Five-year follow-up of the iBerry Study: screening in early adolescence to identify those at risk of psychopathology in emerging adulthood.

The iBerry Study, a Dutch population-based high-risk cohort (n = 1022) examines the transition from subclinical symptoms to psychiatric disorders in adolescents. Here, we present the first follow-up measurement, approximately 3 years after baseline assessment and 5 years after the screening based on self-reported emotional and behavioral problems (SDQ-Y). We give an update on the data collection, details on the (non)response, and the results on psychopathology outcomes. The first follow-up (2019-2022) had a response rate of 79% (n = 807). Our results at baseline (mean age 15.0 years) have shown the effectiveness of using the SDQ-Y to select a cohort oversampled for the risk of psychopathology. At first follow-up (mean age 18.1 years), the previously administered SDQ-Y remains predictive for selecting adolescents at risk. At follow-up, 47% of the high-risk adolescents showed significant mental health problems based on self- and parent reports and 46% of the high-risk adolescents met the criteria for multiple DSM-5 diagnoses. Compared to low-risk adolescents, high-risk adolescents had a sevenfold higher odds of significant emotional and behavioral problems at follow-up. Comprehensive assessment on psychopathology, substance abuse, psychotic symptoms, suicidality, nonsuicidal self-injury, addiction to social media and/or video gaming, and delinquency, as well as social development, and the utilization of healthcare and social services were conducted. This wave, as well as the ones to follow, track these adolescents into their young adulthood to identify risk factors, elucidate causal mechanisms, and discern pathways leading to both common and severe mental disorders. Results from the iBerry Study will provide leads for preventive interventions.

Histological study on the influence of puberty suppression and hormonal treatment on developing germ cells in transgender women.

STUDY QUESTION: Can transgender women cryopreserve germ cells obtained from their orchiectomy specimen for fertility preservation, after having used puberty suppression and/or hormonal treatment? SUMMARY ANSWER: In the vast majority of transgender women, there were still immature germ cells present in the orchiectomy specimen, and in 4.7% of transgender women-who all initiated medical treatment in Tanner stage 4 or higher-mature spermatozoa were found, which would enable cryopreservation of spermatozoa or testicular tissue after having used puberty suppression and/or hormonal treatment. WHAT IS KNOWN ALREADY: Gender affirming treatment (i.e. puberty suppression, hormonal treatment, and subsequent orchiectomy) impairs reproductive function in transgender women. Although semen cryopreservation is generally offered during the transition process, this option is not feasible for all transgender women (e.g. due to incomplete spermatogenesis when initiating treatment in early puberty, in case of inability to masturbate, or when temporary cessation of hormonal treatment is too disruptive). Harvesting mature spermatozoa, or testicular tissue harboring immature germ cells, from orchiectomy specimens obtained during genital gender-affirming surgery (gGAS) might give this group a chance of having biological children later in life. Previous studies on spermatogenesis in orchiectomy specimens showed conflicting results, ranging from complete absence of germ cells to full spermatogenesis, and did not involve transgender women who initiated medical treatment in early- or late puberty. STUDY DESIGN, SIZE, DURATION: Histological and immunohistochemical analyses were performed on orchiectomy specimens from 214 transgender women who underwent gGAS between 2006 and 2018. Six subgroups were identified, depending on pubertal stage at initiation of medical treatment (Tanner stage 2-3, Tanner stage 4-5, adult), and whether hormonal treatment was continued or temporarily stopped prior to gGAS in each of these groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: All transgender women used a combination of estrogens and testosterone suppressing therapy. Orchiectomy specimen sections were stained with Mayer's hematoxylin and eosin and histologically analyzed to assess the Johnsen score and the ratio of most advanced germ cell types in at least 50 seminiferous tubular cross-sections. Subsequently, immunohistochemistry was used to validate these findings using spermatogonia, spermatocytes or spermatids markers (MAGE-A3/A4, γH2AX, Acrosin, respectively). Possibilities for fertility preservation were defined as: preservation of spermatozoa, preservation of spermatogonial stem cells or no possibilities (in case no germ cells were found). Outcomes were compared between subgroups and logistic regression analyses were used to assess the association between the duration of hormonal treatment and the possibilities for fertility preservation. MAIN RESULTS AND THE ROLE OF CHANCE: Mature spermatozoa were encountered in 4.7% of orchiectomy specimens, all from transgender women who had initiated medical treatment in Tanner stage 4 or higher. In 88.3% of the study sample orchiectomy specimens only contained immature germ cells (round spermatids, spermatocytes or spermatogonia, as most advanced germ cell type). In 7.0%, a complete absence of germ cells was observed, all these samples were from transgender women who had initiated medical treatment in adulthood. Cessation of hormonal treatment prior to gGAS did not affect the presence of germ cells or their maturation stage, nor was there an effect of the duration of hormonal treatment prior to gGAS. LIMITATIONS, REASONS FOR CAUTION: Since data on serum hormone levels on the day of gGAS were not available, we were unable to verify if the transgender women who were asked to temporarily stop hormonal treatment 4 weeks prior to surgery actually did so, and if people with full spermatogenesis were compliant to treatment. WIDER IMPLICATIONS OF THE FINDINGS: There may still be options for fertility preservation in orchiectomy specimens obtained during gGAS since a small percentage of transgender women had full spermatogenesis, which could enable cryopreservation of mature spermatozoa via a testicular sperm extraction procedure. Furthermore, the vast majority still had immature germ cells, which could enable cryopreservation of testicular tissue harboring spermatogonial stem cells. If maturation techniques like in vitro spermatogenesis become available in the future, harvesting germ cells from orchiectomy specimens might be a promising option for those who are otherwise unable to have biological children. STUDY FUNDING/COMPETING INTEREST: None. TRIAL REGISTRATION NUMBER: N/A.

[Differences in the prevalence of acute involuntary admissions between Apeldoorn, Rotterdam and Amsterdam]. / Prevalentie van acute onvrijwillige opnames in Apeldoorn, Rotterdam en Amsterdam.

BACKGROUND: There are regional differences in the Netherlands in the numbers of emergency compulsory admissions (Inbewaringstelling: IBS). We looked at three 24/7 facilities to investigate the relationships between patient and consultation characteristics on the one hand, and numbers of emergency compulsory admissions on the other, against the background of the level of urbanisation. METHOD: We compared emergency consultations in 18-64 year olds in Apeldoorn, Amsterdam and Rotterdam between 2012 and 2016 in terms of socio-demographic, procedural and clinical characteristics, and in terms of outcome. We used the Severity of Psychiatric Illness Scale (SPI) to determine disorder severity. RESULTS: Apeldoorn had as many consultations per 100,000 inhabitants as the highly urbanised city of Rotterdam. GPs there referred 68% of patients, compared with 25% in Amsterdam and 50% in Rotterdam. In Apeldoorn, 17% of the patients were psychotic, compared with 35% in the other regions. In addition, 66% of the patients there had a low SPI score, compared with 40% in the large cities. Amsterdam and Rotterdam had 3.5 times higher risk of emergency compulsory admissions as Apeldoorn. After adjustment for socio-demographic, procedural and clinical characteristics, this difference with Apeldoorn was 1.5 for Amsterdam and 2.6 for Rotterdam. SPI score and psychotic disorder were found to be the most important predictors of IBS admission. CONCLUSION: Differences in consultation numbers, referral patterns and the location of consultations indicate that there are regional differences in the position of the 24/7 facility in the mental health care system. The numbers of emergency compulsory emissions were related in part to the level of urbanisation and the associated epidemiological differences but probably also to differences in the position of the crisis facility in the mental health care system. Differences in admission numbers were primarily linked to differences in diagnostic characteristics and disorder severity and, to a lesser extent, to referral patterns and socio-demographic characteristics. However, these variables did not explain all the observed inter-regional differences.

[Assertive Treatment as a regular function within mental health]. / Van bemoeizorg naar assertieve behandeling als regulier aanbod vanuit de ggz.

BACKGROUND: The setting for providing assertive treatment (AT) has changed during the last 30 years in The Netherlands from assertive community treatment (ACT) and flexible assertive community treatment (FACT) to municipalities. The provision of AT varies between municipalities. AIM: Describing the concept of AT, the nature and size of the target group, and the reasons why people with severe mental illness (SMI) do not seek treatment and the place of AT in mental health care. METHOD: We used literature en available quantitative data. RESULTS: AT regularly provided by mental health care is required in patients with SMI and social problems who do not seek treatment. When mental health care and social care collaborate on the level of the patient, treatment and handling of social problems can strengthen each other. This collaboration prevents discontinuity of care and breaking a trusting relationship because patients do not need to be transferred from social service to mental health care or vice versa. AT is on the continuum of voluntarily to compulsory care.AT provided by mental health care (usually provided by FACT-teams) is indicated for SMI patients with social problems and who do not seek treatment. The size of the target group is around 5000 - 20.000 patients in The Netherlands. Reasons not to seek help for people with SMI include within person factor, mental health related factors, or factors related to the interaction of SMI patients and mental health. We advocate for AT to become a regular part of mental health care, and for mental health care and social domain professionals to collaborate on case level. Acting this way, mental health treatment and addressing social problems can reinforce each other and discontinuity of care and breaking a trusting relationship can be prevented. AT is on the continuum of voluntary to involuntary treatment. That is why we suggest AT to be a better term than assertive outreach. CONCLUSION: It is a given fact that not all patients with SMI and social problems seek treatment. By making AT a regular part of mental health services, we prevent discontinuity of care and we fill the gap between voluntarily and compulsory care.

[High and intensive care as a next step in the reduction of coercion]. / High en intensive care als een volgende stap in dwangreductie.

BACKGROUND: The high and intensive care (HIC) model provides a framework for acute admission wards and is being implemented since 2013 by all mental healthcare institutions in the Netherlands. AIM: To investigate how the HIC model has been implemented between 2014 and 2018 and how the implementation of the HIC model is associated to coercive measures. METHOD: Between 2014 and 2018, 79 audits were organized in two phases within 25 institutions to measure the degree of implementation of HIC using a model fidelity scale, the HIC monitor. HIC monitor scores were compared to data on coercion to determine the relationship between implementation of the HIC model and coercive measures. RESULTS: Scores on the HIC monitor increased over time, especially in terms of vision, hospitality and facilities. However, a third of wards scored lower on the HIC monitor in the second audit compared to the first audit. Institutions that score higher use less seclusion and use less forced medication. CONCLUSION: Progress in the implementation of the HIC model is visible and institutions that are further in the implementation of the HIC model apply less coercion. Securing implementation proves difficult. Attention should be paid to the national staff shortage and systematic evaluation of coercion.

Cardio-metabolic risk factors among young infertile women: a systematic review and meta-analysis.

BACKGROUND: There is currently no concise systematic review or meta-analysis addressing cardio-metabolic risk factors in women experiencing infertility. OBJECTIVES: To determine whether infertile women have higher levels of cardiovascular risk factors compared with fertile women. SEARCH STRATEGY: We performed a systematic literature search using PubMed, Embase and CINAHL, Scopus and additional manual and bibliographic searches for relevant articles (end search date 6 November 2019). SELECTION CRITERIA: We selected studies that compared cardio-metabolic risk factors in fertile and infertile women of reproductive age. DATA COLLECTION AND ANALYSIS: At least two authors independently screened potentially eligible studies. MAIN RESULTS: There was an increased presence of several cardio-metabolic risk factors in infertile women compared with fertile women. Infertile women had statistically significant higher body mass index (BMI), increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) compared with fertile women. Fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and mean arterial pressure were not found to be different between fertile and infertile women. A subgroup analysis revealed that TC, fasting glucose and fasting insulin were increased, and high-density lipoprotein was decreased only in women with polycystic ovarian syndrome compared with fertile women, whereas BMI, TG and LDL-C were statistically significantly increased in women with any indication of infertility compared with fertile women. CONCLUSIONS: Infertile women have a higher level of cardio-metabolic risk factors compared with fertile women. This finding has clinical implications for infertile women in general, and those attempting to conceive through medically assisted reproduction. TWEETABLE ABSTRACT: Infertile women appear to have a higher level of cardio-metabolic risk factors compared with fertile women.

Does high and intensive care reduce coercion? Association of HIC model fidelity to seclusion use in the Netherlands.

BACKGROUND: A new inpatient care model has been developed in the Netherlands: High and Intensive Care (HIC). The purpose of HIC is to improve quality of inpatient mental healthcare and to reduce coercion. METHODS: In 2014, audits were held at 32 closed acute admission wards for adult patients throughout the Netherlands. The audits were done by trained auditors, who were professionals of the participating institutes, using the HIC monitor, a model fidelity scale to assess implementation of the HIC model. The HIC model fidelity scale (67 items) encompasses 11 domains including for example team structure, team processes, diagnostics and treatment, and building environment. Data on seclusion and forced medication was collected using the Argus rating scale. The association between HIC monitor scores and the use of seclusion and forced medication was analyzed, corrected for patient characteristics. RESULTS: Results showed that wards having a relatively high HIC monitor total score, indicating a high level of implementation of the model as compared to wards scoring lower on the monitor, had lower seclusion hours per admission hours (2.58 versus 4.20) and less forced medication events per admission days (0.0162 versus 0.0207). The HIC model fidelity scores explained 27% of the variance in seclusion rates (p < 0.001). Adding patient characteristics to HIC items in the regression model showed an increase of the explained variance to 40%. CONCLUSIONS: This study showed that higher HIC model fidelity was associated with less seclusion and less forced medication at acute closed psychiatric wards in the Netherlands.

Compulsory treatment in patients' homes in the Netherlands: what do mental health professionals think of this?

BACKGROUND: Compulsory treatment in patients' homes (CTH) will be introduced in the new Dutch mental health legislation. The aim of this study is to identify the opinions of mental health workers in the Netherlands on compulsory community treatment (CCT), and particularly on compulsory treatment in the patients' home. METHODS: This is a mixed methods study, comprising a semi-structured interview and a survey. Forty mental health workers took part in the semi-structured interview about CCT and 20 of them, working in outpatient services, also completed a questionnaire about CTH. Descriptive analyses were performed of indicated (dis) advantages and problems of CCT and of mean scores on the CTH questionnaire. RESULTS: Overall, the mental health workers seemed to have positive opinions on CCT. With respect to CTH, all mean scores were in the middle of the range, possibly indicating that clinicians were uncertain regarding safety issues and potential practical problems accompanying the use of CTH. CONCLUSIONS: The majority of the participating mental health workers in this study had a positive attitude towards CCT, but they seemed relative uncertain about potential possibilities and problems of working with CTH.

[Regional differences in compulsory treatment in mental health care in the Netherlands during 2013-2017]. / Gedwongen opnames en ambulante dwang in de ggz: onderzoek naar regionale verschillen tussen arrondissementen, leeftijdsgroepen en unieke personen, 2013-2017.

BACKGROUND: Compulsory treatment in mental health care has continuously increased for years. Registration of court ordered compulsory psychiatric care is based upon counts of legal authorisations. These counts do not refer to number of individual persons involved.
AIM: To report the number age-specific prevalence of coercion in psychiatric care, number of persons involved, age distribution and regional differences.
METHOD: Analysis of the number of requests for compulsory care and population size according to the age groups for the years 2013-2017. We used direct age standardisation at the level of jurisdiction regions.
RESULTS: The annual number of unique persons for whom compulsory care was requested was 28% less than the number of requested court orders. The annual increase in compulsory care was 3%. Per specific treatment order the increase during 2013-2017 was 12% for emergency compulsory admissions, 8% for hospital admissions, 10% for extended hospital admissions and 43% for community treatment order.
CONCLUSION: The number of persons for whom compulsory mental care is requested increased on average by 3% each year. Greatest increase was observed for age groups 25-44 years and 80 years and older. After age-standardisation substantial differences remain between jurisdiction regions.

[Mental health in Eastern Lille: a future of network-psychiatry?] / De ggz in Oost-Lille: inspiratie voor de praktijk van netwerkzorg in de ggz.

BACKGROUND: For some time now, East Lille has been working with a relatively modern mental health care system that remarkably resembles Dutch health care with the same values and norms that we want to implement in the Netherlands as well.
AIM: Gaining inspiration to further investigate regional cooperation and 'network care' in Dutch psychiatry.
METHOD: A delegation from the board of f-act-Netherlands and ccaf paid a working visit to Lille.
RESULTS: The basis of the East Lille working method is a charter of shared values developed with all parties, clients, relatives, employees and external professionals, which is signed by every professional. In case of doubt, a change of context or the introduction of new working methods, these values are used first. CONCLUSIONS High quality mental health care develops in dialogue, in which working methods, service delivery models and interventions are linked to each other by means of network care. Through reflection, moral deliberation and appreciative auditing, care is progressively improved. These procedures guarantee a modern process of quality improvement.

[Flexible assertive community treatment (FACT) as part of a community (health) network]. / FACT als onderdeel van wijkgerichte zorg in het (zorg)netwerk.

BACKGROUND: Community-based care for people with severe mental illness increasingly requires far-reaching cooperation between different domains. This cooperation must always be unique and local, and at the same time provide an answer to generic and nationally set goals.
AIM: Offering new insights on collaboration within and between domains.
METHOD: Reflection on developments in the social domain and specialist mental healthcare using relevant literature and recent (inter)national experiences.
RESULTS: It seems possible to provide better integral care by allowing FACT-teams to network together with Social Support partners (e.g. by sharing financial and/or human resources). In this process, networks of care for people with serious mental illness (SMI), develop over various phases and realize new partnerships. The model fidelity scale for FACT-teams was adjusted to facilitate that process. CONCLUSIONS The new FACT model fidelity scale is ready to allow FACT-teams to explore flexible local solutions for partnerships to realize the much-needed multi-domain integrated community care for people with SMI.

Clinical effects and treatment outcomes of long-term compulsory in-patient treatment of treatment-resistant patients with severe mental illness and substance-use disorder.

BACKGROUND: The treatment of homeless dual-diagnosis patients (i.e., those with severe mental illness and substance-use disorder) is difficult and often fails. For patients in the Netherlands who had not responded to earlier voluntary and compulsory treatment, a new treatment facility - Sustainable Residence (SuRe) - was developed to offer long-term compulsory in-patient treatment. AIM OF THE STUDY: To study patterns of changes in clinical and functional outcomes during treatment at SuRe and how these relate to eventual treatment outcome. METHODS: On the basis of the intensity of care needed after four years, three groups of patients were distinguished (total n = 165): those discharged to a less restrictive and less supportive setting (n = 70, 42%), those still hospitalized at SuRe at the end of the four-year study period (n = 69, 42%) and those referred to a more appropriate setting (n = 26, 16%). Random coefficient analysis was used to examine differences between groups regarding changes in clinical and functional outcomes during treatment. During treatment, outcomes were monitored using Routine Outcome Assessment. RESULTS: All three groups made small but significant improvements on global psychosocial functioning, distress and therapeutic alliance (effect sizes (ES) 0.11 to 0.16 per year). Patients who were discharged to a less restrictive setting showed small to moderate improvement in risk to self and others, psychiatric symptoms, and skills for daily living (ES 0.19-0.33 per year and 0.42-0.73 for their mean 2.2-year treatment period). Patients remaining at SuRe showed a small increase in risk to self (ES 0.20 per year; 0.80 for their treatment period of four years or more). Oppositional behaviour was consistently greater in referred patients than in the other groups (ES 0.74-0.75). CONCLUSION: Long-term compulsory treatment appeared to have helped improve clinical and functional outcomes in a substantial proportion (42%) of previously severely dysfunctional, treatment-resistant dual-diagnosis patients, who could then be discharged to a less restrictive and less supportive environment. However, risk-to-self increased in a similar proportion. A smaller number of patients (16%) showed marked oppositional behaviour and needed a higher level of care and protection in another facility.

High and Intensive Care in Psychiatry: Validating the HIC Monitor as a Tool for Assessing the Quality of Psychiatric Intensive Care Units.

This study aims to validate the HIC monitor as a model-fidelity scale to the High and Intensive Care (HIC) model, a recently developed model for acute psychiatric wards. To assess the psychometric properties of the HIC monitor, 37 audits were held on closed inpatient wards at 20 psychiatric hospitals in the Netherlands. Interrater reliability, construct validity and content validity were examined. Our results suggest that the HIC monitor has good psychometric properties. It can be used as a tool for assessing the implementation of the HIC model on acute psychiatric wards in the Netherlands, and for quality assessment and improvement.

[Modifications in therapy for patients with severe mental illness and intellectual disability: a qualitative study]. / Aanpassingen in behandeling van patiënten met ernstige psychiatrische aandoeningen en een lichte verstande-lijke beperking; een kwalitatief onderzoek.

BACKGROUND: In ambulant psychiatric care, intellectual disability (id) is often not recognised. Therefore, a Screener for Intelligence and Learning disabilities (scil) was recently introduced to assist recognition. However, because, current therapy is not adjusted for id-related problems, its effectiveness remains unknown.
AIM: To gain insight into adequate adaptation of interventions by professionals for patients with severe mental illness (smi) and id, to improve the quality of care without the need to develop a completely new program of therapy.
METHOD: A qualitative design (n=15) including 8 interviews and one focus group, among psychiatric practitioners and id experts.
RESULTS: Five main themes were identified to adjust therapy: treatment, communication, inclusion of the network, estimation of support needs and self-management. CONCLUSIONS To align therapy with the requirements of patients with smi and id, a patient-oriented approach to care is necessary. Simple but effective modifications, summarised in a toolkit, appear to contribute to this. To offer appropriate care to patients with smi and id, attention is needed for both a support-oriented and a recovery-oriented approach.

[Efficacy of integrated dual disorder treatment for dual disorder patients: a systematic literature review]. / Geïntegreerd behandelen van patiënten met dubbele diagnose met integrated dual diagnosis treatment (IDDT): systematische literatuurstudie.

BACKGROUND: Dual diagnosis (substance use disorder combined with a comorbid mental illness) is a common problem. One of the methods to treat this is integrated dual diagnosis treatment (IDDT). IDDT consists of the simultaneous, integrated application of different treatment components. Their efficacy, however, has only been studied separately. As a result, the effectiveness of the IDDT program as a whole remains unclear. AIM: To evaluate the scientific evidence relevant to the effectiveness of IDDT in dual diagnosis patients. METHOD: A systematic literature review using MEDLINE, Embase and PsycINFO (Prisma guideline). RESULTS: Six studies were found: a randomised controlled study (RCT), two non-randomised controlled studies, and three uncontrolled pre-post studies . There was a notably large diversity in outcome measures. The results differed significantly, including some studies concluding a significant (additional) effect, while others concluded that there was no indication of a significant effect of IDDT. CONCLUSION: In clinical practice, IDDT is recommended and chosen frequently as the treatment for patients with dual diagnosis. However, it is remarkable how limited and unthorough the research is pertaining to the effects of the full IDDT program on dual diagnosis.

[Model fidelity of flexible assertive community treatment (F-ACT) teams: five years of audit results]. / Modelgetrouwheid van flexible assertive community treatment(F-ACT)-teams: resultaten van vijf jaar auditeren.

BACKGROUND: The Flexible act (f-act) has been introduced in the Netherlands since 2004, alongside the Assertive Community Treatment (act) model. An estimate of 400 (f-)act teams concurrently provide care to approximately 70.000 people with serious mental illness. The ccaf has been assessing the model fidelity of act and f-act teams since 2009 to promote the quality and transparency of healthcare for clients with serious mental illness. OBJECTIVE To describe the state of implementation of f-act and associated trends in the Netherlands.
METHOD: Analysis of the ccaf database, which holds the data of audits conducted between 2009 and 2014.
RESULTS: The audits conducted by ccaf between 2009 and 2014 indicated an adequate implementation of f-act. The team foundations were well organized, featuring a multidisciplinary team structure, management of medication, practical support and investment in healthcare continuity, including during an admission. However, the results regarding participation and recovery were unsatisfactory. Furthermore, the results depicted a decline in the scores concerning a number of areas, including outreach and support of participation and recovery. CONCLUSIONS Although the data indicates an on average satisfactory implementation of f-act in the Netherlands, there are signs that the implementation of f-act is under pressure with relatively fewer home visits, a rising caseload and a reduced investment in recovery and participation. The findings are in accordance with the signs and arguments to adjust the emphasis on reducing hospital admissions, prioritizing the consolidation of outpatient care instead.

Meta-analysis of genome-wide association studies of anxiety disorders.

Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.

[Mental health as a front-line service for bewildered persons]. / Expertise van de ggz in de frontlinie bij de zorg voor personen met verward gedrag ofwel met acute (zorg)nood.

BACKGROUND: 'Bewildered persons' have often been in the news over the last few years. There has been much discussion about the meaning of the term 'bewildered persons', the number of people involved, the way the problem should be tackled and the role of the mental health services.
AIM: To look critically at the term 'bewildered persons' and to discuss the suspected increase in numbers and the role of mental health services.
METHOD: Review and discussion of the relevant literature relating to 'bewildered persons' which has been published in the last 25 years.
RESULTS: The term 'bewildered persons' is a general label given by the Dutch police to several groups of people. Suicide rates are rising and more and more people are being compulsorily admitted to psychiatric clinics and hospitals. These factors indicate that increasing numbers of people may now be a danger to themselves and to their fellow-citizens. It is not clear whether the increase in numbers is real or simply reflects the extra attention given by the police. These people may in fact be a new group consisting of persons already known to the mental health services. A national team that aims to improve the care of 'bewildered persons' has made several recommendations to stop the increase: prevention and better cooperation between municipalities and mental health facilities. In our view the mental health services should operate at the front-line of the public mental health service, providing low-threshold diagnostics, assertive outreach and treatment for patients who have mental disorders but are unwilling to accept care or treatment. Such a service requires adequate finance, good cooperative agreements and removal of the bureaucratic and financial barriers that prevent patients from seeking care.
CONCLUSION: 'Bewildered persons' is an umbrella term used to denote people who urgently require care and are a public nuisance and who display disturbing behavior. 'Bewildered persons', who now form a part of the group of people targeted by the public health services, have been around for a long time but have been referred to by different names. They require the structured assistance of integrated care, access to social and medical services and timely diagnosis and treatment. People who have somehow slipped through the net of care facilities should not be left to fend for themselves.

[Intensive home treatment: a first observational evaluation]. / Intensive home treatment: een eerste observationele evaluatie.

BACKGROUND: Yulius intensive home treatment (iht) offers six weeks of home-care to psychiatric patients in crisis who would normally be hospitalised.
AIM: To study patient characteristics and the content and outcomes of iht.
METHOD: We followed the handling of 75 consecutive applications for iht. Details were recorded before and after admission to the treatment.
RESULTS: Fifteen patients were referred in order to shorten the period of hospitalisation, and 60 were referred in order to prevent hospitalisation; 59 of the 75 persons admitted for the treatment received iht, and 41 patients finished the six-week module and provided follow-up data. Psychiatric symptoms improved significantly, suicidality was reduced, the caregiver's burden became much lighter and the evaluation by both patient and caregiver was very positive. iht was sufficient to prevent the need for hospitalisation of 75% of the patients referred for reduced hospitalisation, and it was also adequate to prevent the hospitalisation of more than 91% of patients referred for that particular purpose.
CONCLUSION: iht is highly appreciated and is possibly a good alternative to hospitalisation. However, in the future there will have to be randomised, controlled research in order to determine the effectiveness of iht compared to hospitalisation.

[Working methods of ambulatory psychiatric emergency services in the Netherlands]. / Werkwijze van ambulante psychiatrische crisisdiensten in Nederland.

BACKGROUND: No recent information is available concerning the working methods of the ambulatory psychiatric emergency services in The Netherlands.
AIM: To obtain insight into the working methods of the ambulatory psychiatric emergency services.
METHOD: We performed a descriptive research.
RESULTS: Twenty of the 28 ambulatory psychiatric emergency services participated in our study (more than 71 %). The study revealed that some of the ambulatory psychiatric emergency services used differing procedures. However, all the services had a common target: they dealt with young people, adults and the elderly. In half of the organisations it was the community mental health nurse who initially went alone to visit a prospective patient. There are large differences in the number of face-to-face contacts made by emergency services and in the type of medication provided before the patient was taken by ambulance to a psychiatric hospital.
CONCLUSION: In our study we describe the working methods used by several of the ambulatory psychiatric emergency services in the Netherlands. However, our investigation produced only limited information because participating institutions were often unable to provide the information we requested and/or they did not record the methods they had used. More attention needs to be given to the best way of dealing with patients who already have an official 'emergency card'; in addition, more information is required about whether the medication used by the emergency services influenced the subsequent course of the treatment that a patient received. In view of the current situation certain important features of the emergency services such as the quality of care they provided remains underexposed.