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Translational Psychiatry

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https://www.readbyqxmd.com/read/28317470/anthropology-brokerage-and-collaboration-in-the-development-of-a-tongan-public-psychiatry-local-lessons-for-global-mental-health
#1
Mike Poltorak
The Global Mental Health (GMH) movement has raised questions of the translatability of psychiatric concepts and the challenges of community engagement. In Tonga, the local psychiatrist Dr Puloka successfully established a publicly accessible psychiatry that has improved admission rates for serious mental illnesses and addressed some of the stigma attached to diagnosis. On the basis of historical analysis and ethnographic fieldwork with healers, doctors, and patients since 1998, this article offers an ethnographic contextualization of the development and reception of Puloka's three key interventions during the 1990s: (a) collaboration with traditional healers; (b) translation of psychiatric diagnoses into local cultural concepts; and (c) encouraging freedom of movement and legal appeal to involuntary admission...
December 2016: Transcultural Psychiatry
https://www.readbyqxmd.com/read/28289275/epigenetic-programming-by-stress-and-glucocorticoids-along-the-human-lifespan
#2
A S Zannas, G P Chrousos
Psychosocial stress triggers a set of behavioral, neural, hormonal, and molecular responses that can be a driving force for survival when adaptive and time-limited, but may also contribute to a host of disease states if dysregulated or chronic. The beneficial or detrimental effects of stress are largely mediated by the hypothalamic-pituitary axis, a highly conserved neurohormonal cascade that culminates in systemic secretion of glucocorticoids. Glucocorticoids activate the glucocorticoid receptor, a ubiquitous nuclear receptor that not only causes widespread changes in transcriptional programs, but also induces lasting epigenetic modifications in many target tissues...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28283186/imaging-genetics-and-genomics-in-psychiatry-a-critical-review-of-progress-and-potential
#3
REVIEW
Ryan Bogdan, Betty Jo Salmeron, Caitlin E Carey, Arpana Agrawal, Vince D Calhoun, Hugh Garavan, Ahmad R Hariri, Andreas Heinz, Matthew N Hill, Andrew Holmes, Ned H Kalin, David Goldman
Imaging genetics and genomics research has begun to provide insight into the molecular and genetic architecture of neural phenotypes and the neural mechanisms through which genetic risk for psychopathology may emerge. As it approaches its third decade, imaging genetics is confronted by many challenges, including the proliferation of studies using small sample sizes and diverse designs, limited replication, problems with harmonization of neural phenotypes for meta-analysis, unclear mechanisms, and evidence that effect sizes may be more modest than originally posited, with increasing evidence of polygenicity...
January 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28277568/neurodevelopmental-perspectives-on-wnt-signaling-in-psychiatry
#4
REVIEW
Kimberly A Mulligan, Benjamin N R Cheyette
Mounting evidence indicates that Wnt signaling is relevant to pathophysiology of diverse mental illnesses including schizophrenia, bipolar disorder, and autism spectrum disorder. In the 35 years since Wnt ligands were first described, animal studies have richly explored how downstream Wnt signaling pathways affect an array of neurodevelopmental processes and how their disruption can lead to both neurological and behavioral phenotypes. Recently, human induced pluripotent stem cell (hiPSC) models have begun to contribute to this literature while pushing it in increasingly translational directions...
February 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/28242871/attenuation-of-ketamine-induced-impairment-in-verbal-learning-and-memory-in-healthy-volunteers-by-the-ampa-receptor-potentiator-pf-04958242
#5
M Ranganathan, N DeMartinis, B Huguenel, F Gaudreault, M M Bednar, C L Shaffer, S Gupta, J Cahill, M A Sherif, J Mancuso, L Zumpano, D C D'Souza
There is a need to develop treatments for cognitive impairment associated with schizophrenia (CIAS). The significant role played by N-methyl-d-aspartate receptors (NMDARs) in both the pathophysiology of schizophrenia and in neuronal plasticity suggests that facilitation of NMDAR function might ameliorate CIAS. One strategy to correct NMDAR hypofunction is to stimulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as AMPAR and NMDAR functioning are coupled and interdependent. In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caused by the nonselective NMDAR antagonist ketamine...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28236988/-what-can-we-expect-from-clinical-trials-in-psychiatry
#6
A Marsot, Q Boucherie, F Kheloufi, C Riff, D Braunstein, J Dupouey, R Guilhaumou, X Zendjidjian, S Bonin-Guillaume, E Fakra, M Guye, V Jirsa, J-M Azorin, R Belzeaux, M Adida, J Micallef, O Blin
Clinical trials in psychiatry allow to build the regulatory dossiers for market authorization but also to document the mechanism of action of new drugs, to build pharmacodynamics models, evaluate the treatment effects, propose prognosis, efficacy or tolerability biomarkers and altogether to assess the impact of drugs for patient, caregiver and society. However, clinical trials have shown some limitations. Number of recent dossiers failed to convince the regulators. The clinical and biological heterogeneity of psychiatric disorders, the pharmacokinetic and pharmacodynamics properties of the compounds, the lack of translatable biomarkers possibly explain these difficulties...
December 2016: L'Encéphale
https://www.readbyqxmd.com/read/28194682/psychopharmacology-prescribing-workshops-a-novel-method-for-teaching-psychiatry-residents-how-to-talk-to-patients-about-medications
#7
Eileen P Kavanagh, John Cahill, Melissa R Arbuckle, Alison E Lenet, Kalyani Subramanyam, Ronald M Winchel, Ilana Nossel, Ravi DeSilva, Rachel A Caravella, Marra Ackerman, Henry C Park, David A Ross
OBJECTIVE: Traditional, lecture-based methods of teaching pharmacology may not translate into the skills needed to communicate effectively with patients about medications. In response, the authors developed an interactive course for third-year psychiatry residents to reinforce prescribing skills. METHODS: Residents participate in a facilitated group discussion combined with a role-play exercise where they mock-prescribe medication to their peers. Each session is focused on one medication or class of medications with an emphasis on various aspects of informed consent (such as describing the indication, dosing, expected benefits, potential side effects, and necessary work-up and follow up)...
February 13, 2017: Academic Psychiatry
https://www.readbyqxmd.com/read/28167743/validation-of-a-risk-stratification-tool-for-fall-related-injury-in-a-state-wide-cohort
#8
Thomas H McCoy, Victor M Castro, Andrew Cagan, Ashlee M Roberson, Roy H Perlis
OBJECTIVE: A major preventable contributor to healthcare costs among older individuals is fall-related injury. We sought to validate a tool to stratify such risk based on readily available clinical data, including projected medication adverse effects, using state-wide medical claims data. DESIGN: Sociodemographic and clinical features were drawn from health claims paid in the state of Massachusetts for individuals aged 35-65 with a hospital admission for a period spanning January-December 2012...
February 6, 2017: BMJ Open
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#9
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28089652/hippocampal-prefrontal-connectivity-as-a-translational-phenotype-for-schizophrenia
#10
REVIEW
Florian Bähner, Andreas Meyer-Lindenberg
Finding novel biological targets in psychiatry has been difficult, partly because current diagnostic categories are not defined by pathophysiology and difficult to model in animals. The study of species-conserved systems-level mechanisms implicated in psychiatric disease could be a promising strategy to address some of these difficulties. Altered hippocampal-prefrontal (HC-PFC) connectivity during working memory (WM) processing is a candidate for such a translational phenotype as it has been repeatedly associated with impaired cognition in schizophrenia patients and animal models for psychiatric risk factors...
February 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28089559/microglia-derived-neuregulin-expression-in-psychiatric-disorders
#11
Daisuke Ikawa, Manabu Makinodan, Keiko Iwata, Masahiro Ohgidani, Takahiro A Kato, Yasunori Yamashita, Kazuhiko Yamamuro, Sohei Kimoto, Michihiro Toritsuka, Takahira Yamauchi, Shin-Ichi Fukami, Hiroki Yoshino, Kazuki Okumura, Tatsuhide Tanaka, Akio Wanaka, Yuji Owada, Masatsugu Tsujii, Toshiro Sugiyama, Kenji Tsuchiya, Norio Mori, Ryota Hashimoto, Hideo Matsuzaki, Shigenobu Kanba, Toshifumi Kishimoto
Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD...
January 10, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28076638/the-future-of-psychiatric-research
#12
Marco Antonio Caldieraro
Psychiatric disorders place considerable burden on individuals and on public health. Funding for research in psychiatry is less than ideal, but even so high quality research is being conducted at many centers. However, these studies have not impacted clinical practice as much as expected. The complexity of psychiatric disorders is one of the reasons why we face difficulties in translating research results to patient care. New technologies and improved methodologies are now available and must be incorporated to deal with this complexity and to accelerate the translational process...
October 2016: Trends in Psychiatry and Psychotherapy
https://www.readbyqxmd.com/read/28044063/molecular-mechanisms-underlying-noncoding-risk-variations-in-psychiatric-genetic-studies
#13
REVIEW
X Xiao, H Chang, M Li
Recent large-scale genetic approaches such as genome-wide association studies have allowed the identification of common genetic variations that contribute to risk architectures of psychiatric disorders. However, most of these susceptibility variants are located in noncoding genomic regions that usually span multiple genes. As a result, pinpointing the precise variant(s) and biological mechanisms accounting for the risk remains challenging. By reviewing recent progresses in genetics, functional genomics and neurobiology of psychiatric disorders, as well as gene expression analyses of brain tissues, here we propose a roadmap to characterize the roles of noncoding risk loci in the pathogenesis of psychiatric illnesses (that is, identifying the underlying molecular mechanisms explaining the genetic risk conferred by those genomic loci, and recognizing putative functional causative variants)...
January 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28044059/the-esc-e-z-complex-an-effector-of-response-to-ovarian-steroids-manifests-an-intrinsic-difference-in-cells-from-women-with-premenstrual-dysphoric-disorder
#14
N Dubey, J F Hoffman, K Schuebel, Q Yuan, P E Martinez, L K Nieman, D R Rubinow, P J Schmidt, D Goldman
Clinical evidence suggests that mood and behavioral symptoms in premenstrual dysphoric disorder (PMDD), a common, recently recognized, psychiatric condition among women, reflect abnormal responsivity to ovarian steroids. This differential sensitivity could be due to an unrecognized aspect of hormonal signaling or a difference in cellular response. In this study, lymphoblastoid cell line cultures (LCLs) from women with PMDD and asymptomatic controls were compared via whole-transcriptome sequencing (RNA-seq) during untreated (ovarian steroid-free) conditions and following hormone treatment...
January 3, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28032396/computational-neuroscience-approach-to-biomarkers-and-treatments-for-mental-disorders
#15
Noriaki Yahata, Kiyoto Kasai, Mitsuo Kawato
Psychiatry research has long experienced a stagnation stemming from a lack of understanding of the neurobiological underpinnings of phenomenologically defined mental disorders. Recently, the application of computational neuroscience to psychiatry research has shown great promise in establishing a link between phenomenological and pathophysiological aspects of mental disorders, thereby recasting current nosology in more biologically meaningful dimensions. In this review, we highlight recent investigations in computational neuroscience that undertook either theory- or data-driven approaches to quantitatively delineate the mechanisms of mental disorders...
December 29, 2016: Psychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/27956743/translational-profiling-of-stress-induced-neuroplasticity-in-the-ca3-pyramidal-neurons-of-bdnf-val66met-mice
#16
J D Gray, T G Rubin, J F Kogan, J Marrocco, J Weidmann, S Lindkvist, F S Lee, E F Schmidt, B S McEwen
Genetic susceptibility and environmental factors (such as stress) can interact to affect the likelihood of developing a mood disorder. Stress-induced changes in the hippocampus have been implicated in mood disorders, and mutations in several genes have now been associated with increased risk, such as brain-derived neurotrophic factor (BDNF). The hippocampus has important anatomical subdivisions, and pyramidal neurons of the vulnerable CA3 region show significant remodeling after chronic stress, but the mechanisms underlying their unique plasticity remain unknown...
December 13, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27927173/reliability-validity-and-factorial-structure-of-the-arabic-version-of-the-international-suicide-prevention-trial-intersept-scale-for-suicidal-thinking-in-schizophrenia-patients-in-doha-qatar
#17
Samer Hammoudeh, Suhaila Ghuloum, Ziyad Mahfoud, Mark Opler, Anzalee Khan, Arij Yehya, Abdulmoneim Abdulhakam, Azza Al-Mujalli, Yahya Hani, Reem Elsherbiny, Hassen Al-Amin
BACKGROUND: Patients with schizophrenia are known to have higher rates of mortality and morbidity when compared to the general population. Suicidality is a major contributor to increased mortality. The International Suicide Prevention Trial (InterSePT) Scale for Suicidal Thinking (ISST) is a validated tool to assess current suicidal ideation in patients with schizophrenia. The aims of the study were to culturally adapt the Arabic translation of ISST and to examine the psychometric characteristics of the Arabic version of the ISST among patients with schizophrenia in Qatar...
December 7, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27895323/elevated-cyp2c19-expression-is-associated-with-depressive-symptoms-and-hippocampal-homeostasis-impairment
#18
M M Jukić, N Opel, J Ström, T Carrillo-Roa, S Miksys, M Novalen, A Renblom, S C Sim, E M Peñas-Lledó, P Courtet, A Llerena, B T Baune, D J de Quervain, A Papassotiropoulos, R F Tyndale, E B Binder, U Dannlowski, M Ingelman-Sundberg
The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype...
November 29, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27878323/assessing-needs-for-psychiatric-treatment-in-prisoners-2-met-and-unmet-need
#19
Sharon Jakobowitz, Paul Bebbington, Nigel McKenzie, Rachel Iveson, Gary Duffield, Mark Kerr, Helen Killaspy
BACKGROUND: In a companion paper, we established high levels of psychiatric morbidity in prisoners (Bebbington et al. Soc Psychiatry Psychiatr Epidemiol, 2016). In the current report, we evaluate how this morbidity translates into specific needs for treatment and the consequent implications for services. Mental health treatment needs and the extent to which they had been met were assessed in a representative sample of prisoners in a male and a female prison in London (Pentonville and Holloway)...
February 2017: Social Psychiatry and Psychiatric Epidemiology
https://www.readbyqxmd.com/read/27856767/suicidal-thinking-and-behaviour-as-of-600-bce-aesop-s-fables
#20
Julian Davis, Tammie T Money, Saxby Pridmore
OBJECTIVE: Psychiatry has ignored history, anthropology, sociology and literature in the search for enlightenment regarding suicide. Our objective was to determine what, if anything, Aesop's fables had to teach us about suicide in around 600 BCE. Aesop's account is around two centuries older than the oldest text (Herodotus: The histories) previously examined by our group. METHOD: We examined two translations of Aesop's fables, seeking accounts fitting the following categories: (1) suicidal thinking, (2) suicidal behaviour without fatal consequences, and (3) suicidal behaviour with fatal consequences...
November 17, 2016: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
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