Biomedical subjects

Peter Gass

Publications and source records attributed to Peter Gass.

At least 19 recordsLinked to original sources

PubMed2007

Differential regulation of neurotrophins and serotonergic function in mice with genetically reduced glucocorticoid receptor expression.

The neurotrophin and serotonin (5-HT) hypotheses of depression were studied in a mouse model of reduced glucocorticoid receptor (GR) function (GR(+/-) mice), which recently has been proven as a murine model of predisposition for depressive behaviour under stressful conditions. In this model we studied diurnal changes in neurotrophins and serotonergic function in candidate brain regions mediating depressive behaviour. Morning and evening levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were analyzed in representative brain regions of GR(+/-) and wildtype mice. The diurnal variation of hippocampal BDNF in wildtypes with higher levels in the morning was absent in GR(+/-) mice. Hypothalamus and parietal cortex displayed enhanced BDNF levels in GR(+/-) mice. In the frontal cortex, striatum and hypothalamus NGF increased from morning to evening in both genotypes, with an exaggeration in GR(+/-) mice. The diurnal variation of 5-HT levels and turnover did not differ significantly between genotypes. It was only in the hypothalamus that the evening level of 5-HIAA was lower in GR(+/-) mice than in wildtype mice. In conclusion, the present data indicate a contribution of altered BDNF and NGF protein levels to the predisposition for depressive behaviour in the GR(+/-) mouse model of depression, but argue against an eminent role of the serotonergic system.

Animals↗

PubMed2006

Increased risk of mental disorders among lifetime victims of stalking--findings from a community study.

PURPOSE: Population-based studies on the relationship between stalking and mental health outcomes in victims are scarce. The aim of the present study was to assess associations between stalking victimization and specific DSM-IV mental disorders in a community sample. METHOD: A postal survey was conducted in a middle-sized German city (sample size=675). Lifetime stalking victims and non-victims were compared regarding rates of any mental disorder, comorbid mental disorders, and specific disorders assessed by the Patient Health Questionnaire (PHQ). RESULTS: Victims had a higher incidence of mental disorders and comorbid mental disorders. Sex- and age-adjusted rates of specific disorders were increased, with the most robust associations identified for major depression (OR 4.8, 95% CI 1.8-12.8) and panic disorder (OR 4.1, 95% CI 1.1-14.9). Victims also reported higher current use of psychotropic medication (20.8% versus 5.6%). CONCLUSIONS: Our study indicates substantial associations between stalking victimization and impaired mental health that can be quantified at diagnostic levels in the general population. To confirm these findings, larger community studies are needed, which also include an assessment of lifetime psychopathology and of factors potentially mediating the associations between stalking victimization and mental health.

Adolescent↗

PubMed2006

What can we learn from the first community-based epidemiological study on stalking in Germany?

There is a lack of community-based studies on prevalence rates of stalking and the impact of stalking on victims in continental European countries. The authors published the first community-based epidemiological study on stalking in Germany. The purpose of this paper is to discuss possible implications of these epidemiological data for the mental health system, forensic psychiatry and legal regulations in Germany. For these reasons some data of our epidemiological study are outlined and reanalyzed. To examine lifetime and point prevalence rates of stalking, behavioural and psychological consequences for victims and the impact of stalking on current psychological well-being in a German community sample, a postal survey was conducted with 2000 inhabitants randomly selected from Mannheim (response rate 34.2%, n=679). The survey included a stalking questionnaire and the WHO-5 well-being scale. Almost 12% of the respondents reported having been stalked. This study identified a high lifetime prevalence of stalking in the community. Effects on victims' psychological health were significant and there was a high rate of physical (31%) and sexual (19%) violence in the context of stalking. Our data suggest that the phenomenon deserves more attention in future forensic psychiatric research and practice. Implications for forensic psychiatric assessment and treatment of stalkers as well as for management of stalking victims are discussed.

Adolescent↗

PubMed2006

Stress-resistant mice overexpressing glucocorticoid receptors display enhanced BDNF in the amygdala and hippocampus with unchanged NGF and serotonergic function.

Dysfunctional glucocorticoid receptor (GR) signaling has been shown to be involved in the pathogenesis of depressive behavior in mice and humans. In accordance with this hypothesis GR overexpressing mice are less susceptible to develop depressive-like behavior when subjected to stressful events. Here, we analyzed GR overexpressing mice for morning and evening content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and the tissue levels of serotonin and its metabolite 5-hydroxyindoleacetic acid) in brain areas suspected to be involved in stress adaptation. BDNF concentrations in the hippocampus and amygdala/piriform cortex were significantly enhanced in GR overexpressing mice (by maximally +103%) compared to wildtype animals. Diurnal variations, as detected for NGF in the hypothalamus, for BDNF in the frontal cortex and striatum and for serotonergic function in the frontal cortex and hypothalamus, were not affected by the genotype. In conclusion, GR overexpression-dependent increases of hippocampal and amygdala BDNF content presumably represent a dynamic correlate of enhanced stress resistance.

Amygdala↗

PubMed2006

Olfactory bulbectomy in mice leads to increased BDNF levels and decreased serotonin turnover in depression-related brain areas.

The olfactory bulbectomy in rodents has been proposed as an animal model for depression. According to the neurotrophin and monoamine hypotheses of depression, the present study examined neurotrophin and monoamine (serotonin, norepinephrine, dopamine) levels in several depression-related brain regions of mice subjected to olfactory bulbectomy. As expected, bulbectomized animals revealed behavioral alterations such as locomotor hyperactivity and reduced gain of bodyweight, regarded as correlates of a depressive-like state. Compared to sham-operated animals, bulbectomized mice demonstrated significantly increased brain-derived neurotrophic factor (BDNF), but regular nerve growth factor (NGF), protein levels in hippocampus (+108%) and frontal cortex (+48%) 16 days after olfactory bulbectomy. In these brain regions as well as in the hypothalamus, bulbectomy also caused a reduction of the molar ratio of 5-hydroxyindoleacetic acid to serotonin (5-HT) indicating a decrease in 5-HT turnover. Similarly, a hypofunction of the dopamine (DA) turnover was evident only in the hypothalamus in response to olfactory bulbectomy, presenting a decrease in the ratio 3,4 dihydroxyphenylacetic acid/DA with increased levels of DA. In all other brain areas investigated the levels of DA, its metabolite DOPAC and norepinephrine remained unaltered. Thus, olfactory bulbectomy seems to be a valid animal model also in mice related to serotonergic dysfunctions resembling bulbectomized rats that are a well-known model of hyposerotoninergic agitated depression. With respect to the common BDNF hypothesis of depression--predicting decreased BDNF expression in depression-related brain areas--the novel and challenging conclusions concern the increased BDNF protein levels in target regions of the cholinergic basal forebrain system in bulbectomized mice.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2006

IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors.

Cytokine-dependent mechanisms in the CNS have been implicated in the pathogenesis of depression. Interleukin-6 is upregulated in depressed patients and dowregulated by antidepressants. It is, however, unknown whether IL-6 is involved in the pathogenesis of depression. We subjected IL-6-deficient mice (IL-6(-/-)) to depression-related tests (learned helplessness, forced swimming, tail suspension, sucrose preference). We also investigated IL-6 in the hippocampus of stressed wild-type mice. IL-6(-/-) mice showed reduced despair in the forced swim, and tail suspension test, and enhanced hedonic behavior. Moreover, IL-6(-/-) mice exhibited resistance to helplessness. This resistance may be caused by the lack of IL-6, because stress increased IL-6 expression in wild-type hippocampi. This suggests that IL-6 is a component in molecular mechanisms in the pathogenesis of depression. IL-6(-/-) mice represent tools to study IL-6-dependent signaling pathways in the pathophysiology of depression in vivo. Moreover, these mice may support the screening of compounds for depression by altering cytokine-mediated signaling.

Animals↗

PubMed2006

[Mental health impact of stalking in men and women].

Using data from the Mannheim stalking study, the present report analyses gender differences with regard to various mental health indicators and potential mediator effects of stalking victimization. Furthermore, we were interested in whether the impact of stalking on mental health was comparable for men and women. The study included a postal survey of 675 community residents on the experience of intruding harassment and on mental health indicators. In the Patient Health Questionnaire (PHQ-D, Lowe et al. 2001), women scored higher on most of the subscales (depression, anxiety, somatic complaints, stress, psychosocial impairment) than men. Furthermore, more women fulfilled criteria for at least one threshold or subthreshold mental disorder syndrome according to DSM-IV, and more women were under psychotropic medication. However, the identified associations were completely mediated by the higher prevalence of stalking victims in women. In contrast, the associations of stalking victimization with poor mental health, psychosocial functioning, and use of medication were largely comparable across gender.

Adult↗

PubMed2006

Involvement of the AMPA receptor GluR-C subunit in alcohol-seeking behavior and relapse.

Craving and relapse are core symptoms of drug addiction and alcoholism. It is suggested that, after chronic drug consumption, long-lasting neuroplastic changes within the glutamatergic system are important determinants of addictive behavior. Here, we show that the AMPA type glutamate receptor plays a crucial role in alcohol craving and relapse. We observed, in two animal models of alcohol craving and relapse, that the AMPA antagonist GYKI 52466 [1-(4-aminophenyl)-4-methyl-7, 8-methylenedioxy-5H-2, 3-benzodiazepine] dose-dependently reduced cue-induced reinstatement of alcohol-seeking behavior and the alcohol deprivation effect. The involvement of the AMPA receptor in these phenomena was further studied using mice deficient for the GluR-C AMPA subunit [GluR-C knock-out (KO)]. GluR-C KOs displayed a blunted, cue-induced reinstatement response and alcohol deprivation effect, when compared with wild-type controls; however, no differences between genotypes could be observed regarding ethanol self-administration under operant or home cage drinking conditions. These results imply a role for GluR-C in alcohol relapse, although this phenotype could also be attributable to a reduction in the total number of AMPA receptors in specific brain areas. In conclusion, AMPA receptors seem to be involved in the neuroplastic changes underlying alcohol seeking behavior and relapse. Thus, AMPA receptors represent a novel therapeutic target in preventing relapse.

Alcoholism↗

PubMed2006

The epidemiology and characteristics of stalking.

PURPOSE OF REVIEW: This article summarizes major results in the field of epidemiology and characteristics of stalking, as published in literature between 2003 and October 2005. RECENT FINDINGS: Although stalking had been only recently conceptualized, it soon became evident that it represents a significant social and medical problem. Community-based studies on the prevalence of stalking are scarce and predominantly from English-speaking countries. All epidemiological studies, however, revealed that stalking is a widespread phenomenon with lifetime prevalence rates of stalking victimization ranging 12-16% among women and 4-7% among men. With regard to the impact of stalking, studies suggest that stalking can cause serious economic, social, medical and psychiatric consequences. Growing evidence suggests that serious violence and even homicide may occur in the context of stalking, and research on risk assessment has yielded an improved understanding of risk factors. Research on therapy of stalkers and stalking victims is still at its beginning; however, there are some preliminary reports with encouraging results. SUMMARY: Although there are research activities in the main fields, many basic questions still remain to be adequately addressed. Increased social and political awareness and expanded research funding are obligatory prerequisites to realize sound and well designed studies.

Crime Victims↗

PubMed2005

Social and structural housing conditions influence the development of a depressive-like phenotype in the learned helplessness paradigm in male mice.

Structural and social factors are known to play a crucial role in the pathogenesis of depression. Since animal models of depression are a major tool to gain insights into the mechanisms involved in the pathophysiology of this disease it is important not only to exploit but also to be aware of factors that may affect these models. As housing represents a fundamental external factor, which is controversially debated to affect the animals' emotionality, this study aimed to investigate the impact of different social and structural housing conditions on the development of a depressive-like syndrome in the learned helplessness paradigm. Group housing in an impoverished environment led to an increased vulnerability in the learned helplessness paradigm. Groups that were housed enriched, however, were less helpless. Furthermore impoverished conditions did not increase the vulnerability in single housed animals. Regarding emotionality in the animals, basal anxiety was reduced and the exploration was enhanced by group housing and enriched environment. These results suggest that housing conditions significantly influence the outcome of learned helplessness studies.

Animals↗

PubMed2005

Mice with genetically altered glucocorticoid receptor expression show altered sensitivity for stress-induced depressive reactions.

Altered glucocorticoid receptor (GR) signaling is a postulated mechanism for the pathogenesis of major depression. To mimic the human situation of altered GR function claimed for depression, we generated mouse strains that underexpress or overexpress GR, but maintain the regulatory genetic context controlling the GR gene. To achieve this goal, we used the following: (1) GR-heterozygous mutant mice (GR+/-) with a 50% GR gene dose reduction, and (2) mice overexpressing GR by a yeast artificial chromosome resulting in a twofold gene dose elevation. GR+/- mice exhibit normal baseline behaviors but demonstrate increased helplessness after stress exposure, a behavioral correlate of depression in mice. Similar to depressed patients, GR+/- mice have a disinhibited hypothalamic-pituitary-adrenal (HPA) system and a pathological dexamethasone/corticotropin-releasing hormone test. Thus, they represent a murine depression model with good face and construct validity. Overexpression of GR in mice evokes reduced helplessness after stress exposure, and an enhanced HPA system feedback regulation. Therefore, they may represent a model for a stress-resistant strain. These mouse models can now be used to study biological changes underlying the pathogenesis of depressive disorders. As a first potential molecular correlate for such changes, we identified a downregulation of BDNF protein content in the hippocampus of GR+/- mice, which is in agreement with the so-called neurotrophin hypothesis of depression.

Animals↗

PubMed2005

Mutant mouse models of depression: candidate genes and current mouse lines.

Depression is a multifactorial and multigenetic disease. At present, three main theories try to conceptualize its molecular and biochemical mechanisms, namely the monoamine-, the hypothalamus-pituitary-adrenal- (HPA-) system- and the neurotrophin-hypotheses. One way to explore, validate or falsify these hypotheses is to alter the expression of genes that are involved in these systems and study their respective role in animal behavior and neuroendocrinological parameters. Following an introduction in which we briefly describe each hypothesis, we review here the different mouse lines generated to study the respective molecular pathways. Among the many mutant lines generated, only a few can be regarded as genetic depression models or as models of predisposition for a depressive syndrome after stress exposure. However, this is likely to reflect the human situation where depressive syndromes are complex, can vary to a great extent with respect to their symptomatology, and may be influenced by a variety of environmental factors. Mice with mutations of candidate genes showing depression-like features on behavioral or neurochemical levels may help to define a complex molecular framework underlying depressive syndromes. Because it is conceivable that manipulation of one single genetic function may be necessary but not sufficient to cause complex behavioral alterations, strategies for improving genetic modeling of depression-like syndromes in animals possibly require a simultaneous targeted dysregulation of several genes involved in the pathogenesis of depression. This approach would correspond to the new concept of 'endophenotypes' in human depression research trying to identify behavioral traits which are thought to be encoded by a limited set of genes.

Animals↗

PubMed2005

[Prevalence of stalking in Germany].

AIMS: The present study aimed at gathering information on the lifetime prevalence and impact of stalking on victims in a German community. METHODS: A postal survey was sent to 1000 men and 1000 women who were sampled randomly from the inhabitant register. RESULTS: The lifetime prevalence of being a stalking victim was at 11.6 %. Compared to non-victims, stalking victims scored significantly poorer on the WHO-5 well-being index. CONCLUSIONS: Stalking seems to be a relevant problem in Germany. Physicians have to become experts in this issue since victims frequently ask them for help.

Adolescent↗

PubMed2005

Lifetime prevalence and impact of stalking in a European population: epidemiological data from a middle-sized German city.

BACKGROUND: There is a lack of community-based studies on prevalence rates of stalking and the impact of stalking on victims in European countries. AIMS: To examine lifetime and point prevalence rates of stalking, behavioural and psychological consequences for victims, and the impact of stalking on current psychological well-being in a German community sample. METHOD: A postal survey was conducted with a sample randomly selected from the population of a middle-sized German city; 679 people (400 women, 279 men) responded. The survey included a stalking questionnaire and the WHO-5 well-being scale. RESULTS: Almost 12% of the respondents (n=78, 68 women, 10 men) reported having been stalked. A multiple regression analysis revealed a significant effect of victimisation on psychological well-being. CONCLUSIONS: This study identified a high lifetime prevalence of stalking in the community. Effects on victims' psychological health are significant, suggesting that the phenomenon deserves more attention in future community mental health research.

Adaptation, Psychological↗

PubMed2004

Mice with a fra-1 knock-in into the c-fos locus show impaired spatial but regular contextual learning and normal LTP.

The immediate early gene c-fos is part of the AP-1 transcription factor complex, which is involved in molecular mechanisms underlying learning and memory. Mice that lack c-Fos in the brain show impairments in spatial reference and contextual learning, and also exhibit a reduced long-term potentiation of synaptic transmission (LTP) at CA3-to-CA1 synapses. In the present study, we investigated mice in which c-fos was deleted and replaced by fra-1 (c-fos(fra-1) mice) to determine whether other members of the c-fos gene family can substitute for the functions of the c-fos gene. In c-fos(fra-1) mice, both CA3-to-CA1 LTP and contextual learning in a Pavlovian fear conditioning task were similar to wild-type littermates, indicating that Fra-1 expression restored the impairments caused by brain-specific c-Fos depletion. However, c-Fos-mediated learning deficits in a reference memory task of the Morris watermaze were also present in c-fos(fra-1) mice. These findings suggest that different c-Fos target genes are involved in LTP, contextual learning, and spatial reference memory formation.

Animals↗

PubMed2004

Reduced expression of brain-derived neurotrophic factor in mice deficient for pituitary adenylate cyclase activating polypeptide type-I-receptor.

In vitro pituitary adenylate cyclase activating polypeptide (PACAP) induces the expression of brain-derived neurotrophic factor (BDNF) via its specific receptor PAC1. Since BDNF has been implicated in learning paradigms and mice lacking functional PAC1 have deficits in hippocampus-dependent associative learning, we investigated whether PAC1 mutants show alterations in hippocampal expression of BDNF and its receptor TrkB. Semi-quantitative in situ-hybridization using exon-specific BDNF-probes revealed significantly reduced expression of the exon-III and exon-V-specific transcripts within the hippocampal CA3 region in PAC1-deficient mice. A similar trend was observed for the exon-I-specific transcript. The expression of the exon-III-specific transcript was also reduced within the dentate gyrus, while Trk B-expression did not differ between genotypes. Our data demonstrate that even in vivo PAC1-mediated signaling seems to play a pivotal role for the transcriptional regulation of BDNF.

Animals↗

PubMed2004

Rats with congenital learned helplessness respond less to sucrose but show no deficits in activity or learning.

Inbred rat strains for congenital learned helplessness (cLH) and for congenital resistance to learned helplessness (cNLH) were investigated as a model to study genetic predisposition to major depression. Congenitally helpless rats respond less to sucrose under a progressive ratio schedule. This is not confounded by locomotor hypoactivity: in contrast, cLH rats show a slight hyperactivity during the first 5 min of an open field test. cLH rats acquire operant responding to sucrose as readily as cNLH rats and exhibit normal memory acquisition and retrieval in the Morris water maze, thus ruling out general learning deficits as the cause of the decreased response to sucrose. Reduced total responses and reduced breaking points for sucrose in the cLH strain argue for anhedonia, which is an analogue to loss of pleasure essential for the diagnosis of major depressive episodes, and thus confirm the validity of congenitally learned helpless rats as a model of major depression.

Animals↗

PubMed2004

Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior.

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.

Adrenocorticotropic Hormone↗