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This paper provides up to date prevalence estimates of mental disorders in Germany derived from a national survey (German Health Interview and Examination Survey for Adults, Mental Health Module [DEGS1-MH]). A nationally representative sample (N = 5318) of the adult (18-79) population was examined by clinically trained interviewers with a modified version of the Composite International Diagnostic Interview (DEGS-CIDI) to assess symptoms, syndromes and diagnoses according to DSM-IV-TR (25 diagnoses covered). Of the participants 27.7% met criteria for at least one mental disorder during the past 12 months, among them 44% with more than one disorder and 22% with three or more diagnoses. Most frequent were anxiety (15.3%), mood (9.3%) and substance use disorders (5.7%). Overall rates for mental disorders were substantially higher in women (33% versus 22% in men), younger age group (18-34: 37% versus 20% in age group 65-79), when living without a partner (37% versus 26% with partnership) or with low (38%) versus high socio-economic status (22%). High degree of urbanization (> 500,000 inhabitants versus < 20,000) was associated with elevated rates of psychotic (5.2% versus 2.5%) and mood disorders (13.9% versus 7.8%). The findings confirm that almost one third of the general population is affected by mental disorders and inform about subsets in the population who are particularly affected., (Copyright © 2014 John Wiley & Sons, Ltd.)

For several years, there has been a significant increase of the utilization of health care due to mental disorders in Germany. Epidemiologic studies dealing with the prevalence of mental disorders show that the prevalence of mental disorders haven't increased. In consideration of the relative stable prevalence, currently there are only speculations about the reasons for the increasing service utilization. The capacity of psychiatric-psychosomatic-psychotherapeutic health care services is increasing. Despite the fact that capacity is increasing, in the outpatient and inpatient sector it comes apparent that there is an increasing burden, indicating that the demand for mental health care is not met by the capacity of psychiatric-psychosomatic-psychotherapeutic health care services. Health care provision by general practitioners and somatic disciplines predominate, going along with low cross-disciplinary and coordinated cooperation. So far, cooperative, intersectoral care models for mental disorders have been realized only in individual projects. Valid data are lacking, which need to reveal the causes and especially the consequences of this situation of mental health care provision and provide reference standards for an optimized, need-based care planning. For this reason, it is imperative to advance quality management for the care of mental disorders. With a view to the high rates of somatic comorbidity, an expansion of cooperative forms of mental health care appears essential., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: This study was designed to investigate whether a preventive weight management program (WMP) reduces weight gain during olanzapine (OLZ) treatment. Moreover, we examined the effects of intervention on metabolic parameters., Methods: Patients (N = 100) with schizophrenia or schizoaffective disorder (DSM-IV) who had commenced treatment with OLZ were recruited. Following a run-in period of 4 weeks, 74 patients who had gained at least 1.5 kg body weight were randomized to receive either 12 bi-weekly WMP sessions (prevention group (PG), n = 36), or usual care (control group (CG), n = 38). Anthropometric and metabolic parameters were assessed after the 24-week intervention phase and a 24-week follow-up., Results: Forty-two percent of 74 participants (PG: 36.1%, CG: 47.4%) finished the 24-week intervention phase while 34% of them (PG: 30.6%, CG: 36.8%) completed the 48-week study. There was no significant difference in weight gain between groups (PG: + 3.4 ± 4.2 kg vs. CG: + 4.5 ± 6.1 kg, P = 0.184) after 24 weeks. Nevertheless, PG showed a significantly smaller increase in waist circumference than CG (PG: + 4.6 ± 8.3 cm, CG: + 10.1 ± 7.3 cm, P = 0.019) after 48 weeks. Furthermore, PG showed a significantly smaller increase in fasting glucose (P = 0.031) and 2-h glucose after oral glucose load (P = 0.018) than CG., Conclusions: These results suggest that preventive WMP may reduce the risk of abdominal obesity and deterioration of glucose metabolism in OLZ-treated patients.

Purpose: To advance mental health care use by developing recommendations to increase trust from the general public and patients, those who have been in contact with services, those who have never been in contact and those who care for their families in the mental health care system., Methods: We performed a systematic literature search and the retrieved documents were evaluated by two independent reviewers. Evidence tables were generated and recommendations were developed in an expert and stakeholder consensus process., Results: We developed five recommendations which may increase trust in mental health care services and advance mental health care service utilization., Discussion: Trust is a mutual, complex, multidimensional and dynamic interrelationship of a multitude of factors. Its components may vary between individuals and over time. They may include, among others, age, place of residence, ethnicity, culture, experiences as a service user, and type of disorder. For mental health care services, issues of knowledge about mental health services, confidentiality, continuity of treatment, dignity, safety and avoidance of stigma and coercion are central elements to increase trust., Conclusion: Evidence-based recommendations to increase mutual trust of service users and psychiatrists have been developed and may help to increase mental health care service utilization., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background and Objectives: The German health interview and examination survey for adults (DEGS1) with the mental health module (DEGS1-MH) is the successor to the last survey of mental disorders in the general German population 15 years ago (GHS-MHS). This paper reports the basic findings on the 12-month prevalence of mental disorders, associated disabilities and self-reported healthcare utilization., Methods: A representative national cohort (age range 18-79 years, n = 5,317) was selected and individuals were personally examined (87.5 % face to face and 12.5 % via telephone) by a comprehensive clinical interview using the composite international diagnostic interview (CIDI) questionnaire., Results: The overall 12-month prevalence of mental disorders was 27.7 % with substantial differences between subgroups (e.g. sex, age, socioeconomic status). Mental disorders were found to be particularly impairing (elevated number of disability days). Less than 50 % of those affected reported to be in contact with health services due to mental health problems within the last 12 months (range 10-40 % depending on the number of diagnoses)., Conclusions: Mental disorders were found to be commonplace with a prevalence level comparable to that found in the 1998 predecessor study but several further adjustments will have to be made for a sound methodological comparison between the studies. Apart from individual distress, elevated self-reported disability indicated a high societal disease burden of mental disorders (also in comparison with many somatic diseases). Despite a relatively comprehensive and well developed mental healthcare system in Germany there are still optimisation needs for treatment rates.

The German Association for Psychiatry and Psychotherapy (DGPPN) has committed itself to establish a prospective national cohort of patients with major psychiatric disorders, the so-called DGPPN-Cohort. This project will enable the scientific exploitation of high-quality data and biomaterial from psychiatric patients for research. It will be set up using harmonised data sets and procedures for sample generation and guided by transparent rules for data access and data sharing regarding the central research database. While the main focus lies on biological research, it will be open to all kinds of scientific investigations, including epidemiological, clinical or health-service research.

Background: A discipline- and sector-specific analysis of health-care utilization by persons with mental illness in Germany is an indispensable aid to planning for the provision of adequate basic care., Method: Secondary data from three statutory health insurers and the German Statutory Pension Insurance Scheme for the period 2005-2007 were evaluated to identify insurees with mental illness (ICD-10 diagnosis groups F0-F5)., Results: In the period 2005-2007, 3.28 million (33%) of 9.92 million insurees had at least one contact with the health-care system in which a mental disorder was diagnosed. 50.4% (1,651,367) of these insurees had at least two mental disorders. Nearly all (98.8%) of the insurees with a psychiatric index diagnosis had at least one somatic diagnosis coded as well. 95.7% of treatments were provided in the outpatient setting. Somatic medical specialties provided the majority of treatments both in ambulatory care and in the hospital. For example, 77.5% of persons with severe depression were treated with five kinds of treatment that were provided exclusively by primary care physicians and other specialists in somatic medicine in private practice, sometimes in combination with psychiatric treatment or psychotherapy., Conclusion: There was a high degree of comorbidity of mental and somatic illness. The fact that the vast majority of treatment was provided in the outpatient setting implies that cooperation across health-care sectors and disciplines should be reinforced, and that measures should be taken to ensure the adequate delivery of basic psychiatric care by primary care physicians.

Treatment guidelines provide evidence-based recommendations for diagnosis and treatment to assist clinicians, care givers and patients in finding an optimized treatment option in given clinical situations. Specific treatment guidelines for schizophrenia issued by the German Association of Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and published under the auspices of the Working Group for Scientific Medical Specialist Societies (AWMF) (i.e. fulfilling the highest quality standards at the S3 level) have been available in Germany since 2006. Currently, a comprehensive revision process is ongoing to update these guidelines with the aim to publish the revision before 2014. However, since publication of the German treatment guidelines many clinical trials and meta-analyses have been published which appear to make a new evaluation of antipsychotic drug treatment necessary. Currently available national and international guidelines, such as the WFSBP, PORT and NICE guidelines, place less emphasis on the general superiority of atypical antipsychotic medication but support the idea to evaluate antipsychotic drugs based on the side effect profiles. The present overview discusses the recent guidelines development processes regarding schizophrenia and compares the available German treatment guidelines with recently published international guidelines. Current developments and issues for discussion are described in detail to provide possible implications for changes in treatment recommendations.

In the process of revising ICD-10, the World Health Organization (WHO) has appointed a Working Group on the Classification of Psychotic Disorders (WGPD). Several changes to the classification criteria of schizophrenia and other primary psychotic disorders have been proposed with the aim of increasing the clinical utility, reliability and validity of the diagnostic classification. These proposals will be tested in field trials and subsequently revised according to the needs of clinical practice before final publication in 2015. The main proposals include the following: change of the chapter title, the replacement of the present schizophrenia subtypes with symptom specifiers, a revision of course specifiers, the inclusion of stricter diagnostic criteria for schizoaffective disorder, and a reorganization of acute and transient psychotic disorders and delusional disorders. The proposals for ICD-11 are compared with those for the corresponding DSM-5 chapter., (Copyright © 2013. Published by Elsevier B.V.)

DEGS1-MH is part of the first wave of the German Health Interview and Examination Survey (DEGS1) covering all relevant health issues. Aims of DEGS1-MH are to supplement DEGS1 by describing (1) the distribution and frequency, the severity and the impairments of a wide range of mental disorders, (2) risk factors as well as patterns of help-seeking and health care utilization, and (3) associations between mental and somatic disorders, (4) and by comparisons with a similar survey in the late 1990s (GHS-MHS), longitudinal trends and changes in morbidity over time. Out of all eligible DEGS1 respondents (nationally representative sample aged 18-79), N = 5318 subjects (conditional response rate 88%) were examined at their place of residence by clinically trained interviewers with a modified version of the standardized, computer-assisted Composite International Diagnostic Interview (DEGS-CIDI). Innovative additions were: a comprehensive neuropsychological examination, a broader assessment of psychosis-like experiences, disorder-specific disabilities, help-seeking and health care utilization. The mental health module and its combination with the assessment of somatic and other health issues in DEGS1 allow for internationally unique, detailed and comprehensive analyses about mental disorders and the association of mental and somatic health issues in the community, constituting an improved basis for regular future surveys of this sort., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Valid and feasible quality indicators can measure healthcare quality and show potential for improvement in care. The German Association for Psychiatry and Psychotherapy (DGPPN) has developed trans-sectoral quality indicator sets for four mental disorders with high prevalence (alcohol dependence, dementia, depression and schizophrenia)., Material and Method: The DGPPN followed a structured multistage process and used guideline recommendations and the results of systematic evidence searches as the basis for the development of these quality indicators. This was followed by a structured consensus process for all quality indicators., Results: Four evidence and consensus-based, diagnosis-specific and trans-sectoral quality indicator sets have been developed., Conclusion: It is possible to develop quality indicators on the basis of guideline recommendations. The implementation of the DGPPN quality indicators will play a crucial role in order to evaluate their utility and feasibility as quality measures for German mental healthcare.

Within the efforts to revise ICD-10 and DSM-IV-TR, work groups on the classification of psychotic disorders appointed by the World Health Organization (WHO) and the American Psychiatric Association (APA) have proposed several changes to the corresponding classification criteria of schizophrenia and other psychotic disorders in order to increase the clinical utility, reliability and validity of these diagnoses. These proposed revisions are subject to field trials with the objective of studying whether they will lead to an improvement of the classification systems in comparison to their previous versions. Both a challenge and an opportunity, the APA and WHO have also considered harmonizing between the two classifications. The current status of both suggests that this goal can only be met in part. The main proposed revisions include changes to the number and types of symptoms of schizophrenia, the replacement of existing schizophrenia subtypes with dimensional assessments or symptom specifiers, different modifications of the criteria for schizoaffective disorder, a reorganization of the delusional disorders and the acute and transient psychotic disorders in ICD-11, as well as the revision of course and psychomotor symptoms/catatonia specifiers in both classification systems.

The analysis of the utilization of mental healthcare services using routine data provided by statutory health insurance companies and pension funds is a way to assess the frequency of service use, the distribution of the service use among various healthcare settings (inpatients vs. outpatients, rehabilitation according mainly to the German Social Code Book IX vs. curative treatment according to the German Social Code Book V [note that some elements of rehabilitation are financed according to Social Code Book V as well]) and medical disciplines (psychiatry and psychosomatic medicine vs. somatic disciplines and general medicine). In addition, these data can provide information on the social consequences of mental disorders, as assessed by the number of cases and the duration of sick leave or case numbers of early retirement due to mental disorders. In this study, healthcare utilization data from 10 million Germans were analysed. Within a 3 year observation period (2005-2007), about one-third (approx. 3.3 million) persons had a contact with a healthcare service due to a diagnosis of the ICD-10 groups F0-F5. Given the large number of persons with depression in Germany, the initial results of an analysis of mental healthcare utilization due to depression are presented here. Among the study group of 3.3 million Germans with mental healthcare utilization within the observation period, 1.4 million had at least one contact to healthcare system due to the diagnosis of depression. In most cases, depression was diagnosed without specification of severity. It was found that non-psychiatric disciplines like general practitioners were the most frequently used providers in outpatient mental health care, whereas inpatient treatment predominantly occurred in psychiatric departments. For those persons with depression for which a severity-indicating ICD-10 code was used, it was found that utilization of psychiatric and psychosomatic disciplines increased in both in- and outpatient treatment compared to use of general medical facilities with more severe depression. Specialists for psychosomatic medicine and psychological psychotherapists predominantly treated cases of mild and moderate depression, whereas severe cases were mostly cared for by psychiatrists or psychiatric departments.

Healthcare in Germany is characterized by a dichotomy of a private and a public healthcare sector, which also pertains to mental healthcare. While the prevalence figures of mental disorders in Germany remained fairly constant over the last 15 years, utilization rates of healthcare services due to mental disorders increased by 70-80% including inpatient and outpatient services, sick leave cases and cases of early retirement due to mental disorders. Several challenges are currently evident for mental healthcare in Germany, ranging from interesting a sufficient number of medical students for this field of medicine, dealing with the yet unforeseeable consequences of a novel mental hospital remuneration system, better integration of services and remuneration providers, to elucidating the causes of the increasing utilization rates. Mental healthcare research will take centre stage in addressing these challenges.

Objectives: One of the neurobiological core features of schizophrenic illnesses is a hypo-functionality of the frontal cortex ("cerebral hypofrontality"). The two major classes of antipsychotic medication differ regarding their impact on frontal lobe function and metabolism, with a presumably more positive effect of "atypical" compared to "typical" agents. To date, neurobiological markers reliably predicting the treatment response to different antipsychotics are lacking. The present study, therefore, aimed at establishing a neurophysiological marker of frontal lobe function (NoGo-Anteriorization, NGA) as a predictor of the treatment response to first- and second-generation antipsychotics., Methods: Seventy-six schizophrenic patients were examined three times over a 6-week study period. Patients were treated with first- or second-generation antipsychotics, and NGA, neurocognitive performance, and symptomatology were assessed on admission as well as during two follow-up measurements., Results: Baseline NGA values significantly predicted the treatment response to typical and atypical antipsychotics; however, the direction of this prediction was dependent on the antipsychotic drug regimen. Moreover, atypical antipsychotics had a superior impact on neurocognitive performance and self-reported quality of life., Conclusions: The NGA might be a useful tool in developing individualized treatment strategies based on pathophysiological aspects of schizophrenic illnesses that can be easily determined in clinical routine settings.

The main aim of this guidance of the European Psychiatric Association is to provide evidence-based recommendations on the quality of mental health services in Europe. The recommendations were derived from a systematic search of the best available evidence in the scientific literature, supplemented by information from documents retrieved upon reviewing the identified articles. While most recommendations could be based on empirical studies (although of varying quality), some had to be based on expert opinion alone, but were deemed necessary as well. Another limitation was that the wide variety of service models and service traditions for the mentally ill worldwide often made generalisations difficult. In spite of these limitations, we arrived at 30 recommendations covering structure, process and outcome quality both on a generic and a setting-specific level. Operationalisations for each recommendation with measures to be considered as denominators and numerators are given as well to suggest quality indicators for future benchmarking across European countries. Further pan-European research will need to show whether the implementation of this guidance will lead to improved quality of mental healthcare, and may help to develop useful country-specific cutoffs for the suggested quality indicators., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The stigma of mental illness is a severe burden for people suffering from mental illness both in private and public life, also affecting their relatives, their close social network, and the mental health care system in terms of disciplines, providers, and institutions. Interventions against the stigma of mental illness employ complementary strategies (e.g., protest, education, and contact) and address different target groups (e.g., school children and teachers, journalists, stakeholders). Within this framework, the World Psychiatric Association has adopted an Action Plan with the goal to improve the image of psychiatry and to reduce potential stigmatizing attitudes toward psychiatry and psychiatrists. To evaluate such interventions, a questionnaire has been developed that assesses opinions and attitudes toward psychiatrists and psychiatry in different samples of medical specialists (psychiatrists and general practitioners). The questionnaire comprises scales about perceived stigma in terms of the perception of societal stereotypes, self-stigma in terms of stereotype agreement, perceived stigma in terms of structural discriminations, discrimination experiences, stigma outcomes, and attitudes toward a second medical discipline. It is available in several languages (Arab, English, German, Japanese, Polish, and Spanish) and can easily be adapted for utilization in other medical specialties.

In August 2002 the Japanese Society of Psychiatry and Neurology decided to rename the Japanese expression for schizophrenia from Sêshin Bunretsu Byô to Tôgô Shicchô Shô. Currently the psychiatric classification systems ICD-10 and DSM-IV are under revision. Against this background the Japanese process of renaming a psychiatric disorder is of high interest as far as the clinical, social and cultural implications of the new name are concerned.The authors give an overview of the Japanese process of renaming schizophrenia. Its background and realization are explained and the expectations of Japanese physicians, patients and their families related to the new name are analysed. Furthermore, its effects are evaluated. The aim of the paper is to clarify in how far the Japanese example may serve as a model for evaluating the possible implications that a renaming or nosological redefinition of schizophrenia might have in the course of the revision process of ICD 10 and DSM IV.

Integrative models of the etiopathogesnesis of psychotic disorders are needed since a wealth of information from such diverse fields as neurobiology, psychology, and the social sciences is currently changing the concepts of mental disorders. Several approaches to integrate these streams of information into coherent concepts of psychosis are feasible and will need to be assessed in future experimental studies. Common to these concepts are the notion of psychotic disorders as brain disorders and a polythetic approach in that it is increasingly realized that a multitude of interindividually partially different pathogenetic factors interact in individual persons in a complex fashion resulting in the clinical symptoms of psychosis.

Objectives: The pathophysiology of mental disorders is largely unresolved. We propose that the identification of abnormalities in brain modular networks will provide a promising approach for the understanding of mental disorders., Methods: We review the current discussion on the neuroscientific basis of psychiatric diseases and review recent studies in functional neuroimaging and systems physiology on mental functions of the human brain., Results: We propose that brain functional units are organized in modular networks. Modular networks allow for flexibility within the modular processing units and across interconnected modules affording optimization of task performance and deficit compensation in disease. As an example it will be shown that differentiated modules in medial frontal cortex play a critical role for the control of behaviour. This will be contrasted to recent studies in neurological and psychiatric patients revealing behavioural abnormalities due to lesions or reversibly deprived functions in the medial frontal cortex., Conclusions: These findings are conceptualized as starting points for a neuroscience based diagnosis and treatment of brain diseases at the border of psychiatry and neurology., (© 2011 Informa Healthcare)

We performed an Internet-based questionnaire survey of the opinions of German-speaking psychiatrists regarding the experiences with the 10th revision of the international classification of mental disorders (chapter F of ICD-10). We received 304 completed questionnaires including more than 500 free-text comments. The responding group was characterized by professionally experienced middle-aged psychiatrists. German-speaking psychiatrists were comparatively content with ICD-10. Most diagnostic categories received a "satisfied" or "very satisfied" rating by the majority of respondents. Negative "goodness of fit" ratings--a possible indicator of the need for revision--were not higher than 50% for any category. Based on free-text entries, neurasthenia was the single diagnostic category most often suggested for deletion in ICD-11. Changes were considered necessary mainly for dementias and personality disorders. Adult attention deficit disorder and narcissistic personality disorder were the two diagnostic categories most frequently suggested to be added as new categories. This study provides valuable information related to perceived clinical utility of the classification, though with a narrow sample. Information about clinicians' experiences should be combined with scientific evidence for the revision process of ICD-11., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Purpose of Review: The German mental healthcare system is currently undergoing discussions regarding the assessment of mental healthcare quality and the identification of potentials for optimizing mental healthcare. Quality assurance projects play an important role in the optimization of the care for the mentally ill in Germany. This review describes the most recent results of quality assurance programs from Germany as identified by a systematic literature search covering the time span 1 January 2008 until 1 June 2009., Recent Findings: The German mental healthcare system is characterized by a high degree of structural quality. Quality assurance research in German mental healthcare is multifaceted and several projects are underway to determine the cost-effectiveness of procedures in mental healthcare and the development of quality indicators., Summary: In Germany, mental healthcare research is a rapidly developing field. Potentials for improvements can be identified in the assessment of process and outcome quality, the regional distribution, and the coordination among service providers. More studies are needed to identify the best methods to assess quality in mental healthcare with a view to improve process and outcome quality.

Reclassifying psychotic disorders in the upcoming revisions of the mental disorders section of ICD-10 and DSM-IV will first necessitate the development of a unified and operationalized definition of the term "psychosis". Ideally, such a definition would be harmonized between both groups of diagnostic classification systems and become part of a glossary of terms. Conceptually and based on epidemiological and some genetic work, incorporating dimensional criteria and criteria for prodromal high-risk symptoms may become feasible. Considering the currently available evidence from genetic, neuroimaging and neurophysiological studies, none seems yet sufficiently validated to warrant major changes. However, further research in these areas promises to yield important new insights which may become relevant for the classification of psychotic disorders in the near future. Given the rapid progress in these fields, regular updates of the classification criteria at shorter intervals than in the past may become necessary.

Objective: The study objective is to evaluate the use of qEEG data for the cross-sectional differentiation of mild cognitive impairment (MCI) from mild Alzheimer's disease (AD) and in the longitudinal prediction of cognitive decline in MCI., Methods: Eighty-eight subjects with MCI and 42 subjects with mild probable AD were enrolled. Baseline EEGs were recorded using a 32-channel system with electrode positioning according to the international 10-20 system. Digitalized EEG data were further studied by quantitative spectral analysis. Study subjects were followed up for 1 year and reassessed psychometrically. An increase of the total ADAS-cog score of >or= 4 points was regarded as a significant cognitive decline. Using this cut-off, MCI subjects were sub-grouped into stable MCI (s-MCI) and progressing MCI (p-MCI)., Results: AD subjects and p-MCI subjects were differentiated from s-MCI subjects by a reduction of alpha power over posterior leads. Reduction of alpha power and mean frequency were significantly correlated with poorer cognitive performance in psychometric tests. Baseline values of alpha power over posterior leads had the highest positive predictive power for MCI and AD (69-80%) and predicted cognitive decline in MCI within a 1-year follow up., Conclusions: qEEG revealed decreased alpha activity in progressing MCI and mild AD prior to an increase of slow wave activity, which typically occurs in advancing AD. This finding may reflect an affection of thalamo-cortical relay activity and cortical connectivity in the early disease course of AD. Reduced alpha activity in MCI subjects at baseline may have prognostic value regarding future cognitive decline., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

We propose to use modules representing functional subunits of the brain as the substrates of pathogenetic factors in mental disorders. This approach is based on scientific evidence from neurophysiology and cognitive psychology regarding the organisation of the human brain in functionally discernible, not necessarily temporally or spatially stable subunits, which are interconnected in complex, often multilayered networks of neuronal circuits. Such a definition would reconcile modern network theories of brain function with localizationist models. Module-based diagnosis and therapy of mental disorders will be the goal of a modular psychiatry, which has the advantage that it is founded in neuroscientific evidence and does not rely on arbitrary definitions of mental disorders based mainly on clinical empiricism.

The revision process of the international psychiatric classification systems has started and is expected to result in new versions of the International Classification of Disorders (then ICD-11) and the Diagnostic and Statistical Manual (then DSM-V) in approximately 2014 and 2012, respectively. In the process of developing DSM-V, several research conferences jointly sponsored by the American Psychiatric Association, the National Institutes of Health, and the World Health Organization, are currently taking place. We will here focus on the impact that the DSM-V initiative "Deconstructing Psychosis" will have on the future of diagnosing a psychotic state, and how this may be viewed from a European context of Kraepelin's nosology of psychiatric disorders.

A case of asystole (> 5 s) during electroconvulsive therapy (ECT) is reported in a patient who was subsequently diagnosed to have Brugada syndrome (BS). This hereditary sodium-channelopathy is characterized by typical, though intermittent, ECG abnormalities and carries a high risk of ventricular arrythmia and sudden cardiac death. The general occurence of BS is rare; however, it is more prevalent in men and in southeast Asian populations. As in the reported case, BS carriers may lack a telltale medical history and can present with normal ECG recordings. In these cases, BS can only be unmasked by repeated ECG recordings over time or by specialist cardiological examinations. To our knowledge, BS, which was first characterized in 1992, has not yet been in the focus of cardiac complications during ECT. However, as the presented case illustrates, this syndrome should be considered as a rare but potentially severe cardiac risk factor in the context of ECT.

In common parlance, the close relationship between the heart and the mind is well known. Epidemiologic investigations of the last 20 years have put this relationship on an empirically confirmed basis: patients with heart disease, especially coronary artery disease, suffer from major depression at a rate exceeding chance alone. The reasons are still unknown, but current hypotheses focus on the influence of depression on endothelial function, blood coagulation, cardiac arrhythmias, inflammatory reactions, and lifestyle factors. Major depression worsens the prognosis of cardiologic disorders. Depression in patients with heart disease must be treated equally vigorously as in patients without heart disease. In patients with coronary artery disease and depression, only few controlled clinical studies are available, but have shown that selective serotonin reuptake inhibitors are effective and safe. They are therefore currently the drugs of choice. It is important for the clinician to consider major and minor depression in the differential diagnosis of psychiatric and somatic symptoms in patients with heart disease, to diagnose depression without delay, and promptly initiate an appropriate therapy according to current treatment guidelines.

Missense mutations in 22 genes account for one-quarter of Charcot-Marie-Tooth (CMT) hereditary neuropathies. Myelin Protein Zero (MPZ, P0) mutations produce phenotypes ranging from adult demyelinating (CMT1B) to early onset [Déjérine-Sottas syndrome (DSS) or congenital hypomyelination] to predominantly axonal neuropathy, suggesting gain of function mechanisms. To test this directly, we produced mice in which either the MpzS63C (DSS) or MpzS63del (CMT1B) transgene was inserted randomly, so that the endogenous Mpz alleles could compensate for any loss of mutant P0 function. We show that either mutant allele produces demyelinating neuropathy that mimics the corresponding human disease. However, P0S63C creates a packing defect in the myelin sheath, whereas P0S63del does not arrive to the myelin sheath and is instead retained in the endoplasmic reticulum, where it elicits an unfolded protein response (UPR). This is the first evidence for UPR in association with neuropathy and provides a model to determine whether and how mutant proteins can provoke demyelination from outside of myelin.

Disturbance of prefrontal brain functions is assumed to be responsible for prominent psychopathological symptoms in psychotic disorders. Treatment with atypical, in contrast to typical antipsychotics is considered as a possible strategy for an improvement of prefrontal brain function. In the present study, response control as a specific prefrontal brain function was assessed by means of the Nogo-anteriorization (NGA) derived from the event-related potentials elicited during a Go-NoGo task in a consecutive sample of 39 patients suffering from acute psychotic disorders (brief psychotic disorders, 298.8, n = 34 and schizoaffective disorders, 295.70, n = 5; cycloid psychoses according to the Leonhard classification). A highly significant positive correlation between the amount of antipsychotic medication in terms of chlorpromazine equivalents per day and the NGA as a measure of prefrontal response control was only found in the subgroup of patients treated exclusively or predominantly with atypical antipsychotics but not for those treated with typical antipsychotics. These results are in line with the notion that atypical antipsychotics may exert a beneficial effect on prefrontal brain function.

We investigated the function of the anterior cingulate cortex (ACC) with the continuous performance test (CPT) in patients with chronic schizophrenias. We had previously shown that the NoGo anteriorisation (NGA), which consists of a more anterior center of gravity (centroid) of the event-related potentials during the inhibition of a prepared motor response, correlates with physiological activation of the ACC in healthy probands. However, in patients with schizophrenias, the event-related potentials are located more anteriorly in the Go condition and more posteriorly in the NoGo condition, which leads to a decreased NGA reflecting reduced activation of the ACC. We now extend our observations to a larger number of patients with different subgroups of chronic schizophrenias according to Leonhard's classification system. While the schizophrenic patients as a group showed only a trend towards a decreased NGA, there was a significant reduction of the NGA in patients with systematic schizophrenias but not in those with unsystematic schizophrenias. Our results show that a subclassification of "schizophrenic" patients is useful to detect differences between subgroups, which may reflect differences in pathophysiology.

Objective: Prefrontal structures such as the anterior cingulate cortex (ACC) play a decisive role in processes of action monitoring and response control, functions often impaired in schizophrenia. Patients with cycloid psychoses exhibit some characteristic neurophysiological features not indicative of the cerebral hypofrontality observed in schizophrenia. This study aimed at examining if cycloid psychoses-unlike schizophrenias-involve a normal brain-electrical topography during a task demanding prefrontal response control., Methods: Thirty-seven patients with cycloid psychoses and 37 healthy controls were investigated electrophysiologically while performing a Continuous Performance Test (CPT). Topographical analyses were conducted to individually quantify the Nogo-anteriorisation (NGA) as a neurophysiological index of prefrontal response control., Results: The patients exhibited an unaltered topography with a mean NGA not significantly different from the controls. They did, however, differ from the control group regarding their Global Field Power (GFP), with a significantly reduced GFP (p<0.001) and decreased latencies (p<0.01) during Nogo trials. On a behavioral level, patients exhibited prolonged reaction times and an increased rate of omission errors., Conclusions: The investigated patients showed an activation of specific (presumably frontal) brain areas during Nogo trials, resulting in a frontalisation of the brain-electrical field comparable to the control group. However, the strength of this activation was apparently reduced. The patients' unaltered topographical pattern contrasts with previous findings in schizophrenic patients and supports the hypothesis that cycloid psychoses entail less severe prefrontal deficits than schizophrenias, which might be an indication of different biological backgrounds for both groups of endogenous psychoses.

Mice with a targeted deletion of the cytokine-inducible nitric oxide synthase gene (iNOS(-/-)) show increased severity of experimental autoimmune encephalomyelitis (EAE). We studied the mechanisms of susceptibility to myelin-basic protein-induced 'active' EAE in iNOS(-/-) mice. Spleen cells and lymph node cells from iNOS(-/-) mice with EAE showed a significantly enhanced ex vivo proliferation and production of T-helper 1 (Th1) cytokines (interferon-gamma by 157 and 57% and tumor-necrosis-factor-alpha by 86 and 27%, respectively). We conclude that NO produced by iNOS plays a protective role in EAE probably by inhibiting the production of Th1 cytokines and T cell proliferation.

The anterior cingulate cortex (ACC) is a key region within the human prefrontal cortex that has been shown to be dysfunctional in schizophrenic patients. Supporting evidence for this notion has been collected with neuroimaging methods during various cognitive activation tasks. Recently, electrophysiological ACC activity has been demonstrated by means of a three-dimensional source location with low resolution electromagnetic tomography (LORETA) in the event-related potentials elicited during the NoGo condition of the Continuous Performance Test (CPT) as compared to its Go condition. Thirty-one schizophrenic patients and 31 age- and gender-matched healthy volunteers were investigated with this newly developed electrophysiological method. LORETA analysis revealed a significantly diminished brain electrical activity in the ACC of schizophrenic patients as compared to controls during the NoGo condition of the CPT. This result supports the assumption of a functional deficit of the ACC during this cognitive task as a central feature in schizophrenias and, thereby, specifies the general concept of hypofrontality. Moreover, this investigation underscores the value of sophisticated electrophysiological methods in combination with unambiguously designed mental tasks for the evaluation of the pathophysiological processes underlying schizophrenic diseases.

The pathogenic role of nitric oxide (NO) in multiple sclerosis (MS) remains controversial. Some groups have reported a pathogenic role of NO in experimental autoimmune encephalomyelitis (EAE), an animal model of some aspects of MS, whereas we and others have found a disease-suppressive effect of NO in EAE. Because the previously used EAE models have a mainly monophasic inflammatory disease course, distinct from MS, we here studied EAE in the DA rat, which better models the demyelinating and relapsing disease course of human MS. The induction of EAE in DA rats led to 1) severe inflammatory infiltrates mainly in the lumbar spinal cord; 2) an up-regulation of the activity of the cytokine-inducible isoform of NO synthases (NOS-II); and 3) increased tissue protein tyrosine nitration, as indicated by peroxynitrite (ONOO(-)), as a marker of nitrosative stress. Sources of superoxide metabolism, i.e., NADPH oxidase, myeloperoxidase, and superoxide dismutase, remained unchanged. Early treatment of animals with aminoguanidine, a relatively selective inhibitor of NOS-II, lowered nitrotyrosine immunoreactivity but at the same time led to more severe disease and pronounced inflammatory infiltrates in the lumbar spinal cord. Our results suggest a rather protective role of NOS-II induction and nitrosative stress in EAE in DA rats and support the hypothesis of a disease-mitigating immunomodulatory role of NO in this animal model of MS., (Copyright 2003 Wiley-Liss, Inc.)

Mice deficient in the peripheral myelin component P0 mimic severe forms of inherited peripheral neuropathies in humans, with defective myelin formation and consequent axonal loss. We cross-bred these mice with the spontaneous mutant C57BL/Wld(s) typically showing protection from Wallerian degeneration because of fusion of the ubiquitination factor E4B (Ube4b) and nicotinamide mononucleotide adenylyltransferase (Nmnat) genes. We found that in the double mutants, the robust myelin-related axonal loss is reduced at 6 weeks and 3 months of age. Moreover, retrograde labeling from plantar nerves revealed an increased survival of motor axons. These motor axons appeared functionally active because both the amplitude of compound muscle action potentials and muscle strength were less reduced in the double mutants. At 6 months of age, reduction of axonal loss was no longer detectable in the double mutants when compared with littermates carrying the P0 null mutation only, although the Wld(s) gene was not reduced in its expression at this age. We conclude that myelin-related axonal loss is a process having some features in common with Wallerian degeneration. Introducing the Wld(s) gene would be a promising approach to delaying detrimental axonal loss in myelin disorders.

Olfactory reference syndrome (ORS) is a rare psychiatric condition characterized by isolated olfactory hallucinations or illusionary misinterpretations of odours with delusional self-reference and a typical contrite reaction. The aetiopathology of the disorder is unclear. Three cases of ORS are presented, which show the typical clinical symptom constellation, while pointing to various underlying psychiatric illnesses and differing treatment responses. Nosological aspects are discussed on the basis of the available literature.

Inherited demyelinating neuropathies are chronically disabling human disorders caused by various genetic defects, including deletions, single site mutations, and duplications in the respective myelin genes. We have shown in a mouse model of one distinct hereditary demyelinating neuropathy (heterozygous P0-deficiency, P0+-) that an additional null mutation in the recombination activating gene-1 (RAG-1--) leads to a substantially milder disorder, indicating a disease modifying role of T-lymphocytes. In the present study, we addressed the role of lymphocytes in the mouse model by reconstituting bone marrow of P0+-/RAG-1-- mice with bone marrow from immunocompetent wild-type mice. We compared the pathology and nerve conduction in double mutant mice (P0+-/RAG-1-- on a C57BL/6 background) with that in double mutants after receiving a bone marrow transplant. We found that the milder demyelination seen in the lymphocyte-deficient P0+-/RAG-1-- mutants was reverted to the more severe pathology by reestablishing a competent immune system by bone marrow transfer. These data corroborate the concept that the immune system contributes substantially to the pathologic process in this mouse model and may open new avenues to ameliorate human hereditary neuropathies by exploiting immunosuppressive treatments., (Copyright 2001 Academic Press.)

Objective: To test the hypothesis that different preceding infections influence the neurophysiologic classification and clinical features of Guillain-Barré syndrome (GBS)., Methods: We tested pretreatment sera, 7 +/- 3 (mean +/- SD) days from onset, from 229 patients with GBS in a multicenter trial of plasma exchange and immunoglobulin, for serological markers of infection, adhesion molecules, and cytokine receptors, and compared these with neurophysiologic and clinical features., Results: Recent infection by Campylobacter jejuni was found in 53 patients (23%), cytomegalovirus in 19 (8%), and Epstein-Barr virus in four (2%). Patients with C. jejuni infection were more likely than others to have neurophysiologic criteria of axonal neuropathy or inexcitable nerves, antiganglioside GM(1) antibodies, pure motor GBS, lower CSF protein, and worse outcome. Patients with cytomegalovirus infection were younger and more likely than others to have raised serum concentrations of molecules important in T lymphocyte activation and migration, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte selectin, and soluble interleukin-2 receptor (sIL-2R). Concentrations of sICAM-1 and soluble tumor necrosis factor receptor were higher in patients with inexcitable nerves than those with demyelinating neurophysiology. Logistic regression analysis showed death or inability to walk unaided at 48 weeks were associated with diarrhea, inexcitable nerves, severe arm weakness, age over 50, raised sIL-2R concentration and absence of immunoglobulin (Ig) M antiganglioside GM(1) antibodies., Conclusions: Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features. A single infectious agent caused more than one type of pathology in GBS, implying interaction with additional host factors. Most patients had no identified infection.

The purpose of this study was to further characterize neuromyotonia in mice with deletions and point mutations of myelin protein genes. Clinical observation showed irregular stretching of the hindlimbs, tremor and generalized myokymia in mice with targeted deletions of the genes encoding myelin protein zero (P0-/-) or peripheral myelin protein 22 (Pmp22-/-), and Trembler mice, which carry a point mutation of Pmp22. By electromyography (EMG), we found irregular high-frequency bursts of spontaneous motor unit activity and rhythmic doublet or multiplet discharges of motor units in these mouse models of human hereditary neuropathies. The EMG signs are typical for neuromyotonia and myokymia, respectively. The activity persisted after a proximal nerve section in many cases, localizing the generator to the peripheral nerve or the muscle. We now show that blocking neuromuscular transmission with suxamethonium abolished the spontaneous activity, ruling out a muscle origin. Phenytoin ameliorated the motor behavior. Taken together, our study shows that neuromyotonia develops in different mouse models of hereditary myelinopathies. This indicates that spontaneous motor unit activity may underlie neuromyotonia, which is occasionally observed in Charcot-Marie-Tooth disease. These animal models will be useful to study the pathogenesis of neuromyotonia., (Copyright 2000 John Wiley & Sons, Inc.)