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71.
Background: The Profile of Pragmatic Impairment in Communication (PPIC) is a clinical rating scale designed for the assessment of multiple facets of pragmatic language impairment in neuropsychiatric disorders. The PPIC has its origin in Grice's analysis of implicature and the Gricean principle of co‐operation and conversational maxims. Aims: We sought to evaluate the psychometric properties of the PPIC and to generate a profile of pragmatic language impairment associated with Alzheimer's disease (AD). Methods & Procedures: Speech samples were solicited from patients with AD (n = 13) and age‐matched healthy volunteers (n = 13) using several structured/semi‐structured tasks. Three trained raters made blind ratings on the PPIC on two occasions. Other raters evaluated mental status, aphasia, and communicative effectiveness. A generalisability analysis was conducted. Outcomes & Results: Good to excellent generalisability coefficients (0.86–0.94) were observed on most PPIC scales. PPIC ratings were strongly related to mental status and communicative effectiveness but not associated with aphasia. Diagnosis of AD made no substantive contribution to the prediction of PPIC ratings independently of mental status impairment. Conclusions: Results demonstrate evidence of good to excellent reliability, convergent validity, and discriminant validity of most PPIC scales. The observed associations are consistent with the view that pragmatic language impairment in AD is primarily a function of cognitive decline. 相似文献
72.
Diefenbach Gretchen J. Stevens Kimberly T. Dunlap Amanda Nicholson Alycia M. Grella Olivia N. Pearlson Godfrey Assaf Michal 《Journal of autism and developmental disorders》2022,52(4):1435-1443
Journal of Autism and Developmental Disorders - Cognitive reappraisal is associated with reduced emotional distress; however, little is known about the nature of this relationship in autism. This... 相似文献
73.
C. Vogel C. Parsons K. Godfrey S. Robinson N. C. Harvey H. Inskip C. Cooper J. Baird 《Osteoporosis international》2016,27(3):1011-1019
Summary
A healthy diet positively influences childhood bone health, but how the food environment relates to bone development is unknown. Greater neighbourhood access to fast-food outlets was associated with lower bone mass among infants, while greater access to healthy speciality stores was associated with higher bone mass at 4 years.Introduction
Identifying factors that contribute to optimal childhood bone development could help pinpoint strategies to improve long-term bone health. A healthy diet positively influences bone health from before birth and during childhood. This study addressed a gap in the literature by examining the relationship between residential neighbourhood food environment and bone mass in infants and children.Methods
One thousand one hundred and seven children participating in the Southampton Women’s Survey, UK, underwent measurement of bone mineral density (BMD) and bone mineral content (BMC) at birth and 4 and/or 6 years by dual-energy X-ray absorptiometry (DXA). Cross-sectional observational data describing food outlets within the boundary of each participant’s neighbourhood were used to derive three measures of the food environment: the counts of fast-food outlets, healthy speciality stores and supermarkets.Results
Neighbourhood exposure to fast-food outlets was associated with lower BMD in infancy (β?=??0.23 (z-score): 95 % CI ?0.38, ?0.08) and lower BMC after adjustment for bone area and confounding variables (β?=??0.17 (z-score): 95 % CI ?0.32, ?0.02). Increasing neighbourhood exposure to healthy speciality stores was associated with higher BMD at 4 and 6 years (β?=?0.16(z-score): 95 % CI 0.00, 0.32 and β?=?0.13(z-score): 95 % CI ?0.01, 0.26 respectively). The relationship with BMC after adjustment for bone area and confounding variables was statistically significant at 4 years, but not at 6 years.Conclusions
The neighbourhood food environment that pregnant mothers and young children are exposed may affect bone development during early childhood. If confirmed in future studies, action to reduce access to fast-food outlets could have benefits for childhood development and long-term bone health.74.
75.
Relapsing polychondritis (RP) is a rare disease characterized by recurrent inflammation of cartilaginous and other proteoglycan-rich tissues. Respiratory tract involvement is a common cause of morbidity and mortality in RP. We describe a patient whose clinical features at onset of disease were typical of asthma. Later, the patient developed symptoms and signs characteristic of RP. Tracheobronchomalacia necessitated airway support by stenting. The possibility that airway obstruction in the initial stages of RP is due to airway inflammation and that early, aggressive immunosuppressive treatment of RP may delay or prevent irreversible cartilaginous destruction and airway collapse are discussed. 相似文献
76.
Childhood Bone Mineral Content Is Associated With Methylation Status of the RXRA Promoter at Birth 下载免费PDF全文
Keith M Godfrey Cameron McLean Emma Garratt Georgia Ntani Lucy Davies Robert Murray Hazel M Inskip Peter D Gluckman Mark A Hanson Cyrus Cooper 《Journal of bone and mineral research》2014,29(3):600-607
Maternal vitamin D deficiency has been associated with reduced offspring bone mineral accrual. Retinoid‐X receptor‐alpha (RXRA) is an essential cofactor in the action of 1,25‐dihydroxyvitamin D (1,25[OH]2‐vitamin D), and RXRA methylation in umbilical cord DNA has been associated with later offspring adiposity. We tested the hypothesis that RXRA methylation in umbilical cord DNA collected at birth is associated with offspring skeletal development, assessed by dual‐energy X‐ray absorptiometry, in a population‐based mother‐offspring cohort (Southampton Women's Survey). Relationships between maternal plasma 25‐hydroxyvitamin D (25[OH]‐vitamin D) concentrations and cord RXRA methylation were also investigated. In 230 children aged 4 years, a higher percent methylation at four of six RXRA CpG sites measured was correlated with lower offspring bone mineral content (BMC) corrected for body size (β = ?2.1 to ?3.4 g/SD, p = 0.002 to 0.047). In a second independent cohort (n = 64), similar negative associations at two of these CpG sites, but positive associations at the two remaining sites, were observed; however, none of the relationships in this replication cohort achieved statistical significance. The maternal free 25(OH)‐vitamin D index was negatively associated with methylation at one of these RXRA CpG sites (β = ?3.3 SD/unit, p = 0.03). Thus, perinatal epigenetic marking at the RXRA promoter region in umbilical cord was inversely associated with offspring size–corrected BMC in childhood. The potential mechanistic and functional significance of this finding remains a subject for further investigation. © 2014 American Society for Bone and Mineral Research. 相似文献
77.
Leah H. Rubin C. Sue Carter Jeffrey R. Bishop Hossein Pournajafi-Nazarloo Lauren L. Drogos S. Kristian Hill Anthony C. Ruocco Sarah K. Keedy James L. Reilly Matcheri S. Keshavan Godfrey D. Pearlson Carol A. Tamminga Elliot S. Gershon John A. Sweeney 《Schizophrenia bulletin》2014,40(6):1374-1384
Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h
2 = 0.79, P = 3.97e−15) and AVP (h
2 = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.Key words: oxytocin, vasopressin, schizophrenia, bipolar disorder, emotion recognition 相似文献
78.
The Diagnostic and Statistical Manual of Mental Disorders (DSM) has provided diagnostic reliability across observers while neglecting biological validity. The current theme issue explores the boundaries between schizophrenia and bipolar disorder, using neuro-cognition, systems neuroscience, and genetics as points of departure to begin consideration of a biologically based reclassification of these illnesses.Key words: schizophrenia, bipolar, validity, classification
“Ce n’est qu’un début, continuons le débat.” (“This is just the beginning, let’s continue the debate.”)French students (May 1968)In the ongoing debate over where to draw the boundary (if any) between schizophrenia and bipolar disorder, the arguments are familiar, the battle lines clearly drawn, but the scientific observations continue to be updated in important ways that make a reassessment timely. The current issue of the Bulletin features comprehensive overviews from the vantage points of genetics and systems neuroscience that continue to reshape the nature of the debate.Arguments over the discrete vs continuous nature of schizophrenia and bipolar disorder are important because they promise to translate into improved, more patient-specific prognoses and therapies.Disease classifications proceed from some logical beginning: In the absence of both informative biological data and clinical physical signs, clinical phenomenology, family history, and disease course constitute the mandatory starting points on the road to meaningful diagnostic categories. Hence, Kraepelin began in 1893 by defining these 2 entities based on longitudinal course and outcome. He had already begun to backtrack from this dichotomy by 1920 in the final edition of his Lehrbuch.1 Before that, the follow-up studies from his pupil Zendig2 demonstrated favorable outcome in a third of Kraepelin’s own large schizophrenia case series. The boundaries between clinical entities defined by phenomenology appear to be distributed on a continuum and to lack sharp demarcations. Thus, one-third of patients with schizophrenia simultaneously meet criteria for major depression,3 one-third of patients with bipolar illness manifest psychotic symptoms, which in some cases persist between overt episodes of mood disturbance.4 Recently, Keshavan5 showed no point of symptomatic rarity between schizophrenia, psychotic bipolar disorder, and schizoaffective disorder in the large Bipolar Schizophrenia Network on Intermediate Phenotypes sample. Similarly, the Suffolk County mental health project showed a lack of boundary, defined in terms of functioning, between schizoaffective disorder and schizophrenia,6 although there are occasional reports of biological distinctions between them, for example.7 Response to medications has not been especially helpful as a guide. The early Northwick Park studies offered some suggestion that patients with psychosis responded to antipsychotics, patients with mood disorders responded to lithium, and patients with features of both syndromes responded to both medicines.8 However, antipsychotic medications are now prescribed routinely for schizophrenia, bipolar disorder, and antidepressant treatment–resistant major depression, presumably, in part because they are effective in these conditions. Real-world experience with these patients shows that many are being prescribed polypharmaceutical cocktails of antipsychotic, antidepressant, and mood stabilizer medications. As is frequently pointed out, the one exception to this cross-diagnostic promiscuity seems to be lithium, to which about one-third of nonpsychotic bipolar patients and a much smaller proportion of classic schizophrenia patients respond with symptom remission.9 Although both schizophrenia and bipolar disorder are clearly heritable, as Cardno and Owen10 illustrate in this issue, segregation within families is less clear-cut than believed previously, and these conditions do not decisively “breed true,”11 although psychotic bipolar illness may aggregate familially.4 Genome wide–association studies tend to uncover candidate single-nucleotide polymorphisms that confer risk for both disorders, and genes such as DISC-1 are also associated with increased risk for schizophrenia, bipolar illness, major depression, and other conditions.As pointed out by Frangou12 in this issue, emergent properties such as cognition are an excellent starting point for examining differences between syndromes because they are reliably assessed across centers with standardized tests. Because they demonstrate both heritability and frequent abnormality in unaffected first-degree relatives, they constitute phenotypes, conceptually.11 In this issue, Reilly and Sweeney13 point out, “Considerable evidence supports the notion that broadly impaired cognitive functioning is central to the pathophysiology of psychosis, and … [its] magnitude, rather than [its] presence differentiates syndromes within the psychosis spectrum.” They further suggest, “The detection of specific effects … is challenging yet critical if the field is to further advance development of pharmacological treatments targeting cognitive deficits … .” In our search for specificity, we ask if there is any point in the illness course where differences emerge? Frangou12 notes that important differences are detectable in that premorbid cognitive and social abnormalities appear to be less marked in bipolar illness, although these differences diminish after illness onset. Similarly, copy number variants occurring in central nervous system–relevant genes are significantly commoner in schizophrenia than bipolar disorder, although, as mentioned earlier, genetic differences are not schizophrenia-specific, being found in association with other serious neurodevelopmental disorders, including epilepsy, learning disabilities, and autism spectrum disorders.Where do we go from here? This debate will continue until distinct etiopathologies for schizophrenia and bipolar disorder emerge—parallel events that ultimately ended this type of debate in clinical medicine. Ultimately, though, we are likely to define the new “illnesses” based on regularly co-occurring biological (including genetic) characteristics. One possibility in the short term is that we remain diagnostically uncommitted and code psychosis and mood disorder separately, as suggested by Kotov.14 Some researchers have argued strongly against this stance.15 Different associations with indices of neurodevelopmental impairment may be one point of departure as suggested in this issue by Cardno and Owen10 and Frangou.12 Frangou suggests that “abnormalities in multiple large-scale neural networks and alterations in local micro-scale circuitry within associative and sensory cortices” caused by environmental insults and genetic variation, “disrupt processes responsible for orderly neuronal configuration” (eg, synaptic integrity, neurotransmission). Identifying such abnormalities then proceeds logically toward a redefinition of major mental illnesses based on systems neuroscience and the defining of “more homogeneous groups of patients.”12 This strategy may reveal similarities across all putatively developmentally based psychiatric illnesses, including autism and learning disabilities, extending beyond schizophrenia and bipolar disorder. Cardno and Owen10 suggest we move away from lifetime diagnostic categories toward a system that relies more on “categorical or dimensional syndromes, networks of correlated symptoms, and/or endophenotypes … according to particular research or clinical requirements.”Regarding the genetic underpinnings of these disorders, we ask, “Precisely what is being inherited?” One possibility is that a small number of genes are being passed on that are responsible for multiple clinical manifestations, from mood instability to psychoticism (ie, an instance of pleiotropy). Another possibility is that risk is being inherited for more than one behavioral trait, which happens to commonly co-occur, for a variety of reasons including assortative mating. For example, “psychoticism,” whose pure form is expressed as Kraepelinian schizophrenia, and “mood instability,” whose pure form is expressed as nonpsychotic bipolar illness, may both be passed on, with the possibility of them being mixed together in various combinations to produce, eg, schizoaffective or psychotic bipolar disorder.What might the new disease landscape look like, whether based on neuronal circuit-based endophenotypes or commonalities in risk genes and their associated molecular biological processes? One possibility is that several clinical groupings will emerge that are phenomenologically heterogeneous, containing examples of what we now define clinically as schizophrenia and bipolar disorder, but consistent in their underlying biological markers. This would be analogous to the fate of “dropsy” in medicine. A less satisfactory outcome would be that more knowledge of etiopathology would result in the fissuring of familiar clinical syndromes into unique biological clusters, representing agglomerations defined by differing pathologic processes leading to disruption in final common biological pathways, more along the lines of the manner in which Alzheimer’s disease is now considered. The ultimate hope is to aggregate disorders according to biological mechanisms that underlie clinical phenomena and that point us toward evidence-based treatment targets and interventions. This is consistent with the National Institute of Mental Health’s Research Domain Criteria16 and the earlier cognitive neuropsychiatric approach.17–19 This debate began with Kraepelin, is moving forward, but continues. 相似文献
79.
80.
Malnic B Godfrey PA Buck LB 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(8):2584-2589
Humans perceive an immense variety of chemicals as having distinct odors. Odor perception initiates in the nose, where odorants are detected by a large family of olfactory receptors (ORs). ORs have diverse protein sequences but can be assigned to subfamilies on the basis of sequence relationships. Members of the same subfamily have related sequences and are likely to recognize structurally related odorants. To gain insight into the mechanisms underlying odor perception, we analyzed the human OR gene family. By searching the human genome database, we identified 339 intact OR genes and 297 OR pseudogenes. Determination of their genomic locations showed that OR genes are unevenly distributed among 51 different loci on 21 human chromosomes. Sequence comparisons showed that the human OR family is composed of 172 subfamilies. Types of odorant structures that may be recognized by some subfamilies were predicted by identifying subfamilies that contain ORs with known odor ligands or human homologs of such ORs. Analysis of the chromosomal locations of members of each OR subfamily revealed that most subfamilies are encoded by a single chromosomal locus. Moreover, many loci encode only one or a few subfamilies, suggesting that different parts of the genome may, to some extent, be involved in the detection of different types of odorant structural motifs. 相似文献