Biomedical subjects

F A Henn

Publications and source records attributed to F A Henn.

At least 37 records · Page 2Linked to original sources

PubMed2001

Stress differentially regulates synaptophysin and synaptotagmin expression in hippocampus.

BACKGROUND: In view of the effects of stress on synaptic plasticity, the regulation of synaptophysin and synaptotagmin expression by immobilization was analyzed by in situ hybridization. METHODS: Rats were exposed to immobilization stress, which induced typical behavioral alterations, such as reduced locomotor activity after stress exposure. Determination of mRNA levels of the integral synaptic vesicle proteins was performed immediately after acute or chronic immobilization. RESULTS: The results demonstrate that stress exposure leads to reduced expression of synaptophysin but increased expression of synaptotagmin in the hippocampus. CONCLUSIONS: This rapid and differential regulation of synaptic vesicle proteins could be responsible for some of the morphological, biochemical, and behavioral changes observed after stress exposure. These changes may be relevant to such clinical disorders as psychoses, depression, and posttraumatic stress disorder that are sensitive to stress and involve changes in neural and synaptic plasticity.

Animals↗

PubMed2001

Hippocampal 1H-MRSI in ecstasy users.

In recent years the illicit drug ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) has come into widespread use among young people. Despite clear evidence for the neurotoxic potential of MDMA in animals, corresponding evidence in humans is limited to indirect findings. In an exploratory study we compared the hippocampal 1H-MRSI (magnetic resonance spectroscopic imaging) spectra of five MDMA users with those of controls with no history of substance abuse. Although 1H

Adult↗

PubMed2001

Association analysis of HTR6 and HTR2A polymorphisms in sporadic Alzheimer's disease.

In order to identify gene variants related to the serotonergic neurotransmitter system that possibly represent a hereditary risk factor for sporadic Alzheimer's disease (AD), patients suffering from AD and non-demented psychiatric inpatients without symptoms of dementia were genotyped for polymorphisms of HTR6 (267C/T) and HTR2A (-1438G/A). Although there was a tendency toward an increased number of the genotype TT of the 5-HT6 receptor polymorphism in AD patients when compared to controls (2.8% vs. 1.3%), neither this nor the 5-HT2A promoter polymorphism showed significant differences in their genotypic or allelic distribution among patients and controls. These polymorphisms probably do not represent major genetic risk factors of AD. However, further studies including other genetic variants of the serotonergic neurotransmitter system are needed in order to elucidate their role in AD.

Alleles↗

PubMed2001

Learned helplessness in the rat: improvements in validity and reliability.

Major depression has a high prevalence and a high mortality. Despite many years of research little is known about the pathophysiologic events leading to depression nor about the causative molecular mechanisms of antidepressant treatment leading to remission and prevention of relapse. Animal models of depression are urgently needed to investigate new hypotheses. The learned helplessness paradigm initially described by Overmier and Seligman [J. Comp. Physiol. Psychol. 63 (1967) 28] is the most widely studied animal model of depression. Animals are exposed to inescapable shock and subsequently tested for a deficit in acquiring an avoidance task. Despite its excellent validity concerning the construct of etiology, symptomatology and prediction of treatment response [Clin. Neurosci. 1 (1993) 152; Trends Pharmacol. Sci. 12 (1991) 131] there has been little use of the model for the investigation of recent theories on the pathogenesis of depression. This may be due to reported difficulties in reliability of the paradigm [Animal Learn. Behav. 4 (1976) 401; Pharmacol. Biochem. Behav. 36 (1990) 739]. The aim of the current study was therefore to improve parameters for inescapable shock and learned helplessness testing to minimize artifacts and random error and yield a reliable fraction of helpless animals after shock exposure. The protocol uses mild current which induces helplessness only in some of the animals thereby modeling the hypothesis of variable predisposition for depression in different subjects [Psychopharmacol. Bull. 21 (1985) 443; Neurosci. Res. 38 (200) 193]. This allows us to use animals which are not helpless after inescapable shock as a stressed control, but sensitivity, specificity and variability of test results have to be reassessed.

Animals↗

PubMed2001

Thyroid function test abnormalities in newly admitted psychiatric patients residing in an iodine-deficient area: patterns and clinical significance.

OBJECTIVE: The prevalence of abnormal in-vitro thyroid function tests in psychiatric in-patients may be as high as 24%. Thus far, however, there is only limited data addressing the underlying causes of these abnormal test results, i.e. how often they can be attributed to genuine thyroid disease. METHOD: We conducted an observational study of all in-patients admitted to our institution during 1 calendar year running analyses of total thyroxin (T4), free thyroxin index (FTI) and thyroid-stimulating hormone (TSH). Patients with abnormal test results were classified according to an algorithm which had been established previously. RESULTS: In 243 of 880 patients with in-vitro thyroid function analysis, at least one concentration of either T4, FTI or TSH was found to be outside the reference range. Work-up according to the algorithm was completed in 848 patients; alterations were classified as representing thyroid dysfunction in 100 (41% of patients with abnormal test results), non-specific findings in 92 (38%), influence of ingested drugs in 18 (7%) and of severe physical disease in 1 (0.4%). As measures of T4 and/or FTI provided no essential information in 854 patients (97% of tested), we found that in most cases the determination of TSH alone was sufficient for demonstrating normal thyroid function. CONCLUSION: In 27.6% of newly admitted patients living in an iodine-deficient area, at least one abnormal result in either T4, FTI or TSH values was found. Genuine thyroid disease was found in slightly less than half the patients with an abnormal value.

Adolescent↗

PubMed2001

Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned helplessness.

Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.

Animals↗

PubMed2001

[Current overview of structural magnetic resonance imaging in schizophrenia].

Non-invasive morphologic imaging (computer tomography, magnetic resonance imaging, MRT) has contributed significantly to our understanding of schizophrenic disorders as diseases of the brain. Improved MRT techniques enable us to analyse anatomical substructures. The present overview evaluates peer-reviewed MRT studies published between 1994 and July 2000 and provides a comparison with our own results. Chronic schizophrenic patients most frequently show an enlargement in the ventricular system along with a reduction in grey matter. A more detailed subdivision into cortical and subcortical regions additionally shows the noted volume reduction to be limited to specific areas within the brain rather than being distributed equally throughout the brain. Within the area of the temporal lobes the two most frequently affected areas are the hippocampus and the gyrus temporalis superior. Alterations within these areas correlate with clinical symptoms such as hallucinations or thought disorders. Within the frontal cortex nearly 70% of all studies show a decrease in overall volume, while 63% note a reduction in size within the thalamus and 60% in the cerebellum. Morphologically speaking these structures therefore play the greatest role in the pathophysiology of schizophrenia and the onset of clinical symptoms. More recent studies also showed a specific progression in subgroups of patients pointing toward a neurodegenerative process. Additionally there are a number of differential antipsychotic effects following longterm treatment with typical neuroleptics as compared to atypical antipsychotics. Based on these findings future longitudinal studies should examine to what extent such a progressive decrease in volume might be influenced by treatment with modern antipsychotics.

Humans↗

PubMed2001

Favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics: an MRSI study.

In the present study, we evaluated 23 chronic schizophrenic patients under stable clinical conditions to determine the association between neuronal viability, as measured by in vivo(1)H magnetic resonance spectroscopic imaging (MRSI), and antipsychotic drug effects in the anterior cingulate cortex. Careful screening of the medication history showed that 11 of these patients had been treated with traditional neuroleptics only, while the others had switched to atypical antipsychotics due to non-response to traditional drugs. The group of patients receiving typical neuroleptic medication showed a mean NAA that was lower than in the group of patients receiving atypical antipsychotic drugs. Removing the duration of illness effect indicated a significant correlation between the NAA signal in the anterior cingulate gyrus and time on atypical drugs in patients under long-term atypical antipsychotic treatment. In contrast, patients with traditional medication revealed progressive decrease in the NAA level. These results suggest a favorable effect on neuronal viability in the anterior cingulate gyrus due to long-term treatment with atypical antipsychotics.

Adult↗

PubMed2001

Lower concentration of thalamic n-acetylaspartate in patients with schizophrenia: a replication study.

OBJECTIVE: Using proton magnetic resonance spectroscopic imaging, the authors measured thalamic N-acetylaspartate (NAA) concentrations in patients with schizophrenia. METHOD: The study included 15 schizophrenic patients on a stable medication regimen and 15 age-matched healthy comparison subjects. Concentrations of NAA, creatine plus phosphocreatine, and choline-containing compounds in bilateral thalamic regions were determined. RESULTS: Previous findings of lower NAA concentration in the left and right mediodorsal region of the thalamus and significant correlations between left and right thalamic NAA measures in patients with schizophrenia were corroborated. Furthermore, the concentrations of choline-containing compounds were significantly lower in the schizophrenic patients. No group differences in creatine plus phosphocreatine were found. CONCLUSIONS: There is strong evidence for neuronal dysfunction or loss in the mediodorsal region of the thalamus in patients with schizophrenia.

Adult↗

PubMed2000

Promoter polymorphism of the 5-HT transporter and Alzheimer's disease.

The role of the deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTT) is under discussion as a potential genetic risk factor for Alzheimers's disease (AD). Here we report significant differences in the allelic distribution of this polymorphism with a higher frequency of the short variant allele in AD patients when compared to controls. This difference was independent of the apolipoproteinE genotype. Thus, our study supports the notion that genetic alterations in the serontonergic neurotransmitter system may be involved in the etiopathogenesis of AD. However, given the reported negative findings, we are presently trying to identify diagnostic subgroups for which the 5-HTT promoter polymorphism represents a susceptibility locus.

Alleles↗

PubMed2000

Acute stress decreases serotonin transporter mRNA in the raphe pontis but not in other raphe nuclei of the rat.

In addition to elevated corticosterone levels, stress produces structural changes and neuronal damage especially in the hippocampus. In this line it has been shown, that in rats single or repeated immobilisation markedly reduces brain-derived neurotrophic factor (BDNF) mRNA levels in the hippocampal formation. Since this neurotrophin also controls the efficacy of serotonergic neurotransmission, the aim of the current study was to investigate the effect of acute immobilization stress on the expression of serotonin transporter (SERT) mRNA in the raphe nuclei as a parameter of serotonergic innervation. We have examined the expression of SERT mRNA and of BDNF mRNA in rats upon acute immobilisation by quantitative in situ hybridisation with a (35)S-labelled oligonucleotide probe. Elevated corticosterone levels in stressed animals confirmed as internal controls the effect of stress under our conditions. Acute stress led to a significant decrease of BDNF mRNA in the hippocampus and of SERT mRNA in the raphe pontis, but not in other raphe nuclei investigated. These data provide evidence for fast interactions between neurotrophins, corticosterone and serotonergic neurotransmission under stress conditions.

Animals↗

PubMed2000

Cortical response to motor stimulation in neuroleptic-naive first episode schizophrenics.

The purpose of the present study was to evaluate the cortical response to motor stimulation in neuroleptic-naive first episode schizophrenics in comparison to matched controls using a high speed functional magnetic resonance imaging technique (fMRI). Twelve patients satisfying ICD 10 criteria (F20.0) for schizophrenia (paranoid subtype) as well as sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examination on a conventional 1.5 T MR unit equipped with an echo-planar imaging booster. The blood oxygen level dependent (BOLD) response of the sensorimotor cortex and the higher order SMA region was evaluated during performance of a left hand sequential finger opposition task. Special care was taken to minimize performance and motion artifacts. Patients and controls showed no notable difference with respect to laterality, changes of signal intensity or spatial extent of activation within the primary and higher order motor regions. Using high speed fMRI no fundamental motor cortical dysfunction was evident in a group of paranoid neuroleptic-naive first episode schizophrenic patients. In contrast to data previously reported for chronic disorganized medicated patients, these results suggest that motor dysfunction is not part of the phenomenology of acute paranoid first episode patients.

Acute Disease↗

PubMed2000

Effects of age, medication, and illness duration on the N-acetyl aspartate signal of the anterior cingulate region in schizophrenia.

The authors performed a MRSI study of the anterior cingulate gyrus in 19 schizophrenic patients under stable medication and 16 controls in order to corroborate previous findings of reduced NAA in the anterior cingulate region in schizophrenia. Furthermore, correlations between NAA in the anterior cingulate gyrus and age or illness duration have been determined. A decreased NAA signal was found in the anterior cingulate gyrus of patients compared to controls. Subdividing the patient group into two groups depending on medication revealed that the group of patients receiving a typical neuroleptic medication showed a lower mean NAA in comparison to the group of patients receiving atypical antipsychotic drugs. No significant group differences in the creatine and phosphocreatine signal or the signal from choline-containing compounds were found. The NAA signal significantly correlated with age, and therefore, individual NAA values were corrected for the age effect found in the control group. The age-corrected NAA signal in schizophrenia correlated significantly with the duration of illness. The detected correlations of NAA decrease with age and illness duration are consistent with recent imaging studies where progressing cortical atrophy in schizophrenia was found. Further studies will be needed to corroborate a possible favorable effect of atypical antipsychotics on the NAA signal.

Adult↗

PubMed2000

The hippocampus in patients treated with electroconvulsive therapy: a proton magnetic resonance spectroscopic imaging study.

BACKGROUND: We monitored the effect of electroconvulsive therapy (ECT) on the nuclear magnetic resonance-detectable metabolites N-acetylaspartate, creatine and phosphocreatine, and choline-containing compounds in the hippocampus by means of hydrogen 1 magnetic resonance spectroscopic imaging. We hypothesized that if ECT-induced memory deterioration was associated with neuronal loss in the hippocampus, the N-acetylaspartate signal would decrease after ECT and any increased membrane turnover would result in an increase in the signal from choline-containing compounds. METHODS: Seventeen patients received complete courses of ECT, during which repeated proton magnetic resonance spectroscopic imaging studies of the hippocampal region were performed. Individual changes during the course of ECT were compared with values obtained in 24 healthy control subjects and 6 patients remitted from major depression without ECT. RESULTS: No changes in the hippocampal N-acetylaspartate signals were detected after ECT. A significant mean increase of 16% of the signal from choline-containing compounds after 5 or more ECT treatments was observed. Despite the mostly unilateral ECT application (14 of 17 patients), the increase in the choline-containing compound signal was observed bilaterally. Lactate or elevated lipid signals were not detected. All patients showed clinical amelioration of depression after ECT. CONCLUSIONS: Electroconvulsive therapy is not likely to induce hippocampal atrophy or cell death, which would be reflected by a decrease in the N-acetylaspartate signal. Compared with an age-matched control group, the choline-containing compounds signal in patients with a major depressive episode was significantly lower than normal, before ECT and normalized during ECT.

Adult↗

PubMed2000

Valproate as an adjunct to neuroleptic medication for the treatment of acute episodes of mania: a prospective, randomized, double-blind, placebo-controlled, multicenter study. European Valproate Mania Study Group.

To compare the efficacy of sodium valproate administered as adjunct to neuroleptic medication for patients with acute mania with the efficacy of neuroleptics alone, the authors conducted a 21-day, randomized, double-blind, parallel-group, placebo-controlled trial. The study design closely reflected a clinical psychiatric setting in Europe where patients with acute mania commonly receive neuroleptic medication. In this trial, 136 hospitalized patients met the ICD-10 criteria for acute manic episodes; these patients received a fixed dose of 20 mg/kg of body weight of sodium valproate (Orfiril, Desitin Arzneimittel GmbH, Hamburg, Germany) orally, in addition to basic neuroleptic medication, preferably haloperidol and/or perazine. The primary outcome measure was the mean dose of neuroleptic medication (after conversion into haloperidol-equivalents) for the 21-day study period. Severity of symptoms was measured using the Young Mania Rating Scale (YMRS), the Global Assessment Scale, and the Clinical Global Impression Scale. Intent-to-treat analysis was based on 69 patients treated with valproate and 67 patients who received placebo. Groups were comparable with regard to demographic and clinical baseline data. Premature discontinuations occurred in only 13% of the patients. The mean neuroleptic dose declined continuously in the valproate group, whereas only slight variations were observed in the placebo group; the difference was statistically significant (p = 0.0007) for study weeks 2 and 3. The combination of neuroleptic and valproate proved superior to neuroleptics in attempts to alleviate manic symptoms. The proportion of responders (a 50% improvement rate shown on the YMRS) was higher for the combination with valproate than for the group receiving only neuroleptics (70% vs. 46%; p = 0.005). Adverse events consisted of those known for valproate or neuroleptics; the only adverse event was asthenia, which occurred more frequently with the combination therapy. Valproate represents a useful adjunct medication for the treatment of acute manic symptoms. Valproate is beneficial because it allows the administration of fewer neuroleptic medications and produces improved and quicker remission of manic symptoms.

Acute Disease↗

PubMed2000

Genome polymorphism and alcoholism.

Different gene variants have been identified as risk or protective factors in alcoholism. The genes coding for dopamine receptors, serotonin transporters, and dehydrogenases represent susceptibility loci for addictive behaviour. However, alcoholism represents a complex psychiatric symptomatology which is caused by multiple factors, both genetic and environmental. Furthermore, there are probably different subtypes of alcoholism each with a distinct pathophysiology, and thus a different genetic background. Genetic research can help to identify such subtypes, which may require different therapeutic approaches. However, gene polymorphisms are not only responsible for a predisposition to alcoholism, but also for personality traits which influence the likelihood of developing addictive behaviour. Moreover, genetic polymorphisms are probably involved in the way an individual responds to treatment. Also, the severity of secondary diseases resulting from chronic alcohol uptake may depend on the genetic makeup of an individual. New treatment strategies focusing on genes contributing towards drug and alcohol dependence (such as gene therapy) are already under examination in animal models. However, further research is required before these developments will considerably change today's clinical handling of alcoholism.

Alcoholism↗

PubMed1999

Antipsychotic drug effects on motor activation measured by functional magnetic resonance imaging in schizophrenic patients.

Brain function and laterality in schizophrenia were investigated by means of a simple motor task with a self-generated left-hand sequential finger opposition (SFO) using a whole-brain high-speed (100 ms per slice) functional imaging technique. Neuroleptic-naïve, acutely ill schizophrenic patients were compared to schizophrenic patients under stable neuroleptic medication and matched controls. The goal was to evaluate both the motor function in first-episode patients and possible effects of different neuroleptic treatments on functional MRI results. Forty patients satisfying ICD 10 criteria (F20.x) for schizophrenia and sex- and age-matched healthy volunteers participated in this study. All subjects underwent fMRI examinations on a conventional 1.5 T MR unit. The primary sensorimotor cortex and the high-order supplementary motor area (SMA) were evaluated. There was a close similarity in the activation of the primary and high-order (SMA) sensorimotor areas between first-episode schizophrenic patients and controls. In contrast, a significant reduction in the overall blood oxygen level dependent (BOLD) response was seen in sensorimotor cortices (contra- and ipsilateral) in schizophrenic patients under stable medication with typical neuroleptics. This effect was not present in patients treated with atypical antipsychotics. Both antipsychotic treatments, however, led to a significant reduction in activation of the SMA region compared to controls and neuroleptic-naïve subjects. Thus, the present study provides no evidence for the localized involvement of the primary motor cortex or the SMA as a relatively stable vulnerability marker in schizophrenia. There is, however, strong evidence that neuroleptics themselves influence fMRI activation patterns and that there are major differences between typical neuroleptics and atypical antipsychotics.

Adult↗

PubMed1999

The calcium response of human T lymphocytes is decreased in aging but increased in Alzheimer's dementia.

BACKGROUND: A significant increase in the [Ca2+]i response of single T lymphocytes to mitogenic stimulation with phytohemagglutinin is reported for 27 Alzheimer patients compared with 27 healthy gender- and age-matched control subjects, regardless of gender. METHODS: The [Ca2+]i signals of T lymphocytes were assessed using the Fura-2-AM method. RESULTS: In Alzheimer's disease (AD) the reaction pattern is similar to that seen in a group of 27 young healthy control subjects who exhibited a marked [Ca2+]i rise after stimulation. During normal aging the reaction pattern of T cells is significantly attenuated in comparison to that found in young subjects. In healthy control subjects differences in age-related changes in calcium homeostasis are highly significant among women, young women showing the most intense cell response. CONCLUSIONS: The elevation of [Ca2+]i appears to be a prerequisite for apoptosis, which is suggested to be involved in the neuronal death occurring in AD. An increased [Ca2+]i in AD is consistent with processes leading to neurodegeneration in AD.

Adult↗