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81.
Eivind Ystrom Ted Reichborn-Kjennerud Michael C. Neale Kenneth S. Kendler 《Behavior genetics》2014,44(1):1-13
The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies. 相似文献
82.
Elise B. Robinson Kaitlin E. Samocha Jack A. Kosmicki Lauren McGrath Benjamin M. Neale Roy H. Perlis Mark J. Daly 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(42):15161-15165
Autism spectrum disorders (ASDs) are a highly heterogeneous group of conditions—phenotypically and genetically—although the link between phenotypic variation and differences in genetic architecture is unclear. This study aimed to determine whether differences in cognitive impairment and symptom severity reflect variation in the degree to which ASD cases reflect de novo or familial influences. Using data from more than 2,000 simplex cases of ASD, we examined the relationship between intelligence quotient (IQ), behavior and language assessments, and rate of de novo loss of function (LOF) mutations and family history of broadly defined psychiatric disease (depressive disorders, bipolar disorder, and schizophrenia; history of psychiatric hospitalization). Proband IQ was negatively associated with de novo LOF rate (P = 0.03) and positively associated with family history of psychiatric disease (P = 0.003). Female cases had a higher frequency of sporadic genetic events across the severity distribution (P = 0.01). High rates of LOF mutation and low frequencies of family history of psychiatric illness were seen in individuals who were unable to complete a traditional IQ test, a group with the greatest degree of language and behavioral impairment. These analyses provide strong evidence that familial risk for neuropsychiatric disease becomes more relevant to ASD etiology as cases become higher functioning. The findings of this study reinforce that there are many routes to the diagnostic category of autism and could lead to genetic studies with more specific insights into individual cases.The set of conditions diagnosed as autism spectrum disorders (ASDs) vary enormously in their presentation (1). The most severely impaired individuals—often those with intellectual disabilities, limited speech, and severe behavioral problems—can require lifelong care. At the other end of the functional spectrum, people diagnosed with ASDs can be verbally fluent and academically gifted and can achieve independence in adulthood (2, 3). The broad range of cognitive and behavioral profiles seen in diagnosed ASDs has been long viewed as a challenge by the research community (4). Although it is well established that (i) the cognitive/behavioral profile of people diagnosed with ASDs varies widely and (ii) the set of genetic factors related to ASDs varies widely (5, 6), the degree to which phenotype can be used to predict patterns in disease architecture remains unclear.Recent insights into the genetic influences on ASDs offer an opportunity to investigate this question through the lens of de novo vs. familial effects. On average, ASDs run in families. The siblings of children with ASDs are 10–20 times more likely to receive a diagnosis of ASD themselves (7, 8); the parents of children with ASDs are more likely to manifest autistic features, as well as a variety of other neuropsychiatric conditions, such as schizophrenia and bipolar disorder (9, 10). These epidemiologic observations are consistent with analyses suggesting that ASDs are influenced by thousands of common genetic variants transmitted between generations. It has been estimated that common, genotyped SNPs account for 20–60% of variation in ASD risk, although the effect of any individual SNP is likely very small (11–13). Many of these influences are shared with other psychiatric disorders (12, 14), which at least in part explains the familial clustering of different types of behavior problems.However, statistics about ASD heritability reflect an average. For example, there are likely many affected families for whom sibling recurrence risk is less than 10–20%. The strongest evidence toward this claim comes from studies of rare, severely deleterious genetic events that are associated with ASDs (15–20). Events of this type, for example copy number variants and loss of function (LOF) mutations, are often de novo (not seen in an affected individual’s parents). Although cases of ASDs involving a de novo mutation could reflect a concert of spontaneous and inherited genetic events, de novo events of large effect may reduce the likelihood of seeing psychiatric problems in an affected individual’s family members. 相似文献
83.
Diane Mullins Eileen Daly Andrew Simmons Felix Beacher Catherine ML Foy Simon Lovestone Brian Hallahan Kieran C Murphy Declan G Murphy 《Journal of Neurodevelopmental Disorders》2013,5(1):19
Background
Down’s syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer’s disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case–control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population.Method
Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts).Results
AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD.Conclusions
DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less ‘cognitive reserve’. 相似文献84.
PS Spencer K Vandemaele M Richer VS Palmer S Chungong M Anker Y Ayana ML Opoka BN Klaucke A Quarello JK Tumwine 《African health sciences》2013,13(2):183-204
Background
Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.Objective
To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.Methods
Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.Results
Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.Conclusion
Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food. 相似文献85.
该文旨在介绍Beth Israel医疗中心采用大剂量术中放疗(HDR-IORT)治疗复发头颈癌的经验。对2001-2010年间头颈癌局部复发接受大剂量HDR-IORT的患者进行回顾分析。结果,76例患者的87个部位在肿瘤切除后接受了治疗。术后2年控制率为62%。平均总生存期为19个月,其中42%的患 相似文献
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88.
Kurt Kroenke Samantha Outcalt Erin Krebs Matthew J. Bair Jingwei Wu Neale Chumbler Zhangsheng Yu 《General hospital psychiatry》2013
Objective
Anxiety and chronic pain are prevalent and frequently co-occur. Our purpose was to examine the association between anxiety, health-related quality of life (HRQL) and functional impairment in primary care patients with chronic musculoskeletal pain.Methods
Data were drawn from baseline interviews of the 250 primary care patients enrolled in the Stepped Care to Optimize Pain care Effectiveness trial. Validated measures were used to determine the proportion of patients screening positive for five common anxiety disorders: generalized anxiety, panic, social anxiety, posttraumatic stress and obsessive–compulsive disorder. Bivariate analyses examined associations between the type and number of anxiety disorders for which patients screened positive and representative pain, psychological and other HRQL outcomes. Multivariable models controlling for major depression and other covariates examined the association between the number of screen-positive anxiety conditions and functional impairment in psychological [SF-12 mental component summary (MCS) score], pain [Brief Pain Inventory (BPI) interference score] and work (disability days) domains.Results
One hundred fourteen (45%) patients screened positive for at least one anxiety disorder and, compared to the 136 screen-negative patients, had significantly worse scores across multiple pain, psychological and other HRQL domains. Substantial impairment was seen for each of the five screen-positive anxiety conditions and progressively worsened as the number of conditions increased from one (n= 54) to two (n= 26) to ≥ 3 (n= 34). The number of screen-positive anxiety conditions was strongly associated (P< .0001) with worse BPI interference and MCS scores and more disability days in models adjusting for age, sex and medical comorbidity. After further adjusting for major depression, associations were attenuated but remained significant for BPI interference (P< .0001) and MCS (P= .018) and marginally significant for disability days (P= .062).Conclusion
Nearly half of primary care patients with chronic pain screen positive for one or more anxiety disorders, which in turn are adversely associated with impairment across multiple domains of HRQL. Detecting and treating anxiety may be an important component of pain management. 相似文献89.
Variation in Networks and Forms of Support for Care‐Seeking Across the HIV Care Continuum in the Rural Southeastern United States
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Purpose
In spite of progress in understanding the importance of social support for health outcomes in Persons Living with HIV (PLWH), more remains to be known about mechanisms of support most beneficial at each stage of HIV treatment. In this study, we use a qualitative analytic approach to investigate the forms and sources of social support deemed most integral to the diagnosis, care engagement, and medication adherence behaviors of a diverse sample of PLWH in a mostly rural health district in the Southeastern United States.Methods
In‐depth interviews (N = 18) were collected during the qualitative phase of a larger mixed methods needs assessment for the Northeast Georgia Health District. A deductive‐inductive analysis of participant narratives revealed variation in the perceived importance of particular forms and sources of social support during the initial versus advanced stages of HIV care.Findings
PLWH identified the emotional, informational, and appraisal support provided by family as especially critical for emotional stability, coping, and care linkage during the initial stages of diagnosis and treatment. However, once in care, PLWH emphasized informational and instrumental forms of support from care providers and appraisal support from peers as key influences in care engagement and retention behaviors.Conclusion
Increased understanding of the social support mechanisms that contribute to the HIV treatment behaviors of PLWH can fill knowledge gaps in research and inform the efforts of health care providers seeking to leverage various aspects of the social support toward improving the care retention, health, and wellness outcomes of PLWH. 相似文献90.