Clozapine and neutrophil response in patients of African descent: A six-month, multinational, prospective, open-label clinical trial.

INTRODUCTION: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific "ACKR1-null" ("Duffy null") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent. METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology. RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %). CONCLUSION: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.

Comparative Effects of Repetitive Odor Identification and Odor Memory Tasks on Olfactory Engagement in Older Populations - A Pilot fMRI Study.

OBJECTIVE: This study evaluated human Blood Oxygen Level-Dependent (BOLD) responses in primary and higher-order olfactory regions of older adults, using odor memory and odor identification tasks. The goal was to determine which olfactory and memory regions of interest are more strongly engaged in older populations comparing these two odor training tasks. METHODS: Twelve adults 55-75 years old (75% females) without intranasal or major neurological disorders performed repetitive odor memory and identification tasks using a 3-tesla magnetic resonance scanner. Odors were presented intermittently at 10-second bursts separated by 20-second intervals of odorless air. Paired t-tests were used to compare differences in the degree of activation between odor identification and odor memory tasks within individuals. An FDR cluster-level correction of p<0.05 was used for multiplicity of tests (with a cluster-defining threshold set at p<0.01 and 10 voxels). RESULTS: Odor identification compared to memory (ie, odor identification > odor memory) contrasts had several areas of significant activation, including many of the classical olfactory brain regions as well as the hippocampus. The opposite contrast (odor memory > odor identification) included the piriform cortex, though this was not significant. Both tasks equally activated the piriform cortex, and thus when the two tasks are compared to each other this area of activation appears to be either absent (OI > OM) or only weakly observed (OM > OI). CONCLUSION: These findings from a predominantly African American sample suggest that odor identification tasks may be more potent than memory tasks in targeted olfactory engagement in older populations. Furthermore, repetitive odor identification significantly engaged the hippocampus - a region relevant to Alzheimer's disease - more significantly than did the odor memory task. If validated in larger studies, this result could have important implications in the design of olfactory training paradigms.

Pandemia da COVID-19: repercussões no quotidiano da família de profissionais de saúde atuantes em unidades emergenciais / The COVID-19 pandemic: repercussions on the daily life of health professionals working in emergency units / Pandemia del COVID-19: repercusiones en el cotidiano familiar de profesionales sanitarios actuantes en unidades de urgencia

Objetivo: compreender as repercussões da pandemia da COVID-19 no quotidiano de familiares de profissionais de saúde atuantes em unidades de emergência. Métodos: estudo descritivo-exploratório de abordagem qualitativa, realizado com 18 familiares de profissionais de saúde atuantes em duas unidades de emergência localizadas no Sul do Brasil. Os dados foram coletados de setembro a novembro de 2020, mediante entrevistas telefônicas audiogravadas, posteriormente transcritas na íntegra. A análise foi realizada à luz da sociologia compreensiva. Resultados: as repercussões negativas da pandemia no quotidiano dos familiares foram marcadas pelo medo da atuação profissional na linha de frente e pela possibilidade de o familiar se contaminar, levando, por conseguinte, o vírus para os demais membros da família. Porém, paradoxalmente, houve repercussões positivas, como a união dos membros da família e maior aproximação da religiosidade/espiritualidade. Considerações finais e implicações para a prática: identifica-se como relevante o desenvolvimento de estratégias de comunicação para oferecer suporte emocional, promover encorajamento, reconhecimento das forças do sistema familiar e, se necessário, educação para que se diminuam as consequências negativas, como o estigma e as desavenças decorrentes dessa experiência

Objective: to understand the repercussions of the pandemic of COVID-19 in the daily lives of family members of health professionals working in emergency units. Methods: this is a qualitative descriptive-exploratory study conducted with 18 family members of health professionals working in two emergency units located in the South of Brazil. Data was collected from September to November 2020, through audio-recorded telephone interviews, later transcribed in full. The analysis was conducted in the light of the comprehensive sociology. Results: the negative repercussions of the pandemic in the daily life of family members were marked by the fear of professional performance in the front line and the possibility of the family member getting infected, thus taking the virus to the other members of the family. However, paradoxically, there were positive repercussions, such as the union of the family members and greater closeness to religiosity/spirituality. Final considerations and implications for the practice: the development of communication strategies to offer emotional support, promote encouragement, recognition of the family system's strengths and, if necessary, education to diminish the negative consequences, such as stigma and disagreements arising from this experience, is identified as relevant

Objetivo: comprender las repercusiones de la pandemia del COVID-19 en la vida cotidiana de los familiares de los profesionales sanitarios que laboran en las unidades de urgencia. Métodos: estudio descriptivo-exploratorio con abordaje cualitativo, realizado con 18 familiares de profesionales sanitarios que laboran en dos unidades de urgencias ubicadas en el sur de Brasil. Los datos fueron recolectados entre septiembre y noviembre de 2020, a partir de entrevistas telefónicas grabadas en audio, posteriormente transcritas íntegramente. El análisis se llevó a cabo a la luz de la sociología comprensiva. Resultados: las repercusiones negativas de la pandemia en la vida cotidiana de los familiares estuvieron marcadas por el miedo a la actividad profesional en primera línea y por la posibilidad de que el familiar se contagie, llevando el virus al resto de familiares. Sin embargo, paradójicamente, hubo repercusiones positivas, como la unión de los miembros de la familia y un acercamiento más próximo a la religiosidad / espiritualidad. Consideraciones finales e implicaciones para la práctica: se identifica como relevante el desarrollo de estrategias de comunicación para ofrecer apoyo emocional, promover el estímulo, el reconocimiento de las fortalezas del grupo familiar y, si es necesario, la educación para reducir las consecuencias negativas, como el estigma y los desacuerdos resultantes de esa experiencia

Efficient region-based test strategy uncovers genetic risk factors for functional outcome in bipolar disorder.

Genome-wide association studies of case-control status have advanced the understanding of the genetic basis of psychiatric disorders. Further progress may be gained by increasing sample size but also by new analysis strategies that advance the exploitation of existing data, especially for clinically important quantitative phenotypes. The functionally-informed efficient region-based test strategy (FIERS) introduced herein uses prior knowledge on biological function and dependence of genotypes within a powerful statistical framework with improved sensitivity and specificity for detecting consistent genetic effects across studies. As proof of concept, FIERS was used for the first genome-wide single nucleotide polymorphism (SNP)-based investigation on bipolar disorder (BD) that focuses on an important aspect of disease course, the functional outcome. FIERS identified a significantly associated locus on chromosome 15 (hg38: chr15:48965004 - 49464789 bp) with consistent effect strength between two independent studies (GAIN/TGen: European Americans, BOMA: Germans; n = 1592 BD patients in total). Protective and risk haplotypes were found on the most strongly associated SNPs. They contain a CTCF binding site (rs586758); CTCF sites are known to regulate sets of genes within a chromatin domain. The rs586758 - rs2086256 - rs1904317 haplotype is located in the promoter flanking region of the COPS2 gene, close to microRNA4716, and the EID1, SHC4, DTWD1 genes as plausible biological candidates. While implication with BD is novel, COPS2, EID1, and SHC4 are known to be relevant for neuronal differentiation and function and DTWD1 for psychopharmacological side effects. The test strategy FIERS that enabled this discovery is equally applicable for tag SNPs and sequence data.

Detecting significant genotype-phenotype association rules in bipolar disorder: market research meets complex genetics.

BACKGROUND: Disentangling the etiology of common, complex diseases is a major challenge in genetic research. For bipolar disorder (BD), several genome-wide association studies (GWAS) have been performed. Similar to other complex disorders, major breakthroughs in explaining the high heritability of BD through GWAS have remained elusive. To overcome this dilemma, genetic research into BD, has embraced a variety of strategies such as the formation of large consortia to increase sample size and sequencing approaches. Here we advocate a complementary approach making use of already existing GWAS data: a novel data mining procedure to identify yet undetected genotype-phenotype relationships. We adapted association rule mining, a data mining technique traditionally used in retail market research, to identify frequent and characteristic genotype patterns showing strong associations to phenotype clusters. We applied this strategy to three independent GWAS datasets from 2835 phenotypically characterized patients with BD. In a discovery step, 20,882 candidate association rules were extracted. RESULTS: Two of these rules-one associated with eating disorder and the other with anxiety-remained significant in an independent dataset after robust correction for multiple testing. Both showed considerable effect sizes (odds ratio ~ 3.4 and 3.0, respectively) and support previously reported molecular biological findings. CONCLUSION: Our approach detected novel specific genotype-phenotype relationships in BD that were missed by standard analyses like GWAS. While we developed and applied our method within the context of BD gene discovery, it may facilitate identifying highly specific genotype-phenotype relationships in subsets of genome-wide data sets of other complex phenotype with similar epidemiological properties and challenges to gene discovery efforts.

Illustrating and analyzing the processes of multi-institutional collaboration: Lessons learnt at Howard University Hospital.

Multi-institutional collaboration offers a promising approach to the dissemination of resources for capacity building and the improvement of the training of new investigators and residents, especially in areas of novel curricular content. Physicians should keep pace with the rapid growth of curricular content in an era of restricted resources. Such collaborations, in which educational entities work together and share resources and infrastructure, have been employed in health care to improve quality of care, capacity building, disparity reduction, and resident training. This paper examines a federally funded multi-institutional collaboration for the project STRIDE (Seek, Treat, Reach to Identify Pretrial Defendants Enhancement) between Yale University, George Mason University (GMU), and Howard University, a Historically Black University. The STRIDE study collaboration focused on mental health, opioid addiction, and infectious disease/HIV among Africans Americans involved in CJS (Criminal Justice System). We discuss some of the challenges and benefits of collaborative research projects conducted at Historically Black Colleges and University (HBCUs) and highlight the educational opportunities created by such collaborations for residents and other trainees, leading to the development of independent investigators through multi-institutional, structured collaborative research. We identify some unique challenges such as substance use, race, stigma, incarceration among participants, and the cultural and power difference between participating institutions, and thereby address these issues and how it impacted the course of the multi-institutional collaborative effort.

Overlapping Risky Decision-Making and Olfactory Processing Ability in HIV-Infected Individuals.

OBJECTIVE: Given neuroimaging evidences of overlap in the circuitries for decision-making and olfactory processing, we examined the hypothesis that impairment in psychophysical tasks of olfaction would independently predict poor performances on Iowa Gambling Task (IGT), a laboratory task that closely mimics real-life decision-making, in a US cohort of HIV-infected (HIV+) individuals. METHOD: IGT and psychophysical tasks of olfaction were administered to a Washington DC-based cohort of largely African American HIV+ subjects (N=100), and to a small number of demographically-matched non-HIV healthy controls (N=43) from a different study. Constructs of olfactory ability and decision-making were examined through confirmatory factor analysis (CFA). Structural equation models (SEMs) were used to evaluate the validity of the path relationship between these two constructs. RESULT: The 100 HIV+ participants (56% female; 96% African Americans; median age = 48 years) had median CD4 count of 576 cells/µl and median HIV RNA viral load <48 copies per milliliter. Majority of HIV+ participants performed randomly throughout the course of IGT tasks, and failed to demonstrate a learning curve. Confirmatory factor analysis provided support for a unidimensional factor underlying poor performances on IGT. Nomological validity for correlations between olfactory ability and IGT performance was confirmed through SEM. Finally, factor scores of olfactory ability and IGT performance strongly predicted 6 months history of drug use, while olfaction additionally predicted hallucinogen use. CONCLUSION: This study suggests that combination of simple, office-based tasks of olfaction and decision-making may identify those HIV+ individuals who are more prone to risky decision-making. This finding may have significant clinical, public health value if joint impairments in olfaction and IGT task correlates with more decreased activity in brain regions relevant to decision-making.

A Pilot Study of Reduced Olfactory Bulb Volume as a Marker of PTSD in Childhood Trauma-Exposed Adult HIV-Infected Patients.

Evidence suggests that olfactory bulb (OB), a key structure in odor processing, may also be involved in mechanisms of traumatic stress. In animals, chronic stress reduces OB plasticity, and olfactory bulbectomy results in stress-enhanced startle reflex and autonomic dysregulation. However, OB morphometry has not been adequately studied in the development of stress disorders following childhood trauma in humans. The researchers conducted a pilot study evaluating the relationships between OB volume, childhood trauma, and lifetime posttraumatic stress disorder (PTSD) in a sample of 16 HIV-positive individuals, 13 of whom were exposed to childhood trauma of 9 developed PTSD. Participants were recruited from a larger cohort of inner city-dwelling HIV-positive populations in Washington, DC. Mean OB volumes were significantly reduced when PTSD and non-PTSD groups were compared, p = .019, as well as when trauma-exposed PTSD-positive and trauma-exposed PTSD-negative groups were compared, p = .008. No significant difference was observed when trauma-exposed and nonexposed participants were compared. The association between PTSD and right OB volume remained strong p = 0.002 after adjusting for group differences in sex, age, depression, hippocampal volume, and total intracranial volume. Because this study is limited by small sample size, further elucidation of relationships between OB, trauma, and PTSD should be investigated in larger cross-sectional and prospective studies and in diverse cohorts.

Culturally Sensitive Approaches to Identification and Treatment of Depression among HIV Infected African American Adults: A Qualitative Study of Primary Care Providers' Perspectives.

BACKGROUND: Major depressive disorder (MDD) is highly prevalent among HIV-infected (HIV+) individuals, and is associated with non-adherence to antiretroviral therapy (ART), and accelerated disease progression. MDD is underdiagnosed and undertreated among low-income African Americans, who are disproportionately impacted by the HIV epidemic. To improve detection and treatment of depression among African Americans living with HIV/AIDS, it is important to understand culturally and contextually relevant aspects of MDD and attitudes about mental health treatment. METHODS: A focus group session was conducted with seven providers and staff at a primary care center that serves a largely African-American community heavily impacted by the HIV epidemic in Washington, DC. Data were analyzed using an inductive approach to distill prominent themes, perspectives, and experiences among participating providers. RESULTS: Five themes emerged to characterize the lived experiences of HIV+ African-American patients: (a) Changes in perceptions of HIV over time; (b) HIV is comorbid with mental illness, particularly depression and substance abuse; (c) Stigma is associated with both HIV and depression; (d) Existing mental health services vary and are insufficient and (e) Suggestions for optimal treatment for comorbid HIV and depression. LIMITATION: This study reflects the views of providers from one clinic in this community. CONCLUSION: Substantial economic disadvantage, pervasive childhood adversity, limited education and limited resources jointly put members of this community at risk for acquisition of HIV and for development of depression and addictions. These contextual factors provide an important reminder that any patient-level depression identification or intervention in this community will have to be mindful of such circumstances.

Inhibition of HIV-1 by curcumin A, a novel curcumin analog.

Despite the remarkable success of combination antiretroviral therapy at curtailing HIV progression, emergence of drug-resistant viruses, chronic low-grade inflammation, and adverse effects of combination antiretroviral therapy treatments, including metabolic disorders collectively present the impetus for development of newer and safer antiretroviral drugs. Curcumin, a phytochemical compound, was previously reported to have some in vitro anti-HIV and anti-inflammatory activities, but poor bioavailability has limited its clinical utility. To circumvent the bioavailability problem, we derivatized curcumin to sustain retro-aldol decomposition at physiological pH. The lead compound derived, curcumin A, showed increased stability, especially in murine serum where it was stable for up to 25 hours, as compared to curcumin that only had a half-life of 10 hours. Both curcumin and curcumin A showed similar inhibition of one round of HIV-1 infection in cultured lymphoblastoid (also called CEM) T cells (IC50=0.7 µM). But in primary peripheral blood mononuclear cells, curcumin A inhibited HIV-1 more potently (IC50=2 µM) compared to curcumin (IC50=12 µM). Analysis of specific steps of HIV-1 replication showed that curcumin A inhibited HIV-1 reverse transcription, but had no effect on HIV-1 long terminal repeat basal or Tat-induced transcription, or NF-κB-driven transcription at low concentrations that affected reverse transcription. Finally, we showed curcumin A induced expression of HO-1 and decreased cell cycle progression of T cells. Our findings thus indicate that altering the core structure of curcumin could yield more stable compounds with potent antiretroviral and anti-inflammatory activities.

Recovery in a family context: experiences of mothers with serious mental illnesses.

OBJECTIVE: Adults with mental illness are as likely as those without mental illness to be parents. Yet parenting and family life have received considerably less attention than employment, housing, and community integration in psychiatric rehabilitation and mental health services research. This ethnographic pilot study aimed to understand the lived experiences of urban low-income African American mothers diagnosed with serious mental illnesses. METHOD: Ethnographic observations and informal interviews were conducted over 12 months with three mothers diagnosed with serious mental illnesses and their children. Data were analyzed using a case study approach to distill prominent themes, perspectives, and experiences within and across participating families. RESULTS: Five themes emerged to characterize the lived experiences of African American mothers with serious mental illnesses: (a) mental illness and mental health services are not a prominent focus in everyday life; (b) families live in a context of ubiquitous violence, loss, and everyday stress; (c) family life is the main focus for mothers as they strive for a better life; (d) mothers have limited social support; and (e) religion is a source of meaning and a resource for the everyday work of recovery. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings from this exploratory pilot study suggest that rehabilitative efforts tailored for this population should not focus on, or reside in, professional mental health services. Meaningful rehabilitative strategies for families might include supported employment, social support, youth mentoring, faith-based supports, and community-based antiviolence efforts. Peer-based approaches may be a promising way to provide supports within this population.

Evidence for association of bipolar disorder to haplotypes in the 22q12.3 region near the genes stargazin, IFT27 and parvalbumin.

We have previously reported genome-wide significant linkage of bipolar disorder to a region on 22q12.3 near the marker D22S278. Towards identifying the susceptibility gene, we have conducted a fine-mapping association study of the region in two independent family samples, an independent case-control sample and a genome-wide association dataset. Two hundred SNPs were first examined in a 5 Mb region surrounding the D22S278 marker in a sample of 169 families and analyzed using PLINK. The peak of association was a haplotype near the genes stargazin (CACNG2), intraflagellar transport protein homolog 27 (IFT27) and parvalbumin (PVALB; P = 4.69 × 10(-4)). This peak overlapped a significant haplotype in a family based association study of a second independent sample of 294 families (P = 1.42 × 10(-5)). Analysis of the combined family sample yielded statistically significant evidence of association to a rare three SNP haplotype in the gene IFT27 (P = 8.89 × 10(-6)). Twelve SNPs comprising these haplotypes were genotyped in an independent sample of 574 bipolar I cases and 550 controls. Statistically significant association was found for a haplotype window that overlapped the region from the first two family samples (P = 3.43 × 10(-4)). However, analyses of the two family samples using the program LAMP, found no evidence for association in this region, but did yield significant evidence for association to a haplotype 3' of CACNG2 (P = 1.76 × 10(-6)). Furthermore, no evidence for association was found in a large genome-wide association dataset. The replication of association to overlapping haplotypes in three independent datasets suggests the presence of a bipolar disorder susceptibility gene in this region.

Genome-wide significant association between a 'negative mood delusions' dimension in bipolar disorder and genetic variation on chromosome 3q26.1.

Research suggests that clinical symptom dimensions may be more useful in delineating the genetics of bipolar disorder (BD) than standard diagnostic models. To date, no study has applied this concept to data from genome-wide association studies (GWAS). We performed a GWAS of factor dimensions in 927 clinically well-characterized BD patients of German ancestry. Rs9875793, which is located in an intergenic region of 3q26.1 and in the vicinity of the solute carrier family 2 (facilitated glucose transporter), member 2 gene (SLC2A2), was significantly associated with the factor analysis-derived dimension 'negative mood delusions' (n=927; P=4.65 × 10(-8), odds ratio (OR)=2.66). This dimension was comprised of the symptoms delusions of poverty, delusions of guilt and nihilistic delusions. In case-control analyses, significant association with the G allele of rs9875793 was only observed in the subgroup of BD patients who displayed symptoms of 'negative mood delusions' (allelic χ(2) model: P(G)=0.0001, OR=1.92; item present, n=89). Further support for the hypothesis that rs9875793 is associated with BD in patients displaying 'negative mood delusions' symptom, such as delusions of guilt, was obtained from an European American sample (GAIN/TGEN), which included 1247 BD patients and 1434 controls (P(EA)=0.028, OR=1.27).

Proteomic, genomic and translational approaches identify CRMP1 for a role in schizophrenia and its underlying traits.

Schizophrenia is a chronic illness of heterogenous biological origin. We hypothesized that, similar to chronic progressive brain conditions, persistent functional disturbances of neurons would result in disturbed proteostasis in the brains of schizophrenia patients, leading to increased abundance of specific misfolded, insoluble proteins. Identification of such proteins would facilitate the elucidation of molecular processes underlying these devastating conditions. We therefore generated antibodies against pooled insoluble proteome of post-mortem brains from schizophrenia patients in order to identify unique, disease-specific epitopes. We successfully identified such an epitope to be present on collapsin-response mediator protein 1 (CRMP1) in biochemically purified, insoluble brain fractions. A genetic association analysis for the CRMP1 gene in a large Finnish population cohort (n = 4651) corroborated the association of physical and social anhedonia with the CRMP1 locus in a DISC1 (Disrupted-in-schizophrenia 1)-dependent manner. Physical and social anhedonia are heritable traits, present as chronic, negative symptoms of schizophrenia and severe major depression, thus constituting serious vulnerability factors for mental disease. Strikingly, lymphoblastoid cell lines derived from schizophrenia patients mirrored aberrant CRMP1 immunoreactivity by showing an increase of CRMP1 expression, suggesting its potential role as a blood-based diagnostic marker. CRMP1 is a novel candidate protein for schizophrenia traits at the intersection of the reelin and DISC1 pathways that directly and functionally interacts with DISC1. We demonstrate the impact of an interdisciplinary approach where the identification of a disease-associated epitope in post-mortem brains, powered by a genetic association study, is rapidly translated into a potential blood-based diagnostic marker.

Capacity-building for African American mental health training and research: lessons from the Howard-Dartmouth Collaborative summer school.

BACKGROUND: Many psychiatric residents have traditionally received little-or-no training in cross cultural approaches to psychiatric training and research. METHOD: The Dartmouth-Howard Collaboration summer school training program had a 5-year grant to explore approaches to enhancing understanding of cultural factors in mental health treatment and research. RESULTS: Participants' questionnaire rating responses indicated that their experience in the Summer School program enhanced their understanding and experience in dealing with minority, largely African American patients and the diverse factors that affect their treatment. CONCLUSION: The Dartmouth-Howard Collaboration provides a model for a feasible training program that imparts knowledge regarding culture and mental health, and the conduct of mental health research, with particular attention to African American mental health. The program is unique in that it offers an intense, 1-week course delivered to several types of mental health professionals and trainees in research and practice.

"Right here is an oasis": how "recovery communities" contribute to recovery for people with serious mental illnesses.

OBJECTIVE: "Creating Communities" is a study that examines the influence of stable housing on recovery within intentional communities of people living with severe mental illnesses in Washington, DC. We label these configurations "recovery communities" (RCs). The authors aim to identify features of the contextual environment of RCs that contribute to recovery from the perspective of RC residents. METHOD: Focus groups were conducted with RC residents at 4-month intervals to inquire into day-to-day life in the communities. Focus group transcripts were reviewed and thematic analysis was conducted to identify prominent and emergent themes relating to the RC and recovery. RESULTS: Thematic analysis yielded three contextual domains through which study participants articulate the RC contributing to their recovery: (a) service environment, (b) physical environment, and (c) social environment. RCs are embedded in a complementary service system; the physical environment provides a refuge from homelessness, drug activity, and violence; and the social environment offers a place to "belong" amid peer-support for mental health and sobriety. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings suggest the need for recovery-oriented services to be holistic and prepared to address multiple, complex needs that include, but go beyond, clinical efforts to reduce psychiatric symptomatology, substance use, and the impact of trauma. People with serious mental illnesses living in RCs express the need for support that ranges from the very concrete to the less tangible, fundamental need for connection and belonging. As a rehabilitative strategy, RCs offer support for the mitigation of psychiatric challenges as well as a refuge from poverty and homelessness.

Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.

Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies.

Directiva sobre patentes del Instituto Nacional de Salud / Patent directive of the Instituto Nacional de Salud

la presente publicación describe los procedimientos para la protección de la titularidad y explotación de la propiedad intelectual, normados en todos los aspectos relacionados con los derechos derivados de propiedad intelectual que resulten de actividades desarrolladas por los investigadores o el personal administrativo bajo relación laboral con el Instituto Nacional de Salud(AU)

Directiva sobre patentes del Instituto Nacional de Salud / Patent directive of the Instituto Nacional de Salud

La publicación describe los procedimientos para la protección de la titularidad y explotación de la propiedad intelectual, normados en todos los aspectos relacionados con los derechos derivados de propiedad intelectual que resulten de actividades desarrolladas por los investigadores o el personal administrativo bajo relación laboral con el Instituto Nacional de Salud