Grand challenges in global mental health

Collins, Pamela Y.; Patel, Vikram; Joestl, Sarah S.; March, Dana; Insel, Thomas R.; Daar, Abdallah S.; Bordin, Isabel Altenfelder Santos; Costello, E. Jane; Durkin, Maureen S.; Fairburn, C. G.; Glass, Roger I.; Hall, Wayne; Huang, Yueqin; Hyman, Steven E.; Jamison, Kay Redfield; Kaaya, Sylvia; Kapur, Shitij; Kleinman, Arthur; Ogunniyi, Adesola; Otero-Ojeda, Angel A.; Poo, Mu‐ming; Ravindranath, Vijayalakshmi; Sahakian, Barbara J.; Saxena, Shekhar; Сингер, Петер; Stein, Dan J.; Anderson, Warwick P.; Dhansay, Muhammad A.; Ewart, Wendy; Phillips, Anthony G.; Shurin, Susan B.; Walport, Mark J.

doi:10.1038/475027a

Cited by 1,717 publications

(1,248 citation statements)

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“…Stress-related neuropsychiatric disorders, such as major depressive disorder (MDD) and generalized anxiety disorder (GAD), are among the most significant contributors to global disease burden (Collins et al, 2011). Current treatments are often inadequate (Mojtabai, 2009;Wittchen et al, 2011), in large part due to the related issues that each disorder comprises heterogeneous groups of symptoms (DSM-5, 2013) and their aetiopathophysiologies are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase

Fuertig

Azzinnari

Bergamini

et al. 2016

Brain, Behavior, and Immunity

117

125

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Psychosocial stress is a major risk factor for mood and anxiety disorders, in which excessive reactivity to aversive events/stimuli is a major psychopathology. In terms of pathophysiology, immuneinflammation is an important candidate, including high blood and brain levels of metabolites belonging to the kynurenine pathway. Animal models are needed to study causality between psychosocial stress, immune-inflammation and hyper-reactivity to aversive stimuli. The present mouse study investigated effects of psychosocial stress as chronic social defeat (CSD) versus control-handling (CON) on: Pavlovian tone-shock fear conditioning, activation of the kynurenine pathway, and efficacy of a specific inhibitor (IDOInh) of the tryptophan-kynurenine catabolizing enzyme indoleamine 2,3-dioxygenase (IDO1), in reversing CSD effects on the kynurenine pathway and fear. CSD led to excessive fear learning and memory, whilst repeated oral escitalopram (antidepressant and anxiolytic) reversed excessive fear memory, indicating predictive validity of the model. CSD led to higher blood levels of TNF-, IFN-, kynurenine (KYN), 3-hydroxykynurenine (3-HK) and kynurenic acid, higher KYN and 3-HK in amygdala and hippocampus. However, CSD was without effect on IDO1 gene or protein expression in spleen, ileum and liver, whilst increasing liver TDO2 gene expression. Nonetheless, oral IDOInh reduced blood and brain levels of KYN and 3-HK in CSD mice to CON levels, and we therefore infer that CSD increases IDO1 activity by increasing its post-translational activation. Furthermore, repeated oral IDOInh reversed excessive fear memory in CSD mice to CON levels. IDOInh reversal of CSD-induced hyper-activity in the kynurenine pathway and fear system contributes significantly to the evidence for a causal pathway between psychosocial stress, immune-inflammation and the excessive fearfulness that is a major psychopathology in stress-related neuropsychiatric disorders. ABSTRACTPsychosocial stress is a major risk factor for mood and anxiety disorders, in which excessive reactivity to aversive events/stimuli is a major psychopathology. In terms of pathophysiology, immune-inflammation is an important candidate, including high blood and brain levels of metabolites belonging to the kynurenine pathway. Animal models are needed to study causality between psychosocial stress, immune-inflammation and hyper-reactivity 3-HK in CSD mice to CON levels, and we therefore infer that CSD increases IDO1 activity by increasing its post-translational activation. Furthermore, repeated oral IDOInh reversed excessive fear memory in CSD mice to CON levels. IDOInh reversal of CSD-induced hyperactivity in the kynurenine pathway and fear system contributes significantly to the evidence for a causal pathway between psychosocial stress, immune-inflammation and the excessive fearfulness that is a major psychopathology in stress-related neuropsychiatric disorders.3

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Section: Introductionmentioning

confidence: 99%

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase

Fuertig

Azzinnari

Bergamini

et al. 2016

Brain, Behavior, and Immunity

117

125

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“…There is also evidence demonstrating that PT developed in Western cultural contexts retain their effectiveness in different cultural contexts, when adapted following a systematic methodology (Chowdhary et al., 2013). A key Grand Challenge in Global Mental Health is to design a methodology for the development and evaluation of PT by lay counselors (Collins et al., 2011). …”

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confidence: 99%

The Systematic Development and Pilot Randomized Evaluation of Counselling for Alcohol Problems, a Lay Counselor‐Delivered Psychological Treatment for Harmful Drinking in Primary Care in India: The PREMIUM Study

Nadkarni

Velleman

Dabholkar³

et al. 2015

Alcohol Clin Exp Res

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BackgroundDespite harmful drinking causing a significant burden on global health, there is a large treatment gap, especially in low‐ and middle‐income countries. A major barrier to care is the lack of adequately skilled human resources to deliver contextually appropriate treatments. This paper describes the systematic process used to develop Counselling for Alcohol Problems (CAP), a brief psychological treatment (PT) for delivery by lay counselors in routine primary care settings to men with harmful drinking in India.MethodsCAP was developed using a methodology involving 3 sequential steps: (i) identifying potential treatment strategies; (ii) developing a theoretical framework for the treatment; and (iii) evaluating the acceptability and feasibility of the treatment.ResultsCAP is a 3‐phase treatment delivered over 1 to 4 sessions based on a motivational interviewing (MI) stance and involves the following strategies: assessment and personalized feedback, family engagement, drink refusal skills, skills to address drinking urges, problem‐solving skills and handling difficult emotions, and relapse prevention and management. Data from a case series were used to inform several adaptations to enhance the acceptability of CAP to the recipients and feasibility of delivery by lay counselors of the treatment, for example expansion of the target group to include alcohol‐dependent patients and the extension of the delivery settings to include home‐based delivery. There was preliminary evidence of the effectiveness of CAP.ConclusionsCAP is an acceptable brief PT for harmful drinking delivered by lay counselors in primary care whose effectiveness is currently being tested in a randomized controlled trial based in primary care in Goa, India.

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“…burden, mental disorders have exceeded diseases of the cardiovascular and respiratory systems as well as malignant tumors [1] . Nevertheless, the pathological mental activities caused by the millions of neurons in the human brain are far less clear than diseases of other organs and systems.…”

mentioning

confidence: 99%

An update on research and approaches in biological psychiatry

2015

Neurosci. Bull.

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Grand challenges in global mental health

Cited by 1,717 publications

References 11 publications

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase

Mouse chronic social stress increases blood and brain kynurenine pathway activity and fear behaviour: Both effects are reversed by inhibition of indoleamine 2,3-dioxygenase

The Systematic Development and Pilot Randomized Evaluation of Counselling for Alcohol Problems, a Lay Counselor‐Delivered Psychological Treatment for Harmful Drinking in Primary Care in India: The PREMIUM Study

An update on research and approaches in biological psychiatry

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