Tahilia J. Rebello

Postnatal Day 2 to 11 Constitutes a 5-HT-Sensitive Period Impacting Adult mPFC Function

Early-life serotonin [5-hydroxytryptamine (5-HT)] signaling modulates brain development, which impacts adult behavior, but 5-HT-sensitive periods, neural substrates, and behavioral consequences remain poorly understood. Here we identify the period ranging from postnatal day 2 (P2) to P11 as 5-HT sensitive, with 5-HT transporter (5-HTT) blockade increasing anxiety- and depression-like behavior, and impairing fear extinction learning and memory in adult mice. Concomitantly, P2–P11 5-HTT blockade causes dendritic hypotrophy and reduced excitability of infralimbic (IL) cortex pyramidal neurons that normally promote fear extinction. By contrast, the neighboring prelimbic (PL) pyramidal neurons, which normally inhibit fear extinction, become more excitable. Excitotoxic IL but not PL lesions in adult control mice reproduce the anxiety-related phenotypes. These findings suggest that increased 5-HT signaling during P2–P11 alters adult mPFC function to increase anxiety and impair fear extinction, and imply a differential role for IL and PL neurons in regulating affective behaviors. Together, our results support a developmental mechanism for the etiology and pathophysiology of affective disorders and fear-related behaviors.

Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction

Serotonin (5-HT)-selective reuptake inhibitors (SSRIs) are widely administered for the treatment of depression, anxiety, and other neuropsychiatric disorders, but response rates are low, and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs inhibit dopaminergic activity, but mechanistic insight remains scarce. Here we show that in mice, chronic 5-HT transporter (5-HTT) blockade during adulthood but not during development impairs basal ganglia-dependent behaviors in a dose-dependent and reversible fashion. Furthermore, chronic 5-HTT blockade reduces striatal dopamine (DA) content and metabolism. A causal relationship between reduced DA signaling and impaired basal ganglia-dependent behavior is indicated by the reversal of behavioral deficits through l-DOPA administration. Our data suggest that augmentation of DA signaling would reduce side effects and increase efficacies of SSRI-based therapy.

Innovative strategies for closing the mental health treatment gap globally.

Purpose of review In the field of global mental health, an enormous gap between what we know and what we do exists in the delivery of clinical care. Creative and effective strategies that surmount the barriers to provision of mental healthcare are essential to improve the lives of millions affected by mental illness. This article provides a review of three classes of innovative strategies currently being developed and implemented to diminish the mental health treatment gap globally. Recent findings This review provides recent evidence related to the feasibility of implementation and efficacy for the following three classes of innovation that show promise for building clinical capacity and expanding mental health coverage: integration of mental health services into primary care; expansion of human capacity through task sharing and training of nonspecialists; and innovative use of technological platforms to enhance access, cut costs, and reduce stigma. Summary The strategies outlined in this review hold great potential for enhancing mental health treatment services, and address some of the major barriers globally to accessing mental healthcare, such as scarcity of resources (infrastructure, capacity, and funding) and stigma. Despite much evidence supporting the efficacy of these models, thorough studies that test their feasibility, acceptability, utility, and effectiveness in various contexts, including low-income and middle-income countries, are required. Moreover, these innovations require social support and political will in order to be successfully implemented and scaled-up such that they have a meaningful impact on the burden of disease associated with mental illness worldwide.

Stigma-related mental health knowledge and attitudes among primary health workers and community health volunteers in rural Kenya

Background: The study was conducted in rural Kenya and assessed stigma in health workers from primary health facilities. Aims: This study compared variations in stigma-related mental health knowledge and attitudes between primary health workers (HWs) and community health volunteers (CHVs). Methods: Participants (n = 44 HWs and n = 60 CHVs) completed the self-report Mental Health Knowledge Schedule and the Reported and Intended Behavior Scale, along with sociodemographic questions. Multiple regression models were used to assess predictors of mental health knowledge and stigmatizing behaviors. Results: HWs had significantly higher mean mental health knowledge scores than CHVs, p < .001, and significantly higher mean positive attitudes scores than CHVs, p = .042. When controlling for relevant covariates, higher positive attitudes was the only significant predictor of higher mental health knowledge, and self-rating of sense of belonging to the community and mental health knowledge remained the main predictors of positive attitudes. Conclusion: Results suggest that stigma-related mental health knowledge and attitudes are associated, and interventions should target these areas with health workers. There is scope for intervention to increase knowledge and positive attitudes for individuals who feel a strong sense of community belonging. Future studies should test feasible ways to reduce stigma in this population.

The ICD-11 developmental field study of reliability of diagnoses of high-burden mental disorders: results among adult patients in mental health settings of 13 countries.

Reliable, clinically useful, and globally applicable diagnostic classification of mental disorders is an essential foundation for global mental health. The World Health Organization (WHO) is nearing completion of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD‐11). The present study assessed inter‐diagnostician reliability of mental disorders accounting for the greatest proportion of global disease burden and the highest levels of service utilization – schizophrenia and other primary psychotic disorders, mood disorders, anxiety and fear‐related disorders, and disorders specifically associated with stress – among adult patients presenting for treatment at 28 participating centers in 13 countries. A concurrent joint‐rater design was used, focusing specifically on whether two clinicians, relying on the same clinical information, agreed on the diagnosis when separately applying the ICD‐11 diagnostic guidelines. A total of 1,806 patients were assessed by 339 clinicians in the local language. Intraclass kappa coefficients for diagnoses weighted by site and study prevalence ranged from 0.45 (dysthymic disorder) to 0.88 (social anxiety disorder) and would be considered moderate to almost perfect for all diagnoses. Overall, the reliability of the ICD‐11 diagnostic guidelines was superior to that previously reported for equivalent ICD‐10 guidelines. These data provide support for the suitability of the ICD‐11 diagnostic guidelines for implementation at a global level. The findings will inform further revision of the ICD‐11 diagnostic guidelines prior to their publication and the development of programs to support professional training and implementation of the ICD‐11 by WHO member states.

Mentor Training within Academic Health Centers with Clinical and Translational Science Awards

Multiple studies highlight the benefits of effective mentoring in academic medicine. Thus, we sought to quantify and characterize the mentoring practices at academic health centers (AHCs) with Clinical and Translational Science Awards (CTSA). Here we report findings pertaining specifically to mentor training at the level of the KL2 mentored award program, and at the broader institutional level. We found only four AHCs did not provide any form of training. One‐time orientation was most prevalent at the KL2 level, whereas formal face‐to‐face training was most prevalent at the institutional level. Despite differences in format usage, there was general consensus at both the KL2 and institutional level about the topics of focus of face‐to‐face training sessions. Lower‐resource training formats utilized at the KL2 level may reveal a preference for preselection of qualified mentors, while institutional selection of resource‐heavy formats may be an attempt to raise the mentoring qualifications of the academic community as a whole. The present work fits into the expanding landscape of academic mentoring literature and sets the framework for future longitudinal, outcome studies focused on identifying the most efficient strategies to develop effective mentors.

Clinical utility of ICD-11 diagnostic guidelines for high-burden mental disorders: results from mental health settings in 13 countries: Clinical utility of ICD-11 diagnostic guidelines for high-burden mental disorders: results from mental health settings in 13 countries

In this paper we report the clinical utility of the diagnostic guidelines for ICD‐11 mental, behavioural and neurodevelopmental disorders as assessed by 339 clinicians in 1,806 patients in 28 mental health settings in 13 countries. Clinician raters applied the guidelines for schizophrenia and other primary psychotic disorders, mood disorders (depressive and bipolar disorders), anxiety and fear‐related disorders, and disorders specifically associated with stress. Clinician ratings of the clinical utility of the proposed ICD‐11 diagnostic guidelines were very positive overall. The guidelines were perceived as easy to use, corresponding accurately to patients’ presentations (i.e., goodness of fit), clear and understandable, providing an appropriate level of detail, taking about the same or less time than clinicians’ usual practice, and providing useful guidance about distinguishing disorder from normality and from other disorders. Clinicians evaluated the guidelines as less useful for treatment selection and assessing prognosis than for communicating with other health professionals, though the former ratings were still positive overall. Field studies that assess perceived clinical utility of the proposed ICD‐11 diagnostic guidelines among their intended users have very important implications. Classification is the interface between health encounters and health information; if clinicians do not find that a new diagnostic system provides clinically useful information, they are unlikely to apply it consistently and faithfully. This would have a major impact on the validity of aggregated health encounter data used for health policy and decision making. Overall, the results of this study provide considerable reason to be optimistic about the perceived clinical utility of the ICD‐11 among global clinicians.

Patterns of concordances in mhGAP-IG screening and DSM-IV/ICD10 diagnoses by trained community service providers in Kenya: a pilot cross-sectional study

PurposeThe objective of this study was to determine the extent of concordance between positive screens for mental disorders by various trained community-based health workers using the WHO mental health Gap Action Programme Intervention Guide (mhGAP-IG) and independently confirmed DSM-IV/ICD-10 diagnoses.MethodsThis was a cross-sectional study conducted in Makueni County, Kenya. 40 nurses/clinical officers, 60 Community Health Workers (CHWs), 51 Faith Healers (FHs), and 59 Traditional Healers (THs) from 20 facilities were trained to screen and refer patients with eight priority mental health conditions using the mhGAP-IG. These referrals, as well as referrals from friends or family members, and self-referrals were assessed using the Mini International Neuropsychiatric Instrument (M.I.N.I.) Plus. Concordance between positive screens and M.I.N.I. Plus diagnoses was investigated.Results15,078 community members agreed to participate in screening. Of these 12,170 (81%) screened positive for a mental disorder and were referred to their local clinics/hospitals. 8333 (68.5%) of those who were referred went for independent diagnostic assessment at the nearest facility. Positive predictive values varied with different providers and for different conditions. There was over 80% concordance between the initial screen and the M.I.N.I. Plus diagnoses across the different health providers and across all diagnoses.ConclusionBoth formal and informal mental health providers can be trained to successfully and accurately screen for mental health disorders using the mhGAP-IG symptoms. This suggests that community-based non-specialist providers may play a key role in decreasing the mental health treatment gap. Further policy implications are discussed.

A step-wise community engagement and capacity building model prior to implementation of mhGAP-IG in a low- and middle-income country: a case study of Makueni County, Kenya

BackgroundThe World Health Organization developed the Mental Health Gap Action Programme Intervention Guide (mhGAP-IG) as guidelines for innovative utilization of available resources in low- and middle-income countries (LMICs) in order to accelerate the reduction of the mental health treatment gap. The mhGAP-IG calls for each country to contextualize the guide to their social, cultural and economic context. The objective of this paper is to describe a model for a stepwise approach for implementation of mhGAP-IG in a rural Kenyan setting using existing formal and informal community resources and health systems.MethodsWe conducted an analysis of mental health services in Makueni County, one of the 47 counties in Kenya, in order to understand the existing gaps and opportunities in a low-resource setting. We conducted stakeholder analysis and engagement through interactive dialogue in order for them to appreciate the importance of mental health to their communities. Through the process of participatory Theory of Change, the stakeholders gave their input on the process between the initiation and the end of the process for community mental health development, with the aim of achieving buy-in and collective ownership of the whole process. We adapted the mhGAP-IG to the local context and trained local human resources in skills necessary for the implementation of mhGAP-IG and for monitoring and evaluating the process using instruments with good psychometric properties that have been used in LMICs.ResultsWe were able to demonstrate the feasibility of implementing the mhGAP-IG using existing and trained community human resources using a multi-stakeholder approach. We further demonstrated the feasibility to transit seamlessly from research to policy and practice uptake using our approach.ConclusionsAn inclusive model for low resource settings is feasible and has the potential to bridge the gap between research, policy and practice. A major limitation of our study is that we did not engage a health economist from the beginning in order to determine the cost-effectiveness of our proposed model, occasioned by lack of resources to hire a suitable one.

ICD-11 guidelines for psychotic, mood, anxiety and stress-related disorders in Mexico: Clinical utility and reliability

Background/Objective: The World Health Organizations diagnostic guidelines for ICD-11 mental and behavioural disorders must be tested in clinical settings around the world to ensure that they are clinically useful and genuinely global. The objective is evaluate the inter-rater reliability and clinical utility of ICD-11 guidelines for psychotic, mood, anxiety- and stress-related disorders in Mexican patients. Method: Adult volunteers exhibiting the selected symptoms were referred from the pre-consultation unit of a public psychiatric hospital to an interview by a pair of clinicians, who subsequently assigned independent diagnoses and evaluated the clinical utility of the diagnostic guidelines as applied to each particular case, on the basis of a scale developed for this purpose. Results: 23 clinicians evaluated 153 patients. Kappa scores were strong for psychotic disorders (.83), moderate for stress-related (.77) and mood disorders (.60) and week for anxiety and fear-related disorders (.43). A high proportion of clinicians considered all diagnostic guidelines to be quite to extremely useful as applied to their patients. Conclusions: ICD-11 guidelines for psychotic, stress-related and mood disorders allow adequate inter-rater consistency among Mexican clinicians, who also considered them as clinical useful tools.