states facilitates the detection of DAT-associated EEG changes, and b) EEG changes in mild DAT are topographically confined or global. Power spectra and coherence of EEGs from 29 patients with mild probable DAT and 28 age- and sex-matched controls were compared during three cognitive states. Group differences in power spectra and coherence were largest during resting with eyes open, yielding a 77% correct classification result. Already in early stages of probable DAT, EEG changes were topographically wide-spread. The task-related up- and down-regulation of power and coherence was impaired already in mild probable DAT. We propose to augment clinical EEG assessment by including a quantitative analysis of the dynamic power and coherence changes from rest, eyes closed to eyes open in suspected DAT.

[Video technology--a medium for milieu therapy?]. / Video--Ein milieutherapeutisches Medium?

Video technology has been in use in the psychiatric field for more than 20 years for diagnostic, scientific, co-therapeutic or educational purposes. However, little is known of its potential applications and impact as an instrument in psychotherapy or environmental therapy. For this reason a new cinematographic project applying widespread video technology in environmental therapy, too, has been launched. All patients at our psychiatric hospital are involved in film selection, can cooperate at different organizational levels, and have regular opportunities to see films. The technical, the organizational and, in particular, the legal preconditions are set out, followed by a report on experience gained in use of video films within the setting of a psychiatric hospital. Reference is also made to economic aspects, therapeutic effects and contraindications.

Therapeutic options in Charles Bonnet syndrome.

The term 'Charles Bonnet syndrome' refers to visual pseudohallucinations occurring especially in elderly people with reduced visual acuity. Despite numerous case reports, few successful methods of treatment have been described. Therapies with classical neuroleptics, antidepressants or benzodiazepines have generally been found to be unpromising. Only with carbamazepine treatment has improvement been observed in a few cases. In the three cases reported here, we successfully treated the condition with the atypical neuroleptic melperone.

Alois Alzheimer (1864-1915)--student days and first scientific activities.

This article gives an overview of Alois Alzheimer's years as a medical student, his most influential teachers, and the origin of his interest in (neuro)histopathology. The neuron theory discussions of that time are reviewed briefly.

[Changes in the structure of an Alzheimer family group]. / Strukturwandel einer Alzheimer-Angehörigengruppe.

The family of Alzheimer patients is in general deeply engaged in caring for the patient and is faced by enormous physical and psychological stress. Today in Germany there are more than 100 groups of family members caring for Alzheimer patients. These groups are either headed by an expert, layman, or supported by experts. The Tübingen Alzheimer group has gone through all three stages since its foundation in 1991. Experience gathered with these different forms of organisation are reported.

[Use of supportive autogenic training in multiple morbidity in geriatric psychiatry patients]. / Der Einsatz von supportivem autogenem Training bei multimorbiden, gerontopsychiatrischen Patienten.

23 multimorbid, geronto-psychiatric patients, aged 60 years or older, participated in a "supportive" course of autogenic training according to Schultz. Participating in the course an average of 7 +/- 3 weeks, 17 (76%) of the subjects were able to learn the training. In general, subjects reported a better general condition after the training sessions, measured with visual analogue scales (p < 0.001). The psychopathological status improved significantly during the time of the course (BPRS: p < 0.001; GDS: p < 0.001). No significant change was found in the cognitive state (MMSE) and the statements on the "list of complaints" ("Beschwerdenliste"). The global training success was better in the psychopathological less affected than in the more severely ill (BPRS prior r = 0.64, p = 0.001, GDS prior r = 0.46, p < 0.05). No correlation was found between training success and age, number of somatic diseases, number of medication, MMSE and the "Beschwerdenliste". Autogenic training is a useful component in psychotherapeutic and psychiatric therapy for elderly multimorbid in- and outpatients. A half-open group, two therapy sessions per week, reciting the training formulae aloud, a structured, simple setting and co-therapists proved to be worthwhile.