Clinical neuroscience research最新文献

{"title":"Pharmacology of autism","authors":"Christopher J. McDougle,&nbsp;Kimberly A. Stigler,&nbsp;Craig A. Erickson,&nbsp;David J. Posey","doi":"10.1016/j.cnr.2006.06.012","DOIUrl":"10.1016/j.cnr.2006.06.012","url":null,"abstract":"<div><p><span>The purpose of this review is to discuss the pharmacology of autistic disorder<span> (autism) and other pervasive developmental disorders (PDDs) from the perspective of specific target symptom domains of behavior. Drug treatment strategies directed toward the following target symptom domains are included: motor hyperactivity and inattention; interfering stereotypical and repetitive behavior; aggression and self-injurious behavior (SIB); and the core social impairment of autism and other PDDs. For motor hyperactivity and inattention, studies have indicated that the α</span></span>₂<span><span><span><span><span> adrenergic agonists<span>, clonidine<span> and guanfacine<span>, are useful. A placebo-controlled study by the Research Units on Pediatric Psychopharmacology (RUPP) Autism Network found </span></span></span></span>methylphenidate to be efficacious in 49% of subjects with various PDDs for these target symptoms. Preliminary data with the </span>norepinephrine reuptake inhibitor </span>atomoxetine<span><span> are encouraging. For interfering stereotypical and repetitive behavior, controlled studies of the selective serotonin reuptake inhibitor </span>fluvoxamine found the drug to be more efficacious and better tolerated in adults than children with autism and other PDDs. A recent controlled study of low-dose liquid </span></span>fluoxetine<span> found the drug more efficacious than placebo for interfering repetitive behavior and well tolerated. A large placebo-controlled study of the atypical antipsychotic risperidone found the drug to be efficacious for reducing aggression, SIB and tantrumming in 70% of children with autism and that the response was maintained for up to 6 months. Open-label studies of other atypical antipsychotics are generally encouraging. A small, single-blind study of the glutamatergic agent </span></span><span>d</span><span>-cycloserine showed significant benefit for the social withdrawal of autism. Future directions include studying coactive pharmacological treatment strategies utilizing more than one drug to target more than one target symptom domain in individuals with autism and other PDDs.</span></p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.06.012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54072577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebellar contributions to autism spectrum disorders","authors":"Greg Allen","doi":"10.1016/j.cnr.2006.06.002","DOIUrl":"10.1016/j.cnr.2006.06.002","url":null,"abstract":"<div><p><span>The pathophysiology of </span>autism<span> appears to encompass a number of different brain structures and systems. However, the most consistent site of neural abnormality in autism is the cerebellum. Postmortem investigations have reported a variety of anomalies, most notably a reduction in the number of Purkinje neurons. Additionally, structural neuroimaging studies have shown volumetric changes in the cerebellum, including decreases in gray matter and increases in white matter. Emerging evidence for cerebellar abnormality in autism was paralleled by a revolution in our understanding of normal cerebellar function and cerebellar connectivity, such that the importance of elucidating the contributions of the cerebellum to autism is now clear. In fact, recent brain-behavior correlation studies suggest that cerebellar abnormality may play a more central role in autism than previously thought. At present, it is crucial that we increase our understanding of cerebellar functioning in autism, and functional neuroimaging studies are just beginning to reveal the possible role(s) of cerebellar dysfunction in this disorder. In this review, evidence for cerebellar anatomic and functional abnormality in autism will be delineated. This will be followed by consideration of the implications of cerebellar abnormality in autism. Two major questions will be addressed: (1) how might dysfunction of the cerebellum impact the development of connectivity between the cerebellum and other brain systems, and (2) how might cerebellar dysfunction impact behavior and the symptoms of autism. The paper concludes with a discussion of how cerebellar abnormalities might inform our understanding of the etiology of autism spectrum disorders.</span></p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.06.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54071937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of autism: Current controversies and research directions","authors":"Judith K. Grether","doi":"10.1016/j.cnr.2006.06.009","DOIUrl":"10.1016/j.cnr.2006.06.009","url":null,"abstract":"<div><p><span>In many respects, the epidemiology of </span>autism is still in its infancy. Although important questions remain unanswered, epidemiologists are making significant progress in several areas of inquiry that will be addressed in this presentation: How common is autism? Has the prevalence changed over time? What demographic and environmental risk factors have been identified that may provide clues to underlying etiology? What research is being done to search for early biologic markers for autism and related disorders? Epidemiologists like to count “cases” to estimate the frequency with which autism occurs in a population. However, prevalence estimates are heavily influenced by the methodology used for identification of affected individuals, making it difficult to compare prevalence across different time periods or populations. Current estimates of autism prevalence based on different methodologies and factors contributing to observed time trends will be provided for consideration. The tools of epidemiology are also useful for identifying demographic and environmental risk factors that may provide clues to underlying etiology. Preliminary data will be presented from large California studies on characteristics of parents and newborns that are associated with risk of autism. Finally, in collaboration with basic scientists, slow progress is being made in identifying and evaluating early biologic markers for autism. Current studies will be described and preliminary data on newborns presented.</p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.06.009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54072412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormalities of cortical minicolumnar organization in the prefrontal lobes of autistic patients","authors":"M.F. Casanova ,&nbsp;I. van Kooten ,&nbsp;A.E. Switala ,&nbsp;H. van Engeland ,&nbsp;H. Heinsen ,&nbsp;H.W.M. Steinbusch ,&nbsp;P.R. Hof ,&nbsp;C. Schmitz","doi":"10.1016/j.cnr.2006.06.003","DOIUrl":"10.1016/j.cnr.2006.06.003","url":null,"abstract":"<div><p><span><span>Recent functional imaging studies suggest deficits in connectivity between disparate and distant regions in the brains of autistic individuals. One possible explanation to these findings is the presence of modular abnormalities in the neocortex of autistic patients: a change in neuronal specialization within minicolumns that emphasizes short connecting fibers. In this study, we expand on previous findings by exploring the topography of minicolumnar abnormalities in autism. Our postmortem study included six patients with autism (DSM-IV-TR and ADI-R diagnosed) and six age-matched controls. Entire brain hemispheres were </span>celloidin embedded, serially sectioned, and stained with gallocyanin. Digital photomicrographs of </span><em>n</em> <!-->=<!--> <span>9 cortical areas (including paralimbic, heteromodal association, unimodal association, and primary areas) obtained at high magnification were assembled into montages covering the entire cortical thickness. Stained cell somata were segmented from neuropil by thresholding. Computer image analysis clustered neurons into minicolumnar fragments. The full width of the image region nearest each fragment and the width of the cell-dense core of the fragment were estimated. The difference between these two quantities can be used as a measure of the peripheral neuropil space of minicolumns. We found an interaction of diagnosis and region for peripheral neuropil space (</span><em>p</em> <!-->=<!--> <span>0.041). Post hoc analysis revealed significant differences (</span><em>p</em> <!-->&lt;<!--> <span>0.05) for the frontopolar region (area 10) and the anterior cingulate gyrus (area 24). The frontopolar cortex is involved in executive functions by implementing control over internally generated thoughts and relational integration (combination of multiple cognitive rules). The anterior cingulate gyrus is involved in the analysis of socially salient information, including the processing of familiar faces. Pathological findings in these areas may provide a correlate to some of the more salient manifestations of autism.</span></p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54071991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early diagnosis of children with autism spectrum disorders","authors":"Catherine Lord,&nbsp;Rhiannon Luyster","doi":"10.1016/j.cnr.2006.06.005","DOIUrl":"10.1016/j.cnr.2006.06.005","url":null,"abstract":"<div><p>Research focusing on early development in children with Autism Spectrum Disorders (ASD) has been of particular interest in recent years. A greater understanding of the accuracy of early diagnosis, as well as the developmental pathways that are observed in young children with ASD, is of both theoretical and practical importance. In accordance with these concerns, this review addresses questions about three topics: the reliability of early diagnosis, the validity of using narrow versus broad diagnostic categories, and trajectories of development in children with ASD. Findings from two prospective longitudinal studies are reviewed. The first investigation included children referred for ASD at age 2 who were followed for one year. The second study followed children referred for ASD at age 2 until age 9. Results suggested that early diagnoses can be made reliably, that there is no empirical evidence for using narrowly defined diagnostic categories within ASD and that trajectories of development showed considerable heterogeneity.</p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.06.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54072197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"OBC (CONTENTS)","authors":"","doi":"10.1016/S1566-2772(06)00059-4","DOIUrl":"10.1016/S1566-2772(06)00059-4","url":null,"abstract":"","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1566-2772(06)00059-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56847066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fetal alcohol syndrome, fetal alcohol exposure and neuro–endocrine–immune interactions","authors":"Anna N. Taylor ,&nbsp;Francesco Chiappelli ,&nbsp;Susan H. Tritt ,&nbsp;Raz Yirmiya ,&nbsp;Horacio E. Romeo","doi":"10.1016/j.cnr.2006.05.001","DOIUrl":"10.1016/j.cnr.2006.05.001","url":null,"abstract":"<div><p><span><span>Human and animals studies have established that fetal alcohol exposure (FAE) is associated with significant impairments in cellular immune functions and marked disturbances in the interactions between the nervous, endocrine and immune systems. These observations have important clinical implications suggesting that FAE may lead to profound impairments in those aspects of the immune response that are most crucial for initiating, regulating, and sustaining immune surveillance against minor as well as lethal infectious agents, and against malignancies. FAE is a prenatal intervention, with effects on maternal and fetal </span>glucocorticoids<span><span> and long-term effects on neuro–endocrine–immune outcomes The marked effects of FAE upon neuro-endocrine–immune function that mediate many of the host's defense responses to infections in animal models are the subject of this review. Specifically FAE attenuates central nervous system (CNS)-mediated responses to immune challenges such as </span>lipopolysaccharide (LPS) and interleukin (IL)-1-beta, including sympathetic outflow to the spleen, thermoregulatory and neuroendocrine processes and sickness behavior. Ethanol may have significant effects on the fetus either by a direct toxic effect during </span></span>critical periods of development or because of the stress response it induces in the pregnant female. Maternal adrenalectomy in Sprague–Dawley rats or genetic impairment of hypothalamic–pituitary–adrenal (HPA) function, as in Lewis rats, were found to reverse the effects of prenatal ethanol on neuro–endocrine–immune responses in the offspring. These experimental studies suggest that activation of the maternal HPA axis may play a role in the developmental and long-term effects of ethanol.</p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.05.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54071734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innervation of lymphoid organs: Clinical implications","authors":"Denise L. Bellinger ,&nbsp;Brooke A. Millar ,&nbsp;Sam Perez ,&nbsp;Jeff Carter ,&nbsp;Carlo Wood ,&nbsp;Srinivasan ThyagaRajan ,&nbsp;Christine Molinaro ,&nbsp;Cheri Lubahn ,&nbsp;Dianne Lorton","doi":"10.1016/j.cnr.2006.04.003","DOIUrl":"10.1016/j.cnr.2006.04.003","url":null,"abstract":"<div><p><span><span>Host defense against pathogens is regulated by cross-talk between two major adaptive systems of the body—the nervous and immune systems. This bidirectional communication is essential for maintaining homeostasis. Sympathetic nerves that innervate lymphoid tissues provide one of the major outflows from the brain to regulate tissue repair and host defense. This review focuses on the role of (sympathetic nervous system) SNS in neuroimmune regulation, an area that has received much less attention than the other major immunoregulatory pathway, the hypothalamo–pituitary–adrenal (HPA) axis. Research over the past 25 years has demonstrated that </span>norepinephrine<span> (NE) fulfills the criteria for neurotransmission<span><span> in lymphoid tissue, with both primary and secondary immune organs receiving an extensive supply of sympathetic nerves that directly contact with immunocytes. Under stimulation, NE released from terminals in secondary lymphoid organs interacts with </span>adrenergic receptors (AR) expressed on immune cells to affect the development, trafficking, circulation, proliferation, </span></span></span>cytokine production, and the functional activity of variety of lymphoid and myeloid cells. Our knowledge of the role of sympathetic nerves in modulating hematopoietic functions of primary lymphoid organs (bone marrow and thymus) and mucosal immunity are extremely limited. While the immune system is not absolutely dependent upon signals from the brain to function, sympathetic-immune modulation may drive host defense toward protection against, or progression toward, immune-related diseases. Additionally, signals from the (SNS) may enhance immune readiness during disease- or injury-induced ‘fight-or-flight’ responses. A better understanding of neural–immune interactions may foster the development of strategies for treating immune-mediated diseases, particularly where neuroimmune cross-talk may be dysregulated.</p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.04.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54071408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motoneurons and CD4+ effector T cell subsets: Neuroprotection and repair","authors":"Susanna C. Byram ,&nbsp;Craig J. Serpe ,&nbsp;Cynthia A. DeBoy ,&nbsp;Virginia M. Sanders ,&nbsp;Kathryn J. Jones","doi":"10.1016/j.cnr.2006.06.001","DOIUrl":"10.1016/j.cnr.2006.06.001","url":null,"abstract":"<div><p><span><span>Both neuroprotective and neurodestructive effects of the immune system have been described, although the regulatory nature of such contradictory actions have yet to be determined. We combined the </span>facial nerve injury with immunodeficient mouse models and our findings provide the foundation for a working model of CD4</span>⁺<span>T cell-mediated motoneuron survival and axonal regeneration after injury. Key to this model is the new concept that CD4</span>⁺<span><span> effector T cell subsets play distinctive roles in motoneuron reparative processes, with the </span>Th2 cell<span> mediating FMN survival and the Th1 cell<span> mediating functional recovery. This concept places the motoneuron as the central regulator of the immune response that occurs after direct axonal trauma. The postulated Th2/Th1 paradigm creates a balance essential to the health of the motoneuron and to its ability to mount a graded response to injury that is geared toward survival and structural/functional recovery for the organism, respectively. Understanding the inherent capabilities of the CNS to direct the local immune reaction to injury is essential to elucidation of the pathophysiology<span> inherent in neurodegenerative diseases<span>, particularly ALS and other motoneuron disorders, in which compromised neurons may lose the ability to regulate a local immune response, such that an imbalance occurs and results in a pro-inflammatory, neurodestructive environment. In the case of motoneuron disease, such as ALS, we hypothesize that the diseased motoneuron cannot direct a neuroprotective immune response, resulting in a destructive pro-inflammatory environment near the diseased motoneuron.</span></span></span></span></span></p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54071899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimmunotoxicology: Modulation of neuroimmune networks by toxicants","authors":"N.G. Pabello,&nbsp;D.A. Lawrence","doi":"10.1016/j.cnr.2006.04.004","DOIUrl":"10.1016/j.cnr.2006.04.004","url":null,"abstract":"<div><p>For the past few decades, neuroimmunology research has delineated pathways and mechanisms on the reciprocal interactions that exist between the nervous and immune systems. While there also has been a substantial amount of data on the effects of toxicants on the immune system (immunotoxicity) and the nervous system (neurotoxicity), the effects of toxicants on the dysregulation of one organ system leading to malfunctions of another, present a major concern for health. Building on substantiated neuroimmunological research, the multidisciplinary field of neuroimmunotoxicology has emerged. This review briefly describes some presently known links between the nervous and immune systems, namely the hypothalamic–pituitary–adrenal (HPA) axis and the autonomic (sympathetic and parasympathetic) nervous system, followed by a discussion of some mechanisms by which exposure to the prototypic toxicants, lead, mercury, and PCB's, may directly or indirectly modulate neuroimmune networks. Additionally, the possible sequelae of such exposures have been highlighted in relation to the etiology or progression of diseases and treatments.</p></div>","PeriodicalId":87465,"journal":{"name":"Clinical neuroscience research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2006-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cnr.2006.04.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54072099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}