WFS1 variants in Finnish patients with diabetes mellitus, sensorineural hearing impairment or optic atrophy, and in suicide victims.

Mutations in the wolframin gene, WFS1, cause Wolfram syndrome, a rare recessive neurodegenerative disorder. The clinical features include early-onset bilateral optic atrophy (OA), diabetes mellitus (DM), diabetes insipidus, hearing impairment, urinary tract abnormalities and psychiatric illness, and, furthermore, WFS1 variants appear to be associated with non-syndromic DM and hearing impairment. Variation of WFS1 was investigated in Finnish subjects consisting 182 patients with DM, 117 patients with sensorineural hearing impairment (SNHI) and 44 patients with OA, and in 95 suicide victims. Twenty-two variants were found in the coding region of WFS1, including three novel nonsynonymous variants. The frequency of the p.[His456] allele was significantly higher in the patients with SNHI (11.5%; corrected P=0.00008), DM (6.6%; corrected P=0.036) or OA (9.1%; corrected P=0.043) than that in the 285 controls (3.3%). The frequency of the p.[His611] allele was 55.8% in the patients with DM being higher than that in the controls (47%; corrected P=0.039). The frequencies of p.[His456] and p.[His611] were similarly increased in an independent group of patients with DM (N=299). The results support previous findings that genetic variation of WFS1 contributes to the risk of DM and SNHI.

Cavum septum pellucidum and psychopathy.

The presence of cavum septum pellucidum (CSP) has been reported to be a neurodevelopmental marker of psychopathy. We scanned 26 violent offenders and 25 controls; 2 offenders and 2 controls had CSP (8% in both groups). Thus, the presence of CSP is not a common or a unique feature of antisocial personality disorder or psychopathy.

Collagen XVII: a shared antigen in neurodermatological interactions?

Collagen XVII is a nonfibril-forming transmembrane collagen, which functions as both a matrix protein and a cell-surface receptor. It is particularly copious in the skin, where it is known to be a structural component of hemidesmosomes. In addition, collagen XVII has been found to be present in the central nervous system, thus offering an explanation for the statistical association between bullous pemphigoid, in which autoimmunity is directed against dermal collagen XVII, and neurological diseases. In support of the hypothesis that collagen XVII serves as a shared antigen mediating an immune response between skin and brain, research on animal and human tissue, as well as numerous epidemiological and case studies, is presented.

Factors Affecting Treatment Regress and Progress in Forensic Psychiatry: A Thematic Analysis.

International variability and shifting trends in forensic psychiatry lead to gaps in national service provision and needs for service development. This study explores these needs through the subjective narratives of those involved in Finnish forensic services, either as forensic psychiatric patients, their parents, or service providers. Data was gathered by means of thematic interview and subjected to thematic analysis. Three main themes emerged: (1) pre-treatment challenges, (2) institutional/treatment-related concerns about therapeutic security and (3) adapting and recovery. The research highlights the need to develop forensic psychiatric services at three levels. First, it calls for increased risk awareness and risk assessment skills at the general psychiatric level. Second, it emphasizes the need for increased therapeutic engagement throughout the rehabilitative process. Third, it calls for structured and meaningful post-discharge aftercare. At all three levels, gradated security-aware standardization and patient triage in forensic services would help to develop and maintain an intact care pathway. This would decrease offending, marginalization, and suffering. Only then can we begin to meet the requirements of the WHO European Mental Health Action Plan. These findings can contribute to the development of international, standardized treatment models for clinical forensic psychiatric practices.

Forensic psychiatry in Finland: an overview of past, present and future.

Despite a recent contrary trend, Finland has been for decades one of the most violent countries in Western Europe. Also, Finland has had one of the highest number of psychiatric beds per capita in Europe, although this, too, has seen a sharp decline. Against this background, among other national idiosyncrasies, Finland has developed its forensic psychiatric services. Here, we describe the legal, organizational and clinical structure of these services, and outline the historical and current issues that have shaped them. Finally, we consider future challenges facing the Finnish forensic service system, as part of wider European and global trends.

Offense-Related Issues in Forensic Psychiatric Treatment: A Thematic Analysis.

Characteristics unique to forensic psychiatric treatment include coming to terms with the offenses committed, the long duration of treatment and the assessment of the risk of repeat offending. This study describes the views of both patients and staff on the significance of the patient's offense as a part of forensic psychiatric rehabilitation. Eight forensic psychiatric patients and eight forensic psychiatric nurses from two forensic psychiatric hospitals in Finland participated in this study. Data were gathered by means of thematic interview and analyzed by means of thematic analysis. The findings suggest that patients and professionals alike concur that ascertaining the factors with a bearing on the offense, and working through the offense and the factors leading up to it, constitute an essential aspect of forensic treatment. This, in turn, has a bearing on the planning and administration of a treatment plan consisting of both medical and psychosocial support and interventions intended to enable patients to live independent, fulfilling lives, thus reducing the likelihood of reoffending. The findings of this study can be used as part of the development of international, standardized treatment models for clinical forensic psychiatric practices.

External factors influencing length of stay in forensic services - a European evaluation. / Czynniki zewnetrzne wplywajace na dlugosc pobytu w osrodkach psychiatrii sadowej ­ badanie europejskie.

OBJECTIVES: A growing number of patients whose length-of-stay in forensic services is aboveaverage length are identifiable in several European countries. Forensic services are situated within a particular sociocultural setting. Accordingly, this trend to increased admission length cannot be solely attributed to patient characteristics. This is the first known study exploring the influence of external factors on length-of-stay in forensic services. METHODS: Representatives from 16 European countries, members of the international COST project, focused on forensic psychiatric service, analyzed their respective forensic services using a structured tool. Responses were combined and analyzed using thematic analysis. RESULTS: Four themes described the factors influencing length-of-stay: care and treatment pathways; resources; legal and systemic impact; and sharing expertise. CONCLUSIONS: Findings suggest multidisciplinary consideration of the whole care pathway is required to address increased length-of-stay. Further research is required to support development of evidence-based standards applicable across Europe, and improve outcomes for patients at risk of increased length-of-stay in forensic services.

Modern forensic psychiatric hospital design: clinical, legal and structural aspects.

Forensic psychiatric care must be provided within the least restrictive setting possible, whilst simultaneously maintaining appropriate levels of security. This presents particular challenges for the design of forensic psychiatric hospitals, which are required to provide both a therapeutic and a safe material environment, often for extended periods of treatment and rehabilitation. By taking into consideration variable trends in psychiatric service provision and myriad clinical, legal and ethical issues, interdisciplinary forensic facility design teams are at the very forefront in implementing the latest developments in medical architecture. Also, although there are significant differences in how forensic psychiatric services are organized around the world, the underlying clinical challenges and increasingly research-based treatment principles are similar worldwide; it is therefore becoming less acceptable to operate and develop national forensic services without reference to international standards. Accordingly, we here review the literature on what features of forensic psychiatric facilities best serve the needs of those patients who need to rely on them, and we present a systematic and widely applicable approach to the complex and costly challenge of modern forensic psychiatric hospital design.

European Psychiatric Association (EPA) guidance on forensic psychiatry: Evidence based assessment and treatment of mentally disordered offenders.

Forensic psychiatry in Europe is a specialty primarily concerned with individuals who have either offended or present a risk of doing so, and who also suffer from a psychiatric condition. These mentally disordered offenders (MDOs) are often cared for in secure psychiatric environments or prisons. In this guidance paper we first present an overview of the field of forensic psychiatry from a European perspective. We then present a review of the literature summarising the evidence on the assessment and treatment of MDOs under the following headings: The forensic psychiatrist as expert witness, risk, treatment settings for mentally disordered offenders, and what works for MDOs. We undertook a rapid review of the literature with search terms related to: forensic psychiatry, review articles, randomised controlled trials and best practice. We searched the Medline, Embase, PsycINFO, and Cochrane library databases from 2000 onwards for adult groups only. We scrutinised publications for additional relevant literature, and searched the websites of relevant professional organisations for policies, statements or guidance of interest. We present the findings of the scientific literature as well as recommendations for best practice drawing additionally from the guidance documents identified. We found that the evidence base for forensic-psychiatric practice is weak though there is some evidence to suggest that psychiatric care produces better outcomes than criminal justice detention only. Practitioners need to follow general psychiatric guidance as well as that for offenders, adapted for the complex needs of this patient group, paying particular attention to long-term detention and ethical issues.

Distribution of collagen XVII in the human brain.

We have recently discovered collagen XVII to be present in neurons of the human central nervous system. Collagen XVII has previously been primarily studied in the field of dermatopathology since it is abundantly expressed in the skin, which, like the nervous system, is ectodermal in origin. A link between dermatopathological and neurological entities has been implied due to clinical case studies revealing an association between bullous pemphigoid and age-related neurodegenerative disorders. The objective of this study was to assess the distribution of collagen XVII in the human brain in relation to normal ageing. Post-mortem brain tissue was obtained from 11 neurologically unimpaired subjects who had died from cardiovascular causes at the age of 17 to 78 years. Collagen XVII expression in various neuroanatomical regions, representing essentially the entire human brain, was then assessed using immunohistochemistry. We found collagen XVII to be expressed widely in the brain and to be located primarily in the soma and proximal axons of neurons. In contrast, glial cells did not express collagen XVII. The expression varied strikingly between different neuroanatomical regions, being most notable in motor nuclei and Betz cells followed by pyramidal neurons. There was no correlation between collagen XVII expression and variables such as gender, age at death, post-mortem delay and fixation time whereas a mode of death leading to notable neuronal ischemia depleted the protein expression. Many neurodegenerative disorders display a specific pattern of neuroanatomical involvement, thus the regionally variable expression of collagen XVII offers new prospects for research.

Meeting Report of the Pathogenesis of Pemphigus and Pemphigoid Meeting in Munich, September 2016.

Autoimmune blistering diseases are a heterogeneous group of about a dozen complex disorders that are characterized by intraepidermal (pemphigus) and subepidermal blistering (pemphigoid diseases and dermatitis herpetiformis). The Pathogenesis of Pemphigus and Pemphigoid Meeting, organized by the Departments of Dermatology in Lübeck and Marburg and the Institute of Anatomy and Cell Biology, Munich, was held in September 2016 in Munich. The meeting brought together basic scientists and clinicians from all continents dedicating their work to autoimmune blistering diseases. Considerable advances have been made in describing incidences and prevalences of these diseases and linking comorbidities with autoantibody reactivities and clinical variants, for example, dipeptidyl peptidase-IV inhibitor-associated noninflammatory bullous pemphigoid. Although new entities are still being described, diagnosis of most autoimmune blistering diseases can now be achieved using standardized and widely available serological test systems. Various experimental mouse models of pemphigus and pemphigoid disease are increasingly being used to understand mechanisms of central and peripheral tolerance and to evaluate more specific treatment approaches for these disorders, such as molecules that target autoreactive T and B cells and anti-inflammatory mediators, that is, dimethyl fumarate, phosphodiesterase 4, and leukotriene B4 inhibitors in pemphigoid disorders, and chimeric antigen receptor T cells in pemphigus. Very recent experimental data about the immunopathology and the determinants of autoantibody formation and keratinocyte susceptibility in pemphigus were discussed. With regard to cellular mechanisms leading to the loss of cell-cell adhesion, new ideas were shared in the field of signal transduction. Major steps were taken to put the various partly contradictory and controversial findings about the effects of pemphigus autoantibodies and other inflammatory mediators into perspective and broaden our view of the complex pathophysiology of this disease. Finally, two investigator-initiated multicenter trials highlighted doxycycline and dapsone as valuable medications in the treatment of bullous pemphigoid.

Collagen XVII is expressed in human CNS neurons.

Type XVII collagen (collagen XVII) is a component of hemidesmosomes, which connect epithelial cells to the underlying basement membrane. Previously, an association has been suggested between neurological disorders and the skin disease bullous pemphigoid, where autoimmunity is directed against collagen XVII. Furthermore, the lack of alpha6 integrin, a ligand of collagen XVII, has been implicated in defects of cortical organization in the mouse brain. In this study, we demonstrate for the first time the presence of collagen XVII in neurons of the human brain by in situ hybridisation, immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). We propose that collagen XVII may be involved in the pathogenesis of various disorders affecting neuronal migration or synaptic plasticity.

Psychiatric and neurological disorders are associated with bullous pemphigoid - a nationwide Finnish Care Register study.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease with increasing incidence. BP is associated with neurological disorders, but it has not been established, what subtypes of dementia and stroke are associated with BP, and what is the temporal relation between these diseases. Also, the association between BP and psychiatric disorders is controversial. We conducted a retrospective nationwide study, using the Finnish Care Register for Health Care diagnoses between 1987 and 2013. The study population of 4524 BP patients were compared with 66138 patients with basocellular carcinoma (BCC), neurological and psychiatric comorbid disorders were evaluated for both groups, and associations were estimated by Cox regression and logistic regression analyses. The strongest risk of developing BP was found after diagnosis of multiple sclerosis (MS) (OR=5.9, 95% CI 3.9-8.5). Among psychiatric diseases, the corresponding risk was strongest in schizophrenia (OR=2.7, 95% CI 2.0-3.5), and as a novel finding, also personality disorders (OR=2.2, 95% CI 1.3-3.3) preceded BP. In conclusion, many psychiatric disorders, especially schizophrenia, carry heightened risk for BP. Furthermore, several neurological diseases which cause central nervous system inflammation or degeneration were related to BP, and the association was strongest between MS and BP.

Developing forensic mental healthcare in kosovo.

In many economically struggling societies, forensic psychiatry is still in its initial developmental stages and thus forensic patients pose an ongoing challenge for the healthcare and juridical systems. In this article, we present the various issues and problems that arose when establishing the first forensic psychiatric institute in Kosovo - a country whose population has constantly been reported as suffering from a high psychiatric morbidity due to long-lasting traumatic experiences during the war of 1999. The implementation of a new forensic psychiatric institute in the developing mental healthcare system of Kosovo, still characterized by considerable shortages, required substantial effort on various levels. On the policy and financial level, it was made possible by a clear intent and coordinated commitment of all responsible national stakeholders and authorities, such as the Ministries of Health and Justice, and by the financial contribution of the European Commission. Most decisive in terms of the success of the project was capacity building in human resources, i.e., the recruitment and training of motivated staff. Training included essential clinical and theoretical issues as well as clearly defined standard operation procedures, guidelines, and checklists to aid daily routine work and the management of challenging situations.

Mental health law in Finland.

A tradition of Romano-Germanic or civil law defines the legal system in Finland. Laws of relevance to psychiatry are the 1990 Mental Health Act and, insofar as it pertains to forensic psychiatry, the Criminal Law (1889) and the Law on State Mental Hospitals (1987, revised 1997). These are outlined in the present paper.

Neuronal collagen XVII is localized to lipofuscin granules.

We have earlier shown that collagen XVII is expressed by neurons in the human brain, although its exact intracellular location and function have remained unknown. In this study we have localized collagen XVII specifically to neuronal lipofuscin granules using electron microscopy in autopsy samples from the human brainstem. Our results show that collagen XVII expression is mainly confined to an ultrastructurally definable, specific type of lipofuscin granule. The function of neuronal collagen XVII remains unclear. However, as the functional significance of lipofuscin remains debated, the presence of collagen XVII in just some types of lipofuscin may be helpful in the process of exploring the variety of neuronal, age-related lipopigments, which are as yet defined operationally rather than functionally or structurally.

Expression of collagen XVII and ubiquitin-binding protein p62 in motor neuron disease.

Collagen involvement in motor neuron disease has been suggested by several earlier studies. Recently, we found collagen XVII to be expressed in locations in the human brain that include those damaged in motor neuron disease. In this study, we examined the extent of motor neuron disease-related changes in the brain of 9 subjects using ubiquitin-binding protein p62/sequestosome 1 (p62) immunohistochemistry. We then assessed whether or not the expression of collagen XVII was altered in relation to the p62 immunoreactive lesions. We found that neuronal collagen XVII expression in motor neuron disease remains similar to that seen in the normal human brain and thus a change in collagen XVII expression is not an immunohistochemically detectable feature of motor neuron disease. We also found that the regional distribution of p62 varied according to clinical presentation: p62 immunoreactive inclusions were found in the frontal cortex, hippocampus and cerebellum only in subjects with a history of psychiatric morbidity. Our study supports the re-definition of motor neuron disease as a multisystem disorder with a wide clinicopathological spectrum, and we advocate addressing psychiatric symptomology in future studies of motor neuron disease.