Cell-Type Specific Transcriptomic Profiling to Dissect Mechanisms of Differential Dendritogenesis

The establishment, maintenance and modulation of cell-type specific neural architectures are critically important to the formation of functional neural networks. At the neuroanatomical level, differential patterns of dendritic arborization directly impact neural function and connectivity, however the molecular mechanisms underlying the specification of distinct dendrite morphologies remain incompletely understood. To address this question, we analyzed global gene expression from purified populations of wild-type class I and class IV Drosophila melanogaster dendritic arborization (da) sensory neurons compared to wild-type whole larval RNA using oligo DNA microarray expression profiling. Herein we present detailed experimental methods and bioinformatic anal- yses to correspond with our data reported in the Gene Expression Omnibus under accession number GSE46154. We further provide R code to facilitate data accession, perform quality controls, and conduct bioinformatic analyses relevant to this dataset. Our cell-type specific gene expression datasets provide a valuable resource for guiding further investigations designed to explore the molecular mechanisms underlying differential patterns of neuronal patterning

Pathways to mental health services for young people: a systematic review

Purpose: While early access to appropriate care can minimise the sequelae of mental illnesses, little is known about how youths come to access mental healthcare. We therefore conducted a systematic review to synthesise literature on the pathways to care of youths across a range of mental health problems. Methods: Studies were identified through searches of electronic databases (MEDLINE, PsycINFO, Embase, HealthSTAR and CINAHL), supplemented by backward and forward mapping and hand searching. We included studies on the pathways to mental healthcare of individuals aged 11–30 years. Two reviewers independently screened articles and extracted data. Results: Forty-five studies from 26 countries met eligibility criteria. The majority of these studies were from settings that offered services for the early stages of psychosis, and others included inpatient and outpatient settings targeting wide-ranging mental health problems. Generally, youths’ pathways to mental healthcare were complex, involved diverse contacts, and, sometimes, undue treatment delays. Across contexts, family/carers, general practitioners and emergency rooms featured prominently in care pathways. There was little standardization in the measurement of pathways. Conclusions: Except in psychosis, youths’ pathways to mental healthcare remain understudied. Pathways to care research may need to be reconceptualised to account for the often transient and overlapping nature of youth mental health presentations, and the possibility that what constitutes optimal care may vary. Despite these complexities, additional research, using standardized methodology, can yield a greater understanding of the help-seeking behaviours of youths and those acting on their behalf; service responses to help-seeking; and the determinants of pathways. This understanding is critical to inform ongoing initatives to transform youth mental healthcare

Our roles are not at ease: The work of engaging a youth advisory council in a mental health services delivery organization

Objectives: There is growing policy impetus for including youth voices in health services research and health system reform. This article examines the perspectives of professionals in a mental healthcare organization charged with engaging young people as advisors in service transformation. Methods: An institutional ethnography of a youth mental health services organization in Ontario, Canada, was conducted. Fieldwork consisted of twelve months of observation of meetings, interviews with youth advisors and adult service providers, with subsequent text analysis of engagement training and policy materials. The present article reports data from six adult professionals and related field observations. Results: Service providers’ efforts to engage youth were observed in three areas: a) supporting youth\u27s development as advisors, b) retaining and deepening youth participation while waiting for organizational change and c) embedding relationships between youth and adults at various levels within the system of care. This work denotes existing tensions between the values and ideals of youth engagement and the everyday demands of services delivery. Conclusion: In this setting, a fundamental dimension of this work consisted of negotiating tensions between the policy enthusiasm for engagement and its realization in a health services context. In describing these contextual challenges, we outline implications for consideration by other youth mental health services. Engagement efforts that are authentic and sustained require resources and flexibility, and leadership commitment to instil service users’ perspectives throughout multiple levels within the organization

“Youth as accessories”:Stakeholder Perspectives on Youth Participation in Mental Health Policymaking [Part II]

PURPOSE: To elicit stakeholder perspectives on the findings from our scoping review on youth participation in mental health policymaking, we conducted a global consultation with young people and adults directly involved in mental health policymaking. METHOD: Forty-four stakeholders from 16 countries, including 15 young people, 9 policymakers and 20 facilitators of youth participation, took part in individual interviews and/or focus groups. They were asked about how the review findings contrasted with their own experiences in mental health policymaking. The transcribed data were thematically analyzed. RESULTS: All participants viewed lived experience as valuable in identifying policy gaps. Youth pointed out that children and youth with disabilities, diverse sexual orientations, and/or gender identities were often excluded, and spoke about feelings of being an “accessory”, illustrating a lack of power-sharing in a tokenized policymaking process. Adult participants’ accounts highlighted the challenges inherent in policymaking such as the need for political knowledge and institutional time constraints. A range of cultural, socio-economic, and political barriers to youth participation, that were often context-specific, were identified. CONCLUSIONS: The diverse perspectives of stakeholders extended the review results. Based on our findings, we recommend that adults and institutions: (1) recognize lived experience as expertise in shaping mental health policies; (2) include diverse groups; (3) reduce tokenistic relationships through the creation of safer spaces, adult feedback, co-production, and social accountability; and (4) adopt an intersectional approach to address cultural, socio-economic, and political barriers to participation. Methodologically, our work demonstrates why stakeholder consultations are an essential component of scoping reviews

Pathways to care in first-episode psychosis in low-resource settings: Implications for policy and practice.

Developing countries such as India face a major mental health care gap. Delayed or inadequate care can have a profound impact on treatment outcomes. We compared pathways to care in first episode psychosis (FEP) between North and South India to inform solutions to bridge the treatment gap. Cross-sectional observation study of 'untreated' FEP patients (n = 177) visiting a psychiatry department in two sites in India (AIIMS, New Delhi and SCARF, Chennai). We compared duration of untreated psychosis (DUP), first service encounters, illness attributions and socio-demographic factors between patients from North and South India. Correlates of DUP were explored using logistic regression analysis (DUP ≥ 6 months) and generalised linear models (DUP in weeks). Patients in North India had experienced longer DUP than patients in South India (β = 17.68, p < 0.05). The most common first encounter in North India was with a faith healer (45.7%), however, this contact was not significantly associated with longer DUP. Visiting a faith healer was the second most common first contact in South India (23.6%) and was significantly associated with longer DUP (Odds Ratio: 6.84; 95% Confidence Interval: 1.77, 26.49). Being in paid employment was significantly associated with shorter DUP across both sites. Implementing early intervention strategies in a diverse country like India requires careful attention to local population demographics; one size may not fit all. A collaborative relationship between faith healers and mental health professionals could help with educational initiatives and to provide more accessible care. [Abstract copyright: Copyright © 2023. Published by Elsevier B.V.

The RhoGEF Trio Functions in Sculpting Class Specific Dendrite Morphogenesis in Drosophila Sensory Neurons

As the primary sites of synaptic or sensory input in the nervous system, dendrites play an essential role in processing neuronal and sensory information. Moreover, the specification of class specific dendrite arborization is critically important in establishing neural connectivity and the formation of functional networks. Cytoskeletal modulation provides a key mechanism for establishing, as well as reorganizing, dendritic morphology among distinct neuronal subtypes. While previous studies have established differential roles for the small GTPases Rac and Rho in mediating dendrite morphogenesis, little is known regarding the direct regulators of these genes in mediating distinct dendritic architectures.Here we demonstrate that the RhoGEF Trio is required for the specification of class specific dendritic morphology in dendritic arborization (da) sensory neurons of the Drosophila peripheral nervous system (PNS). Trio is expressed in all da neuron subclasses and loss-of-function analyses indicate that Trio functions cell-autonomously in promoting dendritic branching, field coverage, and refining dendritic outgrowth in various da neuron subtypes. Moreover, overexpression studies demonstrate that Trio acts to promote higher order dendritic branching, including the formation of dendritic filopodia, through Trio GEF1-dependent interactions with Rac1, whereas Trio GEF-2-dependent interactions with Rho1 serve to restrict dendritic extension and higher order branching in da neurons. Finally, we show that de novo dendritic branching, induced by the homeodomain transcription factor Cut, requires Trio activity suggesting these molecules may act in a pathway to mediate dendrite morphogenesis.Collectively, our analyses implicate Trio as an important regulator of class specific da neuron dendrite morphogenesis via interactions with Rac1 and Rho1 and indicate that Trio is required as downstream effector in Cut-mediated regulation of dendrite branching and filopodia formation

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Psychosocial skills training in schizophrenia: Process, outcome, and key influences

The efficacy of psychosocial skills training for individuals with serious mental illness has been well-documented. However, several questions remain regarding the course of, individual variability in response to, and predictors of response to skills training. The present study investigated course patterns during psychosocial skills training in individuals with serious mental illness. Five hypotheses were tested related to (a) the course of treatment progress during skills training, (b) relations between treatment progress and microprocess variables (e.g., attention), (c) identification of patient subgroups with varying amounts and rates of progress, (d) characterization of patient subgroups using pretreatment neurocognitive and social cognitive variables, and (e) examination of outcomes associated with subgroup membership. Archival clinical data from 93 individuals with serious mental illness at an inpatient psychiatric rehabilitation program in Nebraska was used. These individuals participated in a 9-week Medication Management skills training module developed at the University of California, Los Angeles. Results indicated that on average, participants improved over the course of skills training as assessed by a trainer-rated measure of treatment progress. There was significant inter-individual variation in progress ratings during the first week and over the course of skills training. Regarding relations with microprocess variables, treatment progress was strongly influenced by facilitating variables (attention, participation, and spontaneity). In contrast, hindering variables (withdrawal, disruption, and bizarre behavior) minimally impacted treatment progress. Three distinct treatment progress trajectories emerged: a low progress class ( n = 10), a moderate progress class (n = 61), and a high progress class (n = 22). Low progress class members differed from other class members in having poorer neurocognitive functioning at admission. The groups did not differ in social cognitive functioning at admission. Finally, the three classes differed in their likelihood of completing skills training and in post-treatment psychosocial functioning. Findings suggest that there is significant heterogeneity in the rate and magnitude of change during skills training. Psychosocial skills training programs should consider this heterogeneity and tailor interventions to particular patient subpopulations for optimal effectiveness