癌症与精神病人亲属心身状况及改善对策的跨文化探讨

目的研究居澳华裔及国内癌症及精神病人亲属的健康状况。方法以深层面谈和电话会谈、问卷法调查居澳华裔、居国内的癌症和精神病患者及其亲属共288人。结果绝大部分亲属有不同程度的焦虑、抑郁，伴有失眠、疲劳、衰弱等症状。2.78％～11．11‰被诊断为焦虑症、抑郁症或各种心身疾病。癌症病人亲属的健康状况随病人病情的波动而变化；精神病人亲属的健康状况随病人病情的进展和时间的推移趋向稳定。国内组与澳洲组表现有一定的差别。他们希望有完善的机构与设施帮助照顾其患病的亲人。结论建立完善的机构为癌症及精神病患者提供照顾等服务，帮助其亲属进行有效的心理调节，保持心身健康，是21世纪的国际性课题之一。

Scientific Interest of Social Behaviour in Animal Models of Human Diseases

The overview shows that the scientific interest in social behaviour in mice has exponentially grown in the last two decades in parallel with advances in biotechnology and the emergence of genetically engineered mice. Most of the studies are psychopharmacological or look for the neurochemical bases of social behaviour and its alterations. However, the rol of social behaviour per se is increasing mainly in those research works aimed to model neuropsychiatric and neurode-generative diseases. In fact, at the translational level, the study of social behaviour in murine models is relevant because changes in social behaviour are present in most neuropsychiatric and neurodegenerative disorders as well as in other diseases that, directly or indirectly, affect the sphere of social relationships. The consideration of social behaviour in the experimental design of basic and translational research works using murine models may improve the predictive validity of new preventive and/or therapeutic strategies. The present work provides conceptual description of social behaviour in mice, the tests used to measure it and analyzes its increasing interest, mostly in the area of neuroscience. It reviews the 821 scientific studies (in English) included in the MEDLINE database from 1930 to December 2012. Keywords used for the search where those related to the different kinds of social behaviour (spontaneous or induced) in mice and took into account the diversity of experimental paradigms (dyads, groups, parental relationships, isolation) and the wide spectrum of behavioural tests available.

Identification of Genetic Variants Underlying Anxiety and Multiple Sclerosis in Heterogeneous Stock Rats

Identifying genetic variants that contribute to phenotypic variation is expected to provide insights into the etiology of complex traits. Here we show how combining genetic mapping in an outbred population of rats with sequence data from the progenitors of the population made it possible to identify causal variants and genes for a large number of phenotypes. We identified 355 genomic loci contributing to 122 measures relevant to six models of disease, including fear-related behaviors and experimental autoimmune encephalomyelitis. At 35 of those loci we identified the responsible gene, and in some cases, the responsible variant.

Genetic Rat Models of Schizophrenia-Relevant Symptoms

It is recognized that developing valid animal models is essential for the research on the neurobiological mechanisms of (and treatments for) psychiatric disorders, even when these are as complex as schizophrenia. To be considered a valid analogue of the disorder, a given model should present good face validity (i.e. similarity of symptoms), good predictive validity (i.e. similarity of treatment effects and potential for discovering novel treatments) and enough construct validity (i.e. the model should help discover neurobiological mechanisms underlying the disorder or some relevant symptoms). The complexity of symptoms (positive, negative and cognitive) of schizophrenia makes it a very difficult task for a model to mimic all the main features of the disorder, but some rodent (mouse and rat) models have behavioural and even neurobiological phenotype characteristics resembling positive-like symptoms, cognitive symptoms and some neurochemical features of schizophrenia. As several recent works have already reviewed the main behavioural and developmental models, as well as the most used drug-induced, lesion-induced and genetic mouse models, the present review focuses on describing the most relevant genetically-based rat models of schizophrenia-relevant symptoms. Thus, we discuss several selective breeding programs leading to rat lines/strains which present impaired prepulse inhibition (PPI) of the acoustic startle response and (in some cases) latent inhibition deficits (both of which may be considered as endophenotypes of schizophrenia related with pre-attentive processes and attention, respectively), as well as other schizophrenia-relevant symptoms (e.g. learning deficits). Evidence is presented for the effects of genetic background on PPI (and other symptoms/phenotypes), as well as for environmental influences on genetic predisposition to enhanced apomorphine (mixed dopamine receptor agonist) effects. Some of the described rat models appear to present face validity and, to a certain extent, construct validity. While efforts should be made to evaluate the predictive validity of these genetic rat models, we propose that they have the advantage (over mouse knockouts, for example) of better representing “normal” genetic, neurobiological and phenotype variation, thus allowing the study of associations among them by means of genetic mapping or gene expression studies.

Helplessness-like escape deficits of NIH-HS rats predict passive behavior in the forced swimming test:Relevance for the concurrent validity of rat models of depression

The genetically heterogeneous NIH-HS rat stock has been characterized by its response to anxiety- and fear-inducing situations, thus leading to the conclusion that they are a rather anxious and passive coping type of rats. Taking advantage of these profiles, and knowing that they show very poor performance in the two-way active (shuttle box) escape/avoidance task, we have tested NIH-HS rats (n = 80) in the forced swimming test (FST) as well as we have studied escape response deficits (i.e. response failures) of the same animals in the two-way shuttle box task. They were also tested for anxiety in the elevated zero-maze. The goal of such a study was that of investigating whether there are associations or relationships among helplessness-like or passive coping responses between both models of depression, i.e. the FST and the helplessness-like escape deficits in the shuttle box task. The results for the first time show associations among responses from both depression models and that selecting rats for displaying extreme (active or passive) responses in one of the models predict in a coherent manner (according to the hypothesis) their behaviour in the other model. These findings are discussed in the context of the concurrent validity of both models of depression as well as concerning the possible relevance of NIH-HS rats as a tool for future studies on this field.

What can we learn on rodent fearfulness/anxiety from the genetically heterogeneous NIH-HS rat stock?

The “National Institutes of Health” genetically heterogeneous (NIH-HS) rat stock was created in the 1980s through an eight-way cross of as much as possible separate inbred rat strains (i.e. the MR/N, WN/N, WKY/N, M520/N, F344/N, ACI/N, BN/SsN and BUF/N strains) which were readily available at that time. Hansen and Spuhler [1] developed a more naturalistic, genetically heterogeneous rat stock with the aim of optimizing the distribution of genotypic frequencies and recombination and under the hypothesis that the NIH-HS stock could yield a broad-range distribution of responses (broader than commonly used laboratory rat strains) to experimental conditions, and thus serve as a base population for selection studies. Along the last decade, in a series of studies we have phenotypically characterized the NIH-HS rat stock (a colony exists at our laboratory since 2004) for their anxiety/fearfulness profiles (using a battery of both unconditioned and conditioned tests/tasks), as well as regarding their stress-induced hormonal responses, coping style under inescapable stress and spatial learning ability. We have also compared the phenotypic profiles of NIH-HS rats with those of the low anxious RHA-I and the high anxious RLA-I rat strains. The NIH-HS rat stock is, as a population, a rather anxious type of rat, with predominantly reactive/passive coping style in unlearned and learned anxiety/fear tests, and elevated stress hormone responses (as well as enhanced “depressive” symptoms in the forced swimming test). Genetic studies currently under way have thus far revealed that the genetically heterogeneous NIH-HS rat stock constitutes a unique tool for fine mapping of QTL (for multiple behavioural and biological complex traits) to megabase resolution levels, thus enabling candidate gene identification. We give some examples of this in the present paper, while also highlighting that microarray gene expression studies reveal that HPA-axis- and prolactin-related genes (among others) in the amygdala appear to be related with (or associated to) the coping style and anxiety/fearfulness responses of NIH-HS rats.

Relationships of open-field behaviour with anxiety in the elevated zero-maze test:Focus on freezing and grooming

The National Institutes of Health Genetically Heterogeneous Rat Stock (NIH-HS) is a unique tool for genetic studies of complex traits due to its high genetic heterogeneity and to its high level of genetic recombinants accumulated along many outbreeding generations. In the present study, 90 NIH-HS male rats were tested for anxiety/fearfulness in the elevated zero-maze and in the open-field test in order to investigate the associations among defensive responses from both tests and, in particular, those among open- field self-grooming and freezing. These associations were evaluated by means of a correlational-factorial approach and an analysis of differences between sub- groups displaying extreme scores in representative variables. The final factor analysis revealed a first factor with high loadings of all variables from the zero-maze (“Maze timidity/conflict” factor), and a second (independent) factor dominated by open-field crossings (-0.74), rearings (-0.62) and freezing (0.65), with lower loadings of open-field grooming (-0.39) and stretched attend postures, as well as of entries and time (loadings of -0.32 to -0.25) in the open sections of the zero-maze (“Open Behavior inhibition/ desinhibition” factor), suggesting that open-field self-grooming is a response associated to activity, in the present study, rather than to inhibition. Furthermore, the finding that grooming in the OF loaded negatively in a second factor supports a relationship between grooming and dearousal. Present results, thus, are in accordance with the usefulness of these tests for the purposes they are commonly employed and add new evidence supporting their concurrent validity, as indicated by the relationships observed among measures from both tests.