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2.
Sex Abuse ; 33(3): 274-294, 2021 Apr.
Article in English | MEDLINE | ID: mdl-31822196

ABSTRACT

This study explores the extent of sexual abuse of minors by members of the Catholic Church in Germany. It is the first comprehensive study to examine this extent in a European country. The goals of this study are as follows: (a) to analyze whether the extent and characteristics of sexual abuse in a European country are comparable to those in the United States and Australia and (b) how discrepancies can be explained. The personnel files of 38,156 Catholic Priests, deacons, and male members of religious orders in the authority of the German Bishops' Conference were analyzed. The study period lasted from 1946 to 2014. All 27 German dioceses took part in this study. A total of 4.4% of all clerics (N = 1,670) from 1946 to 2014 were alleged to have committed sexual abuse, and 3,677 children or adolescents were identified as victims. These results are similar to those from comparable studies in the United States. Sexual abuse of minors within the authority of the Catholic Church seems to be a worldwide phenomenon.


Subject(s)
Catholicism , Child Abuse, Sexual/statistics & numerical data , Clergy/statistics & numerical data , Records , Adolescent , Adult , Aged , Child , Crime Victims/statistics & numerical data , Female , Germany/epidemiology , Humans , Male , Middle Aged , Surveys and Questionnaires
3.
Eur Child Adolesc Psychiatry ; 29(9): 1277-1287, 2020 Sep.
Article in English | MEDLINE | ID: mdl-31811575

ABSTRACT

Stress is a mind-body phenomenon, which affects both mental and physical health and is highly relevant to the health care system. Yet, knowledge on the costs of stress and related health problems in adolescence is missing. The present study addresses this gap by investigating direct health care costs in relation to stress, mental health problems and physical health in high school students. The sample comprised 284 pupils from four schools in Heidelberg (mean age 16.75 ± 0.64 years, 59.64% female). Self-reported health care utilization and medication intake within 1 month were translated into costs. We established correlative associations of the dichotomized overall costs (no vs. any) with stress, mental health problems and physical health within generalized structural equation models. In particular, mental health problems and physical health were examined as mediators of the association between stress and costs. An increase of stress by 1 SD corresponded increased chances for costs by OR 1.39 (Odds Ratio; 95% CI 0.13-0.53, p = 0.001). When mediators were analysed separately, both mental and physical health (problems) fully mediated the association. Yet, when examined together, only mental health problems acted as a mediator. Our results indicate the health economic relevance of stress-related mental health problems in high school students. The finding is meant to set the stage for further cost-of-illness studies of stress and related health problems, as well as economic evaluations. Longitudinal research is needed to allow conclusions on directionality.


Subject(s)
Health Care Costs/statistics & numerical data , Mental Disorders/psychology , Mental Health/economics , Stress, Psychological/psychology , Students/psychology , Adolescent , Child , Female , Germany , Humans , Male , Schools
4.
Ther Adv Neurol Disord ; 12: 1756286419887596, 2019.
Article in English | MEDLINE | ID: mdl-31832100

ABSTRACT

BACKGROUND: The humanized anti-α4 integrin monoclonal antibody natalizumab has proven to be very effective in patients with highly active relapsing-remitting multiple sclerosis (MS), but harbors the risk of progressive multifocal leukoencephalopathy (PML). Recently, new therapeutic options have become available for patients with high risk of developing PML while on natalizumab treatment. One of these new therapeutics is the oral synthetic purine analogue cladribine. In order to determine whether therapy with cladribine is effective and safe in patients with MS who previously had been treated with natalizumab, we analyzed clinical, radiological, and laboratory data of 17 patients whose disease modifying treatment (DMT) was switched from natalizumab to cladribine. METHODS: A total of 17 patients with prior natalizumab treatment were switched to a DMT with cladribine because of a John Cunningham virus (JCV) antibody index above 1.5 (N = 13), ongoing disease activity (N = 6), magnetic resonance imaging (MRI) disease activity (N = 4), or patients preference (N = 2). A chart review and follow up of those patients was performed. In addition to MRI and laboratory data, clinical data regarding MS relapses and disease progression or possible adverse events were analyzed. RESULTS: The median duration of cladribine treatment between February 2018 and April 2019 amounted to 9.7 months (range: 1.5-15 months). None of our 17 patients presented with a clinical relapse. Only two patients showed a new T2 lesion on brain MRI, but without any signs of PML. As expected, reduction of lymphocyte count was frequent in cladribine-treated patients, but only four patients exhibited lymphopenia grade 2 (500-800/µl). CONCLUSIONS: In our cohort the switch from natalizumab to cladribine treatment was effective and safe. So far, no serious adverse events other than lymphopenia have been observed, especially no cases of PML.

5.
Dtsch Arztebl Int ; 116(22): 389-396, 2019 May 31.
Article in English | MEDLINE | ID: mdl-31366429

ABSTRACT

BACKGROUND: When cases of sexual abuse within the Catholic Church became known, the German Bishops' Conference (Deutsche Bischofskonferenz, DBK) commissioned a study by an interdisciplinary consortium to determine the frequency of sexual abuse by Catholic clergy in Germany (the MHG study). METHODS: Qualitative and quantitative research methods were used and the subject matter of the study was analyzed in seven component projects. To determine the frequency of sexual abuse, 38 156 personnel files of Catholic clergy from the period 1946 to 2014 were studied, and the epidemiologic findings of these evaluations are presented. RESULTS: 1670 persons belonging to the Catholic clergy who were accused of sexual abuse of minors were identified from their personnel files, corresponding to 4.4% of the clergy overall. 3677 victims of sexual abuse could be linked to the accused persons; 62.8% of them were male, and 66.7% were under 14 years old when the abuse took place. The mean duration of the abuse in individual cases was 1.3 years. "Hands-on" abuses (i.e., abuses involving bodily contact) occurred in more than 80% of cases. Many of the affected persons suffered serious consequences for their health and social functioning. The ones most commonly reported were anxiety, depression, mistrust, sexual problems, and difficulties with interpersonal contact. CONCLUSION: The figures reported here should be considered a lower bound to the actual frequency of sexual abuse. Asymmetrical power relationships in a closed system such as the Catholic Church can facilitate sexual abuse. Physicians play an important role in the diagnosis and treatment of the victims of sexual abuse, in the diagnosis and treatment of persons inclined to commit abuses and actual abusers, and in the development and implementation of preventive strategies.


Subject(s)
Child Abuse, Sexual , Child Abuse , Clergy , Adolescent , Catholicism , Child , Female , Germany , Humans , Male
6.
Psychiatr Prax ; 46(5): 256-262, 2019 Jul.
Article in German | MEDLINE | ID: mdl-31269519

ABSTRACT

OBJECTIVE: This paper explores the frequency of sexual abuse allegations against Catholic priests and deacons in the years 2009 to 2015 in relation to the male general population in Germany. METHOD: An annual rate of sexual abuse accusations is calculated from the sexual abuse allegations against Catholic priests identified in the MHG-study for the years 2009 to 2015. This is compared to figures of the male general population from the police crime statistics. RESULTS: The number of suspected men in the general population ranged from 17.6 - 20.0/100.000 between 2009 and 2015. For Catholic priests the rate of accusations ranged from 8.4 to 31.7/100.000. A decrease of the quota was not detectable in either group during the study period. DISCUSSION: The findings suggest that there is a relatively constant rate of people being disposed to child sexual abuse in the group of Catholic priests. These results should be addressed specifically in the prevention work of the Catholic Church.


Subject(s)
Catholicism , Child Abuse, Sexual , Clergy , Child , Germany , Humans , Male
7.
Trials ; 20(1): 53, 2019 Jan 15.
Article in English | MEDLINE | ID: mdl-30646944

ABSTRACT

BACKGROUND: Depression is a serious mental health problem and is common in children and adolescents. Online interventions are promising in overcoming the widespread undertreatment of depression and in improving the help-seeking behavior in children and adolescents. METHODS: The multicentre, randomized controlled E.motion trial is part of the German ProHEAD consortium (Promoting Help-seeking using E-technology for ADolescents). The objective of the trial is to investigate the efficacy and cost-effectiveness of two online interventions to reduce depressive symptomatology in high-risk children and adolescents with subsyndromal symptoms of depression in comparison to an active control group. Participants will be randomized to one of three conditions: (1) Intervention 1, a clinician-guided self-management program (iFightDepression®); (2) Intervention 2, a clinician-guided group chat intervention; and (3) Control intervention, a psycho-educational website on depressive symptoms. Interventions last six weeks. In total, N = 363 children and adolescents aged ≥ 12 years with Patient Health Questionnaire-9 modified for Adolescents (PHQ-A) scores in the range of 5-9 will be recruited at five study sites across Germany. Online questionnaires will be administered before onset of the intervention, at the end of the intervention, and at the six-month follow-up. Further, children and adolescents will participate in the baseline screening and the one- and two-year school-based follow-up assessments integrated in the ProHEAD consortium. The primary endpoint is depression symptomatology at the end of intervention as measured by the PHQ-A score. Secondary outcomes include depression symptomatology at all follow-ups, help-seeking attitudes, and actual face-to-face help-seeking, adherence to and satisfaction with the interventions, depression stigma, and utilization and cost of interventions. DISCUSSION: This study represents the first randomized controlled trial (RCT) investigating efficacy and cost-effectiveness of two online interventions in children and adolescents aged ≥ 12 years at risk for depression. It aims to provide a better understanding of the help-seeking behavior of children and adolescents, potential benefits of E-mental health interventions for this age group, and new insights into so far understudied aspects of E-mental health programs, such as potential negative effects of online interventions. This knowledge will be used to tailor and improve future help offers and programs for children and adolescents and ways of treatment allocation. TRIAL REGISTRATION: German Register for Clinical Trials (DRKS), DRKS00014668 . Registered on 4 May 2018. International trial registration took place through the "international clinical trials registry platform" with the secondary ID S-086/2018.


Subject(s)
Adolescent Behavior , Affect , Child Behavior , Depression/therapy , Internet , Telemedicine/methods , Therapy, Computer-Assisted/methods , Adolescent , Age Factors , Child , Cost-Benefit Analysis , Depression/diagnosis , Depression/economics , Depression/psychology , Germany , Health Care Costs , Humans , Internet/economics , Multicenter Studies as Topic , Patient Health Questionnaire , Randomized Controlled Trials as Topic , Self Care , Telemedicine/economics , Therapy, Computer-Assisted/economics , Time Factors , Treatment Outcome
8.
J Appl Res Intellect Disabil ; 31(2): 285-295, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28834006

ABSTRACT

BACKGROUND: Adults with an intellectual disability should be supported according to their individual needs. The perception of need, however, is influenced by the values and expectations of the judging person. METHOD: Using the Camberwell Assessment of Need for Adults with Developmental and Intellectual Disabilities, self- and proxy-rated needs of n = 193 adults with mild to moderate intellectual disability were compared. RESULTS: Mean total needs and met needs, but not unmet needs, differed significantly between perspectives. As concerns the assessment of specific areas of need, indices revealed a complex and multifaceted pattern of agreement and disagreement. CONCLUSION: Different viewpoints should be considered when assessing needs among adults with intellectual disability. With respect to areas other than basic, everyday areas of need, involvement of the adult with intellectual disability is strongly recommended. The assessment of mental health problems requires the involvement of clinical professionals, assessing problem behavior broad diagnostic measures beyond a standardized instrument.


Subject(s)
Health Services Needs and Demand , Intellectual Disability/psychology , Needs Assessment , Adolescent , Adult , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Young Adult
9.
Psychiatr Prax ; 45(2): 103-105, 2018 03.
Article in German | MEDLINE | ID: mdl-28724163

ABSTRACT

OBJECTIVE: A subproject of the study "Sexual abuse of minors by Catholic priests and deacons in the authority of the German Bishops' conference" deals with aspects of prevention. METHOD: Structured questions were used to record objective data on preventive work. The questionnaire was completed in all 27 dioceses of Germany. RESULTS: The average hourly rate available for the work of the prevention officers is about 30 hours per week. At the end of 2014, 59 % of clerics were involved in preventive training. The temporal extent of prevention training differs greatly between individual dioceses. DISCUSSION: The Catholic Church of Germany has undertaken extensive efforts to implement a comprehensive prevention work to avoid sexual abuse of minors within catholic institutions. However, there are considerable differences between the individual dioceses.


Subject(s)
Catholicism , Child Abuse, Sexual , Clergy/psychology , Child , Child Abuse, Sexual/prevention & control , Germany , Group Processes , Humans
10.
J Neurol ; 263(12): 2499-2504, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27730374

ABSTRACT

The majority of patients presenting with a first clinical symptom suggestive of multiple sclerosis (MS) do not fulfill the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS and are thus classified as clinically isolated syndrome (CIS). To re-evaluate the utility of cerebrospinal fluid (CSF) analysis in the context of the revised McDonald criteria from 2010, we conducted a retrospective multicenter study aimed at determining the prevalence and predictive value of oligoclonal IgG bands (OCBs) in patients with CIS. Patients were recruited from ten specialized MS centers in Germany and Austria. We collected data from 406 patients; at disease onset, 44/406 (11 %) fulfilled the McDonald 2010 criteria for MS. Intrathecal IgG OCBs were detected in 310/362 (86 %) of CIS patients. Those patients were twice as likely to convert to MS according to McDonald 2010 criteria as OCB-negative individuals (hazard ratio = 2.1, p = 0.0014) and in a shorter time period of 25 months (95 % CI 21-34) compared to 47 months in OCB-negative individuals (95 % CI 36-85). In patients without brain lesions at first attack and presence of intrathecal OCBs (30/44), conversion rate to MS was 60 % (18/30), whereas it was only 21 % (3/14) in those without OCBs. Our data confirm that in patients with CIS the risk of conversion to MS substantially increases if OCBs are present at onset. CSF analysis definitely helps to evaluate the prognosis in patients who do not have MS according to the revised McDonald criteria.


Subject(s)
Multiple Sclerosis/cerebrospinal fluid , Multiple Sclerosis/diagnosis , Oligoclonal Bands/cerebrospinal fluid , Severity of Illness Index , Adult , Austria/epidemiology , Disease Progression , Female , Germany/epidemiology , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Multiple Sclerosis/mortality , Retrospective Studies
11.
Soc Psychiatry Psychiatr Epidemiol ; 51(5): 767-76, 2016 05.
Article in English | MEDLINE | ID: mdl-26952326

ABSTRACT

PURPOSE: Mental ill health in adults with intellectual disability (ID) is a neglected field in psychiatry and thus still widely understudied. This paper provides data on the prevalence of mental illness and problem behaviour and analyses support needs, mental health service use and psychotropic medication in a representative sample of adults with mild to moderate ID. METHODS: A set of well-established instruments was used to assess the main parameters in n = 371 participants recruited within a cross-sectional epidemiological multicentre study using a stratified randomised cluster sampling. RESULTS: Point prevalence of mental disorders was 10.8 %, that of problem behaviour 45.3 %. Most study participants needed help in specific lower order need areas (e.g., money budgeting, food, accommodation), and these need areas were mostly rated as met. The highest ratios of unmet to met need were found with respect to sexuality issues and with respect to mental health problems. The focus of psychiatric treatment was psychotropic medication. CONCLUSIONS: Referring to ICD-10 based diagnostic criteria and consequently avoiding confusing problem behaviour with mental disorders, point prevalence of mental disorders was lower than in the general population. A systematic deficit in meeting mental health problems in adults with ID indicates the need for implementing strategies to maximise the quality of identification and management of mental disorders.


Subject(s)
Intellectual Disability/epidemiology , Intellectual Disability/psychology , Mental Disorders/epidemiology , Mental Disorders/psychology , Mental Health Services/statistics & numerical data , Needs Assessment/statistics & numerical data , Problem Behavior/psychology , Adult , Aged , Cross-Sectional Studies , Female , Germany , Humans , Male , Middle Aged , Utilization Review/statistics & numerical data , Young Adult
12.
Psychiatr Prax ; 43(7): 380-386, 2016 Oct.
Article in German | MEDLINE | ID: mdl-26488265

ABSTRACT

Objective: Within the MEMENTA-study informal caregivers of grown-up persons with an intellectual disability (ID) with and without a comorbid mental disorder were interviewed. Main outcomes were family burden, quality of life, psychiatric symptomatology and problem behavior. Methods: The sample consisted of 123 informal caregivers. Results: Problem behavior was associated with a higher family burden than psychiatric symptomatology. Conclusion: Rather than mental disorders, problem behavior seemed to be more relevant for the experience of family burden.


Subject(s)
Caregivers/psychology , Intellectual Disability/psychology , Intellectual Disability/therapy , Mental Disorders/psychology , Mental Disorders/therapy , Adolescent , Adult , Aged , Comorbidity , Cross-Sectional Studies , Expressed Emotion , Family Conflict/psychology , Female , Germany , Humans , Intellectual Disability/diagnosis , Intellectual Disability/epidemiology , Interview, Psychological , Male , Mental Disorders/diagnosis , Mental Disorders/epidemiology , Middle Aged , Quality of Life/psychology , Social Behavior Disorders/diagnosis , Social Behavior Disorders/epidemiology , Social Behavior Disorders/psychology , Social Behavior Disorders/therapy , Surveys and Questionnaires , Young Adult
13.
Res Dev Disabil ; 45-46: 136-46, 2015.
Article in English | MEDLINE | ID: mdl-26233765

ABSTRACT

Proxies often underestimate the subjective Quality of Life (QoL) of adults with intellectual disability (ID). However, little is known about the reasons for these differences. Accordingly, the purpose of the present study is to, firstly, compare the self-reported QoL of adults with ID with proxy reports from staff of sheltered working and housing facilities, and, secondly, to identify possible differences of the impact of four potential predictor variables. Data of 102 adults with ID were collected as part of the MEMENTA study ('Mental health care provision for adults with ID and a mental disorder'). Results show that self-report QoL scores ranged from 72.6 to 86.8. Both proxies consistently reported lower QoL scores and agreement between self and proxy ratings was predominantly poor. Unmet needs and psychotropic medication were identified as the most important predictors of reduced self-rated QoL, whereas an increase of psychiatric symptoms, problem behaviours, and psychotropic medication best predicted the reduced QoL proxy ratings. To conclude, proxies still have to strive for a more holistic approach in surrogate QoL assessments and according to adults with ID, service providers should focus on a reduction of unmet needs and psychotropic medication to further improve QoL.


Subject(s)
Intellectual Disability/psychology , Mental Disorders/psychology , Problem Behavior/psychology , Proxy , Quality of Life/psychology , Self Report , Adolescent , Adult , Aged , Female , Humans , Linear Models , Male , Mental Disorders/drug therapy , Mental Health , Middle Aged , Needs Assessment , Psychotropic Drugs/therapeutic use , Residence Characteristics , Sheltered Workshops , Young Adult
14.
Brain ; 138(Pt 2): 398-413, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25524711

ABSTRACT

Neuroprotective approaches for central nervous system regeneration have not been successful in clinical practice so far and compounds that enhance remyelination are still not available for patients with multiple sclerosis. The objective of this study was to determine potential regenerative effects of the substance cytidine-5'-diphospho (CDP)-choline in two different murine animal models of multiple sclerosis. The effects of exogenously applied CDP-choline were tested in murine myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. In addition, the cuprizone-induced mouse model of de- and remyelination was used to specifically test the hypothesis that CDP-choline directly increases remyelination. We found that CDP-choline ameliorated the disease course of experimental autoimmune encephalomyelitis and exerted beneficial effects on myelin, oligodendrocytes and axons. After cuprizone-induced demyelination, CDP-choline effectively enhanced myelin regeneration and reversed motor coordination deficits. The increased remyelination arose from an increase in the numbers of proliferating oligodendrocyte precursor cells and oligodendrocytes. Further in vitro studies suggest that this process is regulated by protein kinase C. We thus identified a new mechanism to enhance central nervous system remyelination via the choline pathway. Due to its regenerative action combined with an excellent safety profile, CDP-choline could become a promising substance for patients with multiple sclerosis as an add-on therapy.


Subject(s)
Choline/metabolism , Demyelinating Diseases/chemically induced , Demyelinating Diseases/metabolism , Myelin Sheath/drug effects , Animals , Cell Proliferation/drug effects , Chelating Agents , Cuprizone , Cytidine Diphosphate Choline/pharmacology , Mice , Mice, Inbred C57BL , Neural Stem Cells/drug effects , Neuroglia/drug effects , Nootropic Agents/pharmacology , Oligodendroglia/drug effects , Rats , Rats, Sprague-Dawley , T-Lymphocytes/drug effects
15.
J Appl Gerontol ; 34(1): 3-25, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25548086

ABSTRACT

This study explores differences in the out-of-home behavior of community-dwelling older adults with different cognitive impairment. Three levels of complexity of out-of-home behavior were distinguished: (a) mostly automatized walking behavior (low complexity), (b) global out-of-home mobility (medium complexity), and (c) defined units of concrete out-of-home activities, particularly cognitively demanding activities (high complexity). A sample of 257 older adults aged 59 to 91 years (M = 72.9 years, SD = 6.4 years) included 35 persons with early-stage Alzheimer's disease (AD), 76 persons with mild cognitive impairment (MCI), and 146 cognitively healthy persons (CH). Mobility data were gathered by using a GPS tracking device as well as by questionnaire. Predicting cognitive impairment status by out-of-home behavior and a range of confounders by means of multinomial logistic regression revealed that only cognitively demanding activities showed at least a marginally significant difference between MCI and CH and were highly significant between AD and CH.


Subject(s)
Activities of Daily Living , Alzheimer Disease/psychology , Cognition , Cognitive Dysfunction/psychology , Geriatric Assessment/statistics & numerical data , Aged , Aged, 80 and over , Female , Geographic Information Systems , Geriatric Psychiatry , Humans , Logistic Models , Male , Middle Aged , Mobility Limitation , Quality of Life , Surveys and Questionnaires , Walking
16.
J Appl Gerontol ; 34(1): 26-47, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25548087

ABSTRACT

This study explores the relationship between out-of-home behavior and daily mood of community-dwelling older adults with different levels of cognitive impairment across four consecutive weeks. The sample included 16 persons with early stage Alzheimer's disease (AD), 30 persons with mild cognitive impairment (MCI), and 95 cognitively healthy persons (CH). Using a multi-method approach, GPS tracking and daily-diary data were combined on a day-to-day basis. AD and MCI adults showed lower mood than the CH group. Whereas stronger positive links between mood and out-of-home behavior were found for AD compared to the total sample on an aggregate level, predicting daily mood by person (i.e., cognition) and occasion-specific characteristics (i.e., mobility and weekday), using multilevel regression analysis revealed no corresponding effect. In conclusion, cognitive status in old age appears to impact on mobility and mood as such, rather than on the mood and out-of-home behavior connection.


Subject(s)
Activities of Daily Living , Affect , Alzheimer Disease/psychology , Cognition , Cognitive Dysfunction/psychology , Aged , Aged, 80 and over , Female , Geographic Information Systems , Geriatric Assessment , Geriatric Psychiatry , Humans , Male , Middle Aged , Mobility Limitation , Regression Analysis
17.
BMC Neurol ; 14: 136, 2014 Jun 20.
Article in English | MEDLINE | ID: mdl-24950993

ABSTRACT

BACKGROUND: Pathogenic autoantibodies targeting the recently identified leucine rich glioma inactivated 1 protein and the subunit 1 of the N-methyl-D-aspartate receptor induce autoimmune encephalitis. A comparison of brain metabolic patterns in 18F-fluoro-2-deoxy-d-glucose positron emission tomography of anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis patients has not been performed yet and shall be helpful in differentiating these two most common forms of autoimmune encephalitis. METHODS: The brain 18F-fluoro-2-deoxy-d-glucose uptake from whole-body positron emission tomography of six anti-N-methyl-D-aspartate receptor encephalitis patients and four patients with anti-leucine rich glioma inactivated 1 protein encephalitis admitted to Hannover Medical School between 2008 and 2012 was retrospectively analyzed and compared to matched controls. RESULTS: Group analysis of anti-N-methyl-D-aspartate encephalitis patients demonstrated regionally limited hypermetabolism in frontotemporal areas contrasting an extensive hypometabolism in parietal lobes, whereas the anti-leucine rich glioma inactivated 1 protein syndrome was characterized by hypermetabolism in cerebellar, basal ganglia, occipital and precentral areas and minor frontomesial hypometabolism. CONCLUSIONS: This retrospective 18F-fluoro-2-deoxy-d-glucose positron emission tomography study provides novel evidence for distinct brain metabolic patterns in patients with anti-leucine rich glioma inactivated 1 protein and anti-N-methyl-D-aspartate receptor encephalitis.


Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis/diagnostic imaging , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/metabolism , Brain Chemistry/physiology , Encephalitis/diagnostic imaging , Encephalitis/metabolism , Glucose/metabolism , Proteins/immunology , Adult , Aged , Anti-N-Methyl-D-Aspartate Receptor Encephalitis/psychology , Autoantibodies/immunology , Encephalitis/immunology , Female , Fluorodeoxyglucose F18 , Humans , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Positron-Emission Tomography , Radiopharmaceuticals , Reproducibility of Results , Retrospective Studies
18.
Brain ; 136(Pt 1): 147-67, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23266461

ABSTRACT

Recent evidence suggests that astrocytes play an important role in regulating de- and remyelination in multiple sclerosis. The role of astrocytes is controversial, and both beneficial as well as detrimental effects are being discussed. We performed loss-of-function studies based on astrocyte depletion in a cuprizone-induced rodent model of demyelination. This led to strong astrogliosis accompanied by microgliosis and demyelination in C57BL/6 wild-type mice. Ablation of astrocytes in glial fibrillary acidic protein-thymidine kinase transgenic mice was associated with a failure of damaged myelin removal and a consecutive delay in remyelination. Despite oligodendrocyte death, myelin was still present, but ultrastructual investigations showed that the myelin structure was loosened and this damaged myelin did not protect axons. These alterations were associated with a decrease in microglial activation. Thus, our results show that astrocyte loss does not prevent myelin damage, but clearance of damaged myelin through recruitment of microglia is impaired. Further studies suggest that this process is regulated by the chemokine CXCL10. As a consequence of the delayed removal of myelin debris, remyelination and oligodendrocyte precursor cell proliferation were impaired. Experiments omitting the influence of myelin debris demonstrated an additional beneficial effect of astrocytes on oligodendrocyte regeneration during remyelination. In conclusion, these data demonstrate for the first time in vivo that astrocytes provide the signal environment that forms the basis for the recruitment of microglia to clear myelin debris, a process required for subsequent repair mechanisms. This is of great importance to understanding regenerative processes in demyelinating diseases such as multiple sclerosis.


Subject(s)
Astrocytes/metabolism , Demyelinating Diseases/metabolism , Microglia/metabolism , Myelin Sheath/metabolism , Nerve Fibers, Myelinated/metabolism , Animals , Astrocytes/pathology , Axons/metabolism , Axons/pathology , Brain/metabolism , Brain/pathology , Corpus Callosum/metabolism , Corpus Callosum/pathology , Corpus Callosum/physiopathology , Cuprizone , Demyelinating Diseases/chemically induced , Demyelinating Diseases/pathology , Glial Fibrillary Acidic Protein , Gliosis/metabolism , Gliosis/pathology , Gliosis/physiopathology , Male , Mice , Mice, Transgenic , Microglia/pathology , Myelin Sheath/pathology , Nerve Fibers, Myelinated/pathology , Nerve Regeneration/physiology , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism
19.
J Gerontol B Psychol Sci Soc Sci ; 68(5): 691-702, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23197344

ABSTRACT

OBJECTIVES: We examined in this study the hypothesis that cognitive resources are more closely linked with out-of-home behavior than motivational resources. METHOD: A cognitively heterogeneous sample of 222 older adults aged 59-91 years (M = 72.7; SD = 6.2), including 146 cognitively healthy persons and 76 persons with mild cognitive impairment-recruited in the German and Israeli arm of the SenTra project-was used for the analysis. Out-of-home behavior was assessed by means of global positioning system technology (time out of home; number of nodes visited) as well as by questionnaire (out-of-home activities). Mini-Mental State Examination and trail-making tests A and B were used to assess cognitive resources. Well-being, depression, and environmental mastery were assessed as motivational resources. RESULTS: Findings at the zero-order and latent variable levels confirmed that cognitive resources were more closely linked with out-of-home behavior than motivational resources. DISCUSSION: Findings support the view that well-being-related motivations to exert out-of-home behavior may become less important in old age because of the increasing cognitive resources required by such behavior.


Subject(s)
Cognition , Motivation , Activities of Daily Living/psychology , Aged , Aged, 80 and over , Cognitive Dysfunction/psychology , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Psychological Tests
20.
J Neuroimmune Pharmacol ; 7(4): 939-50, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22821377

ABSTRACT

2-chlorodeoxyadenosine (CdA, Cladribine) is an immunosuppressant that has recently been shown to be effective in the treatment of multiple sclerosis (MS). There is extensive clinical experience with CdA for the treatment of neoplastic diseases, especially hematologic malignancies, due to its apoptotic effects on leukemic and several other neoplastic cells. Furthermore, CdA crosses the blood-brain-barrier and thus may also exert its effects directly on cells of the central nervous system (CNS). Therefore, we have studied the effects of CdA on cultured primary rat microglia, the resident macrophage in the CNS, which is also thought to be involved in the pathogenesis of MS. Treatment of microglia with CdA inhibited their proliferation and induced apoptosis. Phosphorylation of CdA to CdATP was required for both effects and was inhibited by deoxycytidine. Furthermore, activation of caspase-3 and -9 revealed the involvement of the intrinsic mitochondrial mediated apoptotic pathway. However, the absence of caspase-8 activation specified independency from the extrinsic death receptor mediated apoptosis. The mitochondrial membrane potential was significantly reduced after CdA exposure and was not conserved with Bax or caspase-3 inhibition. Assessment of DNA fragmentation by TUNEL and DNA-release-assay showed microglia with fragmented nuclei. Other functions of microglia like phagocytosis and LPS-induced NO and TNF-α release were not affected by CdA. These data suggest a potential of CdA treatment to induce not only leukopenia but also apoptosis in microglia in the CNS. These results help to understand the mechanism of action of CdA in CNS diseases and may open the possibility to target microglia.


Subject(s)
Cladribine/pharmacology , Immunosuppressive Agents/pharmacology , Microglia/drug effects , Animals , Animals, Newborn , Apoptosis/drug effects , Blotting, Western , Caspases/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Damage , DNA Fragmentation/drug effects , Membrane Potential, Mitochondrial/drug effects , Membrane Potentials/drug effects , Nitric Oxide/metabolism , Oxazines , Phagocytosis/drug effects , Phosphatidylserines/metabolism , Phosphorylation , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism , Xanthenes
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