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Biomedical subjects

H M Emrich

Publications and source records attributed to H M Emrich.

At least 55 records · Page 3Linked to original sources

Dopamine transporter binding in Gilles de la Tourette syndrome.

Preliminary studies in patients with Gilles de la Tourette syndrome (TS) provided evidence of presynaptic dopaminergic dysfunction, demonstrating increased reuptake sites. Therefore we investigated striatal dopamine transporter binding in 12 TS patients and 9 control subjects using single photon emission computed tomography and 123I-labeled 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane. In TS patients we found significantly higher relative striatal activity ratios (mean +/- SD 12.33 +/- 3.58) than in controls (9.36 +/- 1.35, P< 0.05). Only five patients, however, showed striatum/occipital cortex ratios more than 2 SD above the normal means. Seven patients had activity ratios within the average ratio of the control group plus 2 SD. Regarding the relationship between clinical parameters and striatum/occipital cortex ratios, we found an association between binding ratios and "self-injurious behavior" and "lack of impulse control." This study corroborates previous data suggesting an involvement of the dopaminergic system in TS pathology. Our results demonstrate that an increase in dopamine transporter capacity is a possible but not a necessary alteration, and which appears more likely when self-injurious behavior and lack of impulse control are associated.

Adult↗

[Detoxification of poly-substance abusers with buprenorphine. Effects on affect, anxiety, and withdrawal symptoms].

We used an open-labeled, 21-day inpatient detoxification treatment to compare the short-term effects of a 10-day buprenorphine plus 19-day carbamazepine regimen (n = 15) to a 14-day oxazepam plus 19-day carbamazepine regimen (n = 12) during rapid detoxification from opioids and other abused drugs. Somatic and psychopathological changes were assessed using the following rating scales: ASI, HAMD, SCL-90-R, and SOWS. Eighteen of 27 patients (67%) completed the study. Four dropouts (27%) were treated with buprenorphine/carbamazepine (BPN/CBZ) and the other five dropouts (42%) were treated with oxazepam/carbamazepine (OXA/CBZ). Repeated measures analysis of variance showed that SOWS scores were significantly less pronounced with BPN-CBZ than with OXA/CBZ. On the first day of admission, no significant difference in HAMD scores was detected (BPN/CBZ 11.6, BPN/CBZ 1.0). On day 14, HAMD was significantly less pronounced in BPN/CBZ (3.0) than in OXA/CBZ (6.1). BPN/CBZ showed a significant improvement in the ASI score on days 7 and 14 compared with OXA/CBZ. Three of nine items of the SCL-90-R showed a trend toward less pronounced outcome in BPN-CBZ. No severe side effects occurred during treatment in either group. The buprenorphine/carbamazepine regimen provided significantly more effective relief from affect disturbances and withdrawal syndromes than the oxazepam/carbamazepine regimen. The pharmacological basis of these effects of buprenorphine (kappa-antagonism activity,mu-agonism activity) are discussed.

Adult↗

Different effects of nabilone and cannabidiol on binocular depth inversion in Man.

The physiological and pathophysiological roles of the central nervous endogenous cannabinoid system are not completely understood, but still represent a challenge in basic neurobiological, cognitive, and psychiatric research. The system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, provides a model of impaired perception during psychotic states. Using this model the effects of nabilone, a psychoactive synthetic 9-trans-ketocannabinoid, and of cannabidiol, the main natural component of herbal cannabis, and a combined application of both substances on binocular depth inversion and behavioural states were investigated in nine healthy male volunteers. The time course of the effects of both substances on binocular depth inversion was analysed after oral administration using three different groups of natural stimuli. A significant impairment of binocular depth perception was found when nabilone was administered, but combined application with cannabidiol revealed somewhat reduced effects on binocular depth inversion. The influence of psychoactive cannabinoids on this perceptual model and the role of the endogenous cannabinoid system in visual information processing are discussed.

Adult↗

Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial.

OBJECTIVE: Originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological eftfects on the central nervous system. In addition. only a few studies reported on certain antidepressive properties of amantadine. This effect was highlighted by the discovery of its antiviral effect on Borna disease virus (BDV), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. Therefore, the therapeutical use of amantadine in BDV-infected depressive patients was investigated. METHODS: In this open trial, amantadine was added to antidepressive and or mood-stabilizing compounds treating BDV-infected depressed patients (n = 25) with bipolar or major depressive disorders. Amantadine was given twice a day (100-300 mg/day) for a mean of 11 weeks. Antidepressive treatment response was measured on the Hamilton rating scale for depression (HAM-D) and/or with an operationalized diagnostic criteria system (OPCRIT: version 3.31). Virological response was measured by expression of BDV infection parameters in blood samples. RESULTS: The overall response rate of the amantadine augmentation in the BDV-infected patients with regard to depressive symptoms was 68% after a mean of 2.9 weeks of treatment. Bipolar I patients improved faster and did not show any following hypomania. In addition, the decrease of depression tended to correspond with the decrease in viral activity. CONCLUSION: Amantadine appears to show a remarkable antidepressive efficacy in BDV-infected depressive patients. The antidepressive effect in this open trial appeared to be comparable to standard antidepressives, possibly being a result of its antiviral effect against BDV as a potentially relevant etiopathogenetic factor in these disorders.

Adult↗

Dopamine D2 receptor imaging in Gilles de la Tourette syndrome.

OBJECTIVES: To examine postsynaptic dopamine D2 receptors in Tourette syndrome (TS). MATERIAL AND METHODS: Seventeen patients and a control group were investigated using single photon emission computed tomography (SPECT) and iodobenzamide (123I-IBZM). RESULTS: In neuroleptic treated patients (n = 7) 123I-IBZM-binding was significantly reduced compared to both normal controls (P < 0.0001) and unmedicated patients (P < 0.001). In unmedicated patients (n = 10) mean binding ratio did not differ from that of control group. Patients in advanced stages of the disease, however, revealed significantly reduced relative striatal binding compared to patients in the early stages (P<0.005) and normal controls (P<0.0001). CONCLUSION: The results lend further support to the hypothesis that the dopamine receptor is involved in TS pathology. During the natural course of the disease tics often improve in early adulthood. It is suggested that this spontaneous recovery from tics may be associated with reduced receptor binding capacity.

Adolescent↗

[Remembering, forgetting and depression. Time-conceptual implications of affective disorders].

As a consequence of reflections about the relevance of remembering and forgetting in psychiatric disorders, aspects of the psychopathology of the dimension of time in phenomenological psychiatry are represented. From the perspectives of research on consciousness, cognition and neurobiology of the temporal lobes with special emphasis on memory processes, the impact of time in depressive illness is investigated. Based on Freud's concept of "Todestrieb" (death-instinct) and "Nirvana-Prinzip" (nirvana-principle) with regard to the possible impact on a theory of forgetting--based on Michael Theunissens time-philosophical concept, which demonstrates coping of "dominance of time" i.e. intrusion of the past into the presence and the failure of these coping-processes in depressive patients--it is hypothesized, that "nirvana-energy" is a major constituent of processes for forgetting.

Humans↗

[Diagnostic steps in Alzheimer dementia before treatment with new antidimentives].

The dementia of the Alzheimer type (DAT) is a chronic neurodegenerative illness. It will continue to increase because of rising life expectancy in the industrialized countries. Apart from the physicians interest to treat, there is also an economically justified interest to reduce the disease progression in this group of patients. The main intention of the treating physicians is to keep their patients independent as long as possible. Up to now Alzheimer's disease can only be treated symptomatically. The verified diagnosis of DAT still depends on the neuropathological investigation of brain tissue. Therefore the clinical diagnosis of DAT during lifetime should be supported by chemical analysis of typical changes in the cerebrospinal fluid (CSF) at an early stage. Meanwhile, several therapeutics with proven effectiveness in clinical studies are certified for the symptomatic treatment of DAT. However, these therapeutics are still relatively expansive. Due to this fact the clinical diagnosis of DAT should be supported by clinical-chemical markers before the beginning of such a treatment. In this paper we present the diagnostic steps in dementia patients, who are examined in our departments. Patients suspicious of DAT always are asked for a spinal tap in addition to other diagnostic tools. In case of a typical clinical constellation, the exclusion of a primarily vascular dementia as well as the proof of decreased A beta 1-42 peptides and an increased tau protein in CSF we recommend the new drugs for DAT as meaningful and justified therapeutics to yield optimal treatment.

Aged↗

[The importance of the endogenous cannabinoid system in various neuropsychiatric disorders].

The endogenous cannabinoid system was first described in 1988. There are two specific receptors, the CB2-receptor, located in the lymphatic system (spleen, lymphocytes), and the CB1-receptor occurring predominantly in the central nervous system. The CB1-receptor shows a distinct distribution in the CNS with a very high density in the cerebellum, the basal ganglia and in the hippocampus. In 1992 endogenous ligands of the cannabinoid system were discovered for the first time (e.g. anandamide and 2-arachidonylglycerol). The physiological role of these arachidonic acid derivates is still unclear. Implications of these recent discoveries for the Gilles de la Tourette syndrome, ischaemic brain lesions, schizophrenic psychoses and opiate drug dependence are described. A dysregulation in the endogenous cannabinoid/anandamide system could possibly play an import role in the etiology of Gilles de la Tourette syndrome and schizophrenic psychoses; administration of cannabinoids affects the symptoms of the Gilles de la Tourette syndrome positively, whereas cannabinoids probably have rather negative effects in schizophrenic psychoses. In ischaemic brain lesions cannabinoids seem to have a neuroprotective effect; they appear to minimize the extent of a lesion by reduction of glutamate release. Additionally the meaning of the endogenous cannabinoid system for the development of opioid drug dependency is discussed and interactions between the endogenous opioid system and the endogenous cannabainoid system are pointed out. This is of interest since it could be shown in animal experiments that the absence of CB1 receptors reduces the positive reinforcement of opiate administration.

Animals↗

Word recognition memory before and after successful treatment of depression.

One of the most frequent and neuropsychologically well investigated symptoms in depression is reduced memory capacity. In this study, we investigated the course of disease in 16 patients with moderate depression and Borna disease virus (BDV) infection. Recently, it could be shown that BDV infection might play an important role in the etiology of subtypes of depression. Amantadine treatment was used as an antidepressant and antiviral compound. In order to assess memory capacity, event-related potentials (ERPs) were evaluated in ten of sixteen patients in a continuous word recognition experiment using a series of emotionally neutral, positive or negative words. During the treatment period the patients' clinical condition improved significantly. ERPs showed a reduced old/new effect before and after treatment independent of the words' emotional content. These findings suggest a reduced memory capacity being relatively independent of clinical outcome and ability to use emotional connotations for memory mechanisms. However, a significant positive shift over frontal electrodes did occur, which was concomitant with the improvement of depression, suggesting evidence for changed frontal cortical activity.

Adult↗

Acamprosate reduces motor cortex excitability determined by transcranial magnetic stimulation.

Acamprosate is effective in reducing alcohol intake in weaned alcoholics. We were interested if acamprosate had an effect on the excitability of cortical motoneurons determined by transcranial magnetic stimulation (TMS). We studied 12 male healthy volunteers (mean age 29.5 years, SD = 4.8) who were either treated with 6 tablets of acamprosate (each containing 333 mg verum) per day or placebo (randomized cross-over design) for 1 week. TMS was performed after each treatment session including a paired stimulation paradigm. Motor evoked potentials (MEPs) of the placebo and verum group did not differ with respect to paired stimulation. However, motor threshold increased in the acamprosate group (verum: 61.5% (SD = 7.9) vs. placebo: 58.9% (SD = 8.8), p = 0.036). We conclude that acamprosate leads to a hypoexcitability of the motor cortex. This might be due to subcortical mechanisms, e.g. thalamocortical pathways since intracortical inhibition and facilitation was not affected.

Acamprosate↗

Elevated endogenous cannabinoids in schizophrenia.

Evidence suggests that cannabinoid receptors, the pharmacologcial target of cannabis-derived drugs, and their accompanying system of endogenous activators may be dysfunctional in schizophrenia. To test this hypothesis, we examined whether endogenous cannabinoid concentrations in cerebrospinal fluid of schizophrenic patients are altered compared to nonschizophrenic controls. Endogenous cannabinoids were purified from cerebrospinal fluid of 10 patients with schizophrenia and 11 non-schizophrenic controls by high-performance liquid chromatography, and quantified by isotope dilution gas-chromatography/mass-spectrometry. Cerebrospinal concentrations of two endogenous cannabinoids (anandamide and palmitylethanolamide) were significantly higher in schizophrenic patients than non-schizophrenic controls (p < 0.05). By contrast, levels of 2-arachidonylglycerol, another endogenous cannabinoid lipid, were below detection in both groups. The findings did not seem attributable to gender, age or medication. Elevated anandamide and palmitylethanolamide levels in cerebrospinal fluid of schizophrenic patients may reflect an imbalance in endogenous cannabinoid signaling, which may contribute to the pathogenesis of schizophrenia.

Adult↗

Effects of synthetic delta9-tetrahydrocannabinol on binocular depth inversion of natural and artificial objects in man.

Binocular depth inversion represents an illusion of visual perception that is sensitive to various behavioural and psychiatric conditions. It is affected by cannabinoids, reflecting associated changes in perception. The present study investigated the differences in binocular depth inversion of different classes of natural and artificial objects and the effect of synthetic delta9-tetrahydrocannabinol (Dronabinol) on these illusionary perceptions. Using this model, the effects of orally administered Dronabinol on binocular depth inversion were investigated in 17 healthy male volunteers. Pictures from natural and artificial objects were presented stereoscopically and the depth perception of the volunteers was scored in an operationalized way. The timecourse of the effects of Dronabinol on binocular depth inversion was analyzed with regard to the stimulus classes (natural and synthetic objects). Significant differences in binocular depth inversion of the different groups of stimuli were revealed. Objects with a higher degree of everyday familiarity were generally seen as more illusionary than those with a lower degree of everyday familiarity. A strong impairment of binocular depth inversion due to Dronabinol was found in most classes of objects. Analysis of different stimulus classes provides further information on the underlying perceptual processing of binocular depth inversion. An impairment of top-down processing of visual sensory data by Dronabinol is suggested. The anandamidergic system seems to be involved in areas of visual information processing.

Adult↗

Possible use of amantadine in depression.

Amantadine, originally used in the treatment and prophylaxis of influenza infection, has also proved beneficial in drug-induced Parkinsonism, Parkinson's disease, traumatic head injury, dementia, multiple sclerosis and cocaine withdrawal. Amantadine appears to act through several pharmacological mechanisms, none of which has been identified as the one chief mode of action. It is a dopaminergic, noradrenergic and serotonergic substance, blocks monoaminoxidase A and NMDA receptors, and seems to raise beta-endorphin/beta-lipotropin levels. However, it is still uncertain which of these actions are relevant in therapeutic doses. One new aspect is the antiviral effect of amantadine on Borna disease virus, which it is suspected may possibly play a role in affective disorders. All of these actions could constitute an antidepressant property, and it is suggested that amantadine might work as an antidepressant not through one, but through several mechanisms thought to be related to antidepressant activity. Effects of amantadine on symptoms of affective disorders have been demonstrated in several trials administering it for varying purposes. Additionally, animal studies as well as clinical trials in humans have hinted at an antidepressant activity of amantadine. We present here an overview of the current data. However, only a limited body of evidence is available, and further studies are needed to investigate the efficacy of amantadine as well as its modes of action in depression.

Amantadine↗

Carbamazepine as an adjunct in the treatment of schizophrenia-like psychosis related to cannabis abuse.

The efficacy of an adjuvant application of carbamazepine in cannabis-related schizophrenia-like psychosis not responsive to neuroleptic treatment is reported for the first time. In two patients, psychotic states occurred after continuous cannabis consumption over a period of 8 and 18 months, respectively, which were mainly characterized by severe thought disorders, disturbances of perception, delusions and weak affect. Both patients were admitted to hospital with no previous clinical history of psychotic episodes. After nonresponsive treatment with neuroleptics over several weeks, they both rapidly responded to additional medication with carbamazepine within a week after onset with a marked reduction in clinical signs and symptoms.

Adult↗

Effects of fentanyl and low doses of alcohol on neuropsychological performance in healthy subjects.

The effects of the opioid fentanyl and low doses of alcohol on neuropsychological functions in healthy volunteers were measured. Twenty-four healthy male volunteers participated in this study. Two randomised placebo-controlled cross-over trials were conducted. In group 1, 6 subjects received fentanyl (0.2 microgram/kg body weight) in the order of fentanyl/placebo and 6 subjects in the order of placebo/fentanyl. Group 2 received alcohol in a similar procedure by continuous intravenous infusion, leading to a blood alcohol concentration (BAC) of 0.03%. Impairment was measured via different neuropsychological tests. The results indicate that fentanyl in concentrations commonly used in out-patient surgical procedures produces pronounced cognitive impairment (auditory reaction time, signal detection, sustained attention, recognition) in comparison to placebo. After application of low doses of alcohol (BAC 0.03%) only visual reaction time was impaired in comparison to placebo.

Adult↗

A syndrome of psychosis following discontinuation of an estrogen-progestogen contraceptive and improvement following replacement: A case report.

Mild forms of psychosis associated with low estrogen levels during the perimenopause are relatively frequent. There is scarce data on severe forms of psychosis in these conditions. We report the case of a 51-year-old woman with no previous psychiatric history who amputated her hand in a 'psychotiform' state after discontinuation of her contraceptive medication. Having subsequently jumped out of a window, she suffered a fracture of the dens with central spinal cord injury and symptoms of cruciate paralysis. The patient stabilized under a combined therapy with estrogen-progestogen substitution, antipsychotic medication and add-on oxcarbazepine.

Adult↗

Cannabis in movement disorders.

Central cannabinoid receptors are densely located in the output nuclei of the basal ganglia (globus pallidus, substantia nigra pars reticulata), suggesting their involvement in the regulation of motor activity. Furthermore, there is evidence that endogenous cannabinoid transmission plays a role in the manipulation of other transmitter systems within the basal ganglia by increasing GABAergic transmission, inhibiting glutamate release and affecting dopaminergic uptake. Most hyperkinetic and hypokinetic movement disorders are caused by a dysfunction of basal ganglia-thalamo-cortical loops. It has been suggested that an endogenous cannabinoid tone participates in the control of movements and, therefore, the central cannabinoid system might play a role in the pathophysiology of these diseases. During the last years in humans a limited number of clinical trials demonstrated that cannabinoids might be useful in the treatment of movement disorders. Despite the lack of controlled studies there is evidence that cannabinoids are of therapeutic value in the treatment of tics in Tourette syndrome, the reduction of levodopa-induced dyskinesia in Parkinson s disease and some forms of tremor and dystonia. It can be speculated that cannabinoid antagonists might be useful in the treatment of chorea in Huntington s disease and hypokinetic parkinsonian syndromes.

Basal Ganglia↗