生活習慣病とgenome-wide association study

Purpose of reviewThis article reviews the recent literature on reward processing dysfunction in major depression (MDD), bipolar disorder and schizophrenia, with a focus on approach motivation, reward learning and reward-based decision-making.Recent findingsEmerging evidence indicates the presence of

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Reward processing dysfunction in major depression, bipolar disorder and schizophrenia.

https://ir.library.oregonstate.edu/downloads/3j333418q

Zebrafish models for translational neuroscience research: from tank to bedside.

Thoroughly updated and completely reorganized for a sharper clinical focus, the Fifth Edition of this world-renowned classic synthesizes the latest advances in basic neurobiology, biological psychiatry, and clinical neuropsychopharmacology. The book establishes a critical bridge connecting new discoveries in molecular and cellular biology, genetics, and neuroimaging with the etiology, diagnosis, and treatment of the full spectrum of neuropsychiatric disorders.

Neuropsychopharmacology: The Fifth Generation of Progress

The relationship between mental and physical health: Insights from the study of heart rate variability

Context Bipolar mania and schizophrenia are recognized as separate disorders but share many commonalities, which raises the question of whether they are the same disorder on different ends of a continuum. The lack of distinct endophenotypes of bipolar mania and schizophrenia has complicated the development of animal models that are specific to these disorders. Exploration is fundamental to survival and is dysregulated in these 2 disorders. Although exploratory behavior in rodents has been widely studied, surprisingly little work has examined this critical function in humans. Objectives To quantify the exploratory behavior of individuals with bipolar mania and schizophrenia and to identify distinctive phenotypes of these illnesses. Design Static group comparison by the use of a novel human open field paradigm, the human Behavioral Pattern Monitor (BPM). Setting Psychiatric hospital. Participants Fifteen patients with bipolar mania and 16 patients with schizophrenia were compared with 26 healthy volunteers in the human BPM. The effects of amphetamine sulfate, the selective dopamine transporter inhibitor GBR12909, and the genetic knockdown of the dopamine transporter were compared with controls in the mouse BPM. Main Outcome Measures The amount of motor activity, spatial patterns of activity, and exploration of novel stimuli were quantified in both the human and mouse BPMs. Results Patients with bipolar mania demonstrated a unique exploratory pattern, characterized by high motor activity and increased object exploration. Patients with schizophrenia did not show the expected habituation of motor activity. Selective genetic or pharmacologic inhibition of the dopamine transporter matched the mania phenotype better than the effects of amphetamine, which has been the criterion standard for animal models of mania. Conclusions These findings validate the human open field paradigm and identify defining characteristics of bipolar mania that are distinct from those of schizophrenia. This cross-species study of exploration calls into question an accepted animal model of mania and should help to develop more accurate human and animal models, which are essential to the identification of the neurobiological underpinnings of neuropsychiatric disorders.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/210353/yoa90003_1072_1080.pdf

A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders: From Mice to Men

Heart rate variability in bipolar mania and schizophrenia.

A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders

Mania has long been recognized as aberrant behaviour indicative of mental illness Manic states include a variety of complex and multifaceted symptoms that challenge clear clinical distinctions Symptoms include over-activity, hypersexuality, irritability and reduced need for sleep, with cognitive deficits recently linked to functional outcome Current treatments have arisen through serendipity or from other disorders Hence, treatments are not efficacious for all patients, and there is an urgent need to develop targeted therapeutics Part of the drug discovery process is the assessment of therapeutics in animal models Here we review pharmacological, environmental and genetic manipulations developed to test the efficacy of therapeutics in animal models of mania The merits of these models are discussed in terms of the manipulation used and the facet of mania measured Moreover, the predictive validity of these models is discussed in the context of differentiating drugs that succeed or fail to meet criteria as approved mania treatments The multifaceted symptomatology of mania has not been reflected in the majority of animal models, where locomotor activity remains the primary measure This approach has resulted in numerous false positives for putative treatments Recent work highlights the need to utilize multivariate strategies to enable comprehensive assessment of affective and cognitive dysfunction Advances in therapeutic treatment may depend on novel models developed with an integrated approach that includes: (i) a comprehensive battery of tests for different aspects of mania, (ii) utilization of genetic information to establish aetiological validity and (iii) objective quantification of patient behaviour with translational cross-species paradigms

LINKED ARTICLES
This article is part of a themed issue on Translational Neuropharmacology To view the other articles in this issue visit http://dxdoiorg/101111/bph2011164issue-4

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.2011.01318.x

Brook L. Henry

Papers

A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders: From Mice to Men

Heart rate variability in bipolar mania and schizophrenia.

A Reverse-Translational Study of Dysfunctional Exploration in Psychiatric Disorders

Predictive animal models of mania: hits, misses and future directions

The quantitative assessment of motor activity in mania and schizophrenia.