功能性影像技术在抑郁症研究中的进展

近些年来，正电子发射计算机断层扫描（ＰＥＴ）和单光子发射计算机断层扫描（ＳＰＥＣＴ），在情感性精神障碍患者脑血流和代谢方面的研究较多。与计算机断层扫描（ＣＴ）和磁共振（ＭＲＩ）比较，ＳＰＥＣＴ和ＰＥＴ通过对活体大脑血流及神经化学活动进行动态观察，取得...     

生物芯片技术及其在精神疾病研究中的应用

本文介绍了生物芯片技术的基本情况及近年基因芯片在精神疾病的实验室研究中应用的进展。     

功能性磁共振在精神疾病中的临床应用

应用功能性磁共振研究精神疾病近几年的报道日渐增多,该技术可以研究脑高级认知功能。有关功能性磁共振原理非常复杂,在精神疾病应用范围较广,尽管目前该技术尚存在一定局限性,但其作为目前唯一活体可以无创检测人体脑功能的技术已经显示出相当的优越性。     

生物芯片技术及其在精神疾病研究中的应用

本文介绍了生物芯片技术的基本情况及近年基因芯片在精神疾病的实验室研究中应用的进展。     

基因芯片在精神疾病研究中的应用

介绍基因芯片技术的基本情况及近年来在精神分裂症、阿尔茨海默病及其他精神疾病易感基因的研究中应用进展。     

影像基因组学在精神疾病研究中的应用

认识复杂认知及情感行为的生物学机制，对我们理解行为差异及精神疾病易患性的个体差异非常重要。分子遗传学、非侵入性的功能神经影像学的发展，为我们探讨认知和行为的生物学机制提供了必要工具。人类基因序列图谱的绘制完成，为人类认识功能基因序列的常见变异以及进一步了解这些变异改变人的生物学特性提供了巨大帮助。由于约70％的基闲在大脑中表达，其塔因功能多态性多数影响大脑的信息处理过程。因功能神经影像[如单光子发射断层摄影术（PET）、功能磁共振成像（fMRI）、腩磁图（MEG）]能在体评定个体的不同脑区的信息处理过程，已成为惟一能够测定大脑功能基因组学特征的工具。现就影像基因组学的概念、作用原理及最新进展综述于下。[第一段]     

PET脑代谢显像与SPECT脑血流灌注显像在癫痫灶定位中的应用

目的 探讨PET显像与SPECT显像在顽固性癫痫灶定位中的应用价值.方法 86例癫痫患者均行发作间期PET和SPECT显像,36例发作间期PET结果为多灶改变(包括15例存在脑软化灶)的患者行发作期SPECT检查,结果分析采用半定量分析及目测法.结果 86例患者均见不同程度异常改变.发作间期PET显像示低代谢者中50例(58.1％)表现为单叶局限性低代谢,发作间期SPECT显像示低灌注者中48例(55.8％)表现为单叶局限性低灌注.对36例发作间期PET结果为多灶改变的患者行发作期SPECT检查示,35例(97.2％)例高灌注灶,高灌注中24例(68.6％)为单叶局限性高灌注,5例(14.2％)仍见多个病灶,但未见弥漫性高灌注.1例(2.8％)未发现高灌注区.15例(41.7％)脑软化灶患者经发作期SPECT检查后均定位为局限性病灶,且在脑软灶边缘.结论 发作间期PET显像与发作间期SPECT定位局限性单叶癫痫病灶的符合率较高,两者相互印证可提高特异性;发作间期PET检出多灶性改变时,结合发作期SPECT显像可提高定位特异性.存在脑软化灶病例行PET检查意义较小,进行发作间期及发作期SPECT两次显像即可较好的定位病灶.     

托吡酯在精神疾病治疗中的应用

本文对托吡酯在双相情感性精神障碍、癫痫伴精神障碍、Tourette综合征、暴食性障碍、氯氮平所致癫痫发作治疗中的应用情况作一介绍。托吡酯具有药物相互作用及副作用相对较少 ,患者对治疗的依从性较高等优点 ,今后若能进一步验证其疗效 ,则有可能为许多精神疾病的治疗提供新的手段。     

功能磁共振成像在精神疾病中的应用

功能磁共振成像(fMRI)已广泛应用于精神疾病的科研与临床,该技术能较方便地观察到脑功能活动,从而帮助研究者更深入地探索疾病的病因、发病机制、诊断及治疗。本文就近年fMRI在精神疾病中的应用做一综述,为精神医学的科研和临床提供参考。     

探究性眼球运动轨迹在精神疾病中的应用

探究性眼球运动（exploratory eye movement，EEM）是通过记录受试者在随意注意静止图像时出现的眼球运动轨迹。目前其在精神疾病中的应用范围较局限，现作一综述。     

Novel animal models of affective disorders

Is there an appropriate animal model for human affective disorders? The traditional difficulties in accepting animal models for psychopathology stem from the argument that there is no evidence for concluding that what occurs in the brain of the animal is equivalent to what occurs in the brain of a human. However, if one models any or some core aspects of affective disorder, this model can become an invaluable tool in the analysis of the multitude of causes, genetic, environmental, or pharmacological, that can bring about symptoms homologous to those of patients with affective disorders. Animal models can also allow the study of the mechanisms of specific behaviors, their pathophysiology, and can aid in developing and predicting therapeutic responses to pharmacologic agents. Although animals exhibit complex and varied social and emotional behaviors for which well-validated and standardized measures exist, an understanding that a precise replica of human affective disorders cannot be expected in a single animal model is crucial. Instead, a good animal model of a human disorder should fulfill as many of the four main criteria as possible: (1) strong behavioral similarities, (2) common cause, (3) similar pathophysiology, and (4) common treatment. An animal model fulfilling any or most of these criteria can be used to elucidate the mechanisms of the specific aspect of the model that is homologous to the human disorder. A wide range of animal models of affective disorders, primarily depression, has been developed to date. They include models in which "depressive behavior" is the result of genetic selection or manipulation, environmental stressors during development or in adulthood, or pharmacologic treatments. The assessment of these animal models is based either on behavioral tests measuring traits that are homologous to symptoms of the human disorder they model, or behavioral tests responsive to appropriate pharmacologic treatments. The goal of this review is to focus on relatively recent developments of selected models, to aid in understanding their strengths and weaknesses, and to help those choosing the difficult task of developing novel animal models of affective disorders. The ideal animal model of affective disorders of the future would be an endogenous, genetic model that reiterates the essential, core aspects of the human disease and responds to the standard regimens of therapy. Because complex diseases have been approached from the genetic startpoint by using rodent models, a genetic model of affective disorder would open up possibilities for genetic analysis of polygenic traits that seem to underlie these disorders.     

Evaluation of animal models of neurobehavioral disorders

Animal models play a central role in all areas of biomedical research. The process of animal model building, development and evaluation has rarely been addressed systematically, despite the long history of using animal models in the investigation of neuropsychiatric disorders and behavioral dysfunctions. An iterative, multi-stage trajectory for developing animal models and assessing their quality is proposed. The process starts with defining the purpose(s) of the model, preferentially based on hypotheses about brain-behavior relationships. Then, the model is developed and tested. The evaluation of the model takes scientific and ethical criteria into consideration. Model development requires a multidisciplinary approach. Preclinical and clinical experts should establish a set of scientific criteria, which a model must meet. The scientific evaluation consists of assessing the replicability/reliability, predictive, construct and external validity/generalizability, and relevance of the model. We emphasize the role of (systematic and extended) replications in the course of the validation process. One may apply a multiple-tiered 'replication battery' to estimate the reliability/replicability, validity, and generalizability of result. Compromised welfare is inherent in many deficiency models in animals. Unfortunately, 'animal welfare' is a vaguely defined concept, making it difficult to establish exact evaluation criteria. Weighing the animal's welfare and considerations as to whether action is indicated to reduce the discomfort must accompany the scientific evaluation at any stage of the model building and evaluation process. Animal model building should be discontinued if the model does not meet the preset scientific criteria, or when animal welfare is severely compromised. The application of the evaluation procedure is exemplified using the rat with neonatal hippocampal lesion as a proposed model of schizophrenia. In a manner congruent to that for improving animal models, guided by the procedure expounded upon in this paper, the developmental and evaluation procedure itself may be improved by careful definition of the purpose(s) of a model and by defining better evaluation criteria, based on the proposed use of the model.     

Validation criteria for animal models of human mental disorders: Learned helplessness as a paradigm case

1. Three sets of criteria are proposed for assessing animal models of human mental disorders: predictive validity (performance in the test predicts performance in the condition being modelled), face validity (phenomenological similarity) and construct validity (theoretical rationale).

2. The problems inherent in each of these validation procedures are discussed, and their application to the learned helplessness model of depression is examined.

3. It is concluded that whilst the model has good predictive validity, important questions about face validity remain unanswered, and construct validity has not yet been established.

4. The distinctions between animal models and some related experimental procedures are also discussed.     

Translational animal models of autism and neurodevelopmental disorders

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.     

Neurotransmitter specific alterations in dementing disorders: Insights from animal models

Recent years have witnessed considerable change in the conceptualization of the pathophysiology of the cognitive impairments in dementing disorders, as a result of synaptic neurochemical analyses. Profound reductions in the forebrain cholinergic projections occur in Alzheimer's disease. In GM₁ gangliosidosis, variable alterations in neurotransmitter related processes that are located in synaptic membranes have been described. Exploitation of animal models of human disorders resulting in dementia may further clarify the dynamic alterations in the biochemical processes required for effective neurotransmission in cortex.     

Cell therapy and stem cells in animal models of motor neuron disorders

Amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (or Kennedy's disease), spinal muscular atrophy and spinal muscular atrophy with respiratory distress 1 are neurodegenerative disorders mainly affecting motor neurons and which currently lack effective therapies. Recent studies in animal models as well as primary and embryonic stem cell models of ALS, utilizing over-expression of mutated forms of Cu/Zn superoxide dismutase 1, have shown that motor neuron degeneration in these models is in part a non cell-autonomous event and that by providing genetically non-compromised supporting cells such as microglia or growth factor-excreting cells, onset can be delayed and survival increased. Using models of acute motor neuron injury it has been shown that embryonic stem cell-derived motor neurons implanted into the spinal cord can innervate muscle targets and improve functional recovery. Thus, a rationale exists for the development of cell therapies in motor neuron diseases aimed at either protecting and/or replacing lost motor neurons, interneurons as well as non-neuronal cells. This review evaluates approaches used in animal models of motor neuron disorders and their therapeutic relevance.     

Applications of positron emission tomography in animal models of neurological and neuropsychiatric disorders

Positron emission tomography (PET) provides dynamic images of the biodistribution of radioactive tracers in the brain. Through application of the principles of compartmental analysis, tracer uptake can be quantified in terms of specific physiological processes such as cerebral blood flow, cerebral metabolic rate, and the availability of receptors in brain. Whereas early PET studies in animal models of brain diseases were hampered by the limited spatial resolution of PET instruments, dedicated small-animal instruments now provide molecular images of rodent brain with resolution approaching 1mm, the theoretic limit of the method. Major applications of PET for brain research have consisted of studies of animal models of neurological disorders, notably Parkinson's disease (PD), Alzheimer's disease (AD), and Huntington's disease (HD), stroke, epilepsy and traumatic brain injury; these studies have particularly benefited from selective neurochemical lesion models (PD), and also transgenic rodent models (AD, HD). Due to their complex and uncertain pathophysiologies, corresponding models of neuropsychiatric disorders have proven more difficult to establish. Historically, there has been an emphasis on PET studies of dopamine transmission, as assessed with a range of tracers targeting dopamine synthesis, plasma membrane transporters, and receptor binding sites. However, notable recent breakthroughs in molecular imaging include the development of greatly improved tracers for subtypes of serotonin, cannabinoid, and metabotropic glutamate receptors, as well as noradrenaline transporters, amyloid-β and neuroinflammatory changes. This article reviews the considerable recent progress in preclinical PET and discusses applications relevant to a number of neurological and neuropsychiatric disorders in humans.     

Chronic implantation of deep brain stimulation leads in animal models of neurological disorders

Deep brain stimulation (DBS) has routinely been used as a treatment option in Parkinson's disease (PD), tremor disorders and, more recently, dystonia. Here, we describe a method of implantation of DBS leads in the monkey model of PD. By adapting procedures used in human patients, we have devised implantation techniques that can be readily applied to any animal model in which stimulation of subcortical structures is desired. The procedure for implantation consists of microelectrode mapping of the target structure, DBS lead preparation and implantation, and verification of lead placement. The stimulation system described in this paper allows for simultaneous recording of neuronal activity (during stimulation) and observation of animal behavior without restriction of the subject's head or body. In addition, we detail techniques for stimulation and recording from distant structures (utilizing either a one or two chamber system) to facilitate examination of the effects of DBS on neural activity. Thus, the correlation of changes in neuronal activity with behavior during stimulation of subcortical structures can be accomplished. In addition, the use of leads in primates which are analogous in size to human devices allows for close reproduction of the effects of stimulation as observed in humans.