pinecone/core-2020-05-10-deduplication huggingface dataset:
Rare copy number variants: a point of rarity in genetic risk for bipolar disorder and schizophrenia.

Context  Recent studies suggest that copy number variation in the human genome is extensive and may play an important role in susceptibility to disease, including neuropsychiatric disorders such as schizophrenia and autism. The possible involvement of copy number variants (CNVs) in bipolar disorder has received little attention to date.\ud
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Objectives  To determine whether large (>100 000 base pairs) and rare (found in <1% of the population) CNVs are associated with susceptibility to bipolar disorder and to compare with findings in schizophrenia.\ud
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Design  A genome-wide survey of large, rare CNVs in a case-control sample using a high-density microarray.\ud
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Setting  The Wellcome Trust Case Control Consortium.\ud
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Participants  There were 1697 cases of bipolar disorder and 2806 nonpsychiatric controls. All participants were white UK residents.\ud
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Main Outcome Measures  Overall load of CNVs and presence of rare CNVs.\ud
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Results  The burden of CNVs in bipolar disorder was not increased compared with controls and was significantly less than in schizophrenia cases. The CNVs previously implicated in the etiology of schizophrenia were not more common in cases with bipolar disorder.\ud
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Conclusions  Schizophrenia and bipolar disorder differ with respect to CNV burden in general and association with specific CNVs in particular. Our data are consistent with the possibility that possession of large, rare deletions may modify the phenotype in those at risk of psychosis: those possessing such events are more likely to be diagnosed as having schizophrenia, and those without them are more likely to be diagnosed as having bipolar disorder.Peer-reviewedPublisher Versio
Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease.

PublishedComparative StudyMulticenter StudyResearch Support, Non-U.S. Gov'tCONTEXT: Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD). OBJECTIVE: To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach. DESIGN: Discovery-phase proteomics to identify plasma proteins associated with correlates of AD pathology. Confirmation and validation using immunodetection in a replication set and an animal model. SETTING: A multicenter European study (AddNeuroMed) and the Baltimore Longitudinal Study of Aging. PARTICIPANTS: Patients with AD, subjects with mild cognitive impairment, and healthy controls with standardized clinical assessments and structural neuroimaging. MAIN OUTCOME MEASURES: Association of plasma proteins with brain atrophy, disease severity, and rate of clinical progression. Extension studies in humans and transgenic mice tested the association between plasma proteins and brain amyloid. RESULTS: Clusterin/apolipoprotein J was associated with atrophy of the entorhinal cortex, baseline disease severity, and rapid clinical progression in AD. Increased plasma concentration of clusterin was predictive of greater fibrillar amyloid-beta burden in the medial temporal lobe. Subjects with AD had increased clusterin messenger RNA in blood, but there was no effect of single-nucleotide polymorphisms in the gene encoding clusterin with gene or protein expression. APP/PS1 transgenic mice showed increased plasma clusterin, age-dependent increase in brain clusterin, as well as amyloid and clusterin colocalization in plaques. CONCLUSIONS: These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.EU as part of the FP6 InnoMed programmeAlzheimer's Research TrustNIHR Biomedical Research Centre for Mental Health at the South London and
Maudsley NHS Foundation Trust and King's College LondonBUPA FoundationAlzheimer's Societ
A high-risk study of bipolar disorder. Childhood clinical phenotypes as precursors of major mood disorders

CONTEXT:

The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy.

OBJECTIVE:

To report the lifetime prevalence and early clinical predictors of psychiatric disorders in offspring from families of probands with DSM-IV BP compared with offspring of control subjects.

DESIGN:

A longitudinal, prospective study of individuals at risk for BP and related disorders. We report initial (cross-sectional and retrospective) diagnostic and clinical characteristics following best-estimate procedures.

SETTING:

Assessment was performed at 4 university medical centers in the United States between June 1, 2006, and September 30, 2009.

PARTICIPANTS:

Offspring aged 12 to 21 years in families with a proband with BP (n = 141, designated as cases) and similarly aged offspring of control parents (n = 91).

MAIN OUTCOME MEASURE:

Lifetime DSM-IV diagnosis of a major affective disorder (BP type I; schizoaffective disorder, bipolar type; BP type II; or major depression).

RESULTS:

At a mean age of 17 years, cases showed a 23.4% lifetime prevalence of major affective disorders compared with 4.4% in controls (P = .002, adjusting for age, sex, ethnicity, and correlation between siblings). The prevalence of BP in cases was 8.5% vs 0% in controls (adjusted P = .007). No significant difference was seen in the prevalence of other affective, anxiety, disruptive behavior, or substance use disorders. Among case subjects manifesting major affective disorders (n = 33), there was an increased risk of anxiety and externalizing disorders compared with cases without mood disorder. In cases but not controls, a childhood diagnosis of an anxiety disorder (relative risk = 2.6; 95% CI, 1.1-6.3; P = .04) or an externalizing disorder (3.6; 1.4-9.0; P = .007) was predictive of later onset of major affective disorders.

CONCLUSIONS:

Childhood anxiety and externalizing diagnoses predict major affective illness in adolescent offspring in families with probands with BP
Functional Brain Basis of Hypnotizability

Context Focused hypnotic concentration is a model for brain control over sensation and behavior. Pain and anxiety can be effectively alleviated by hypnotic suggestion, which modulates activity in brain regions associated with focused attention, but the specific neural network underlying this phenomenon is not known.

Objective To investigate the brain basis of hypnotizability.

Design Cross-sectional, in vivo neuroimaging study performed from November 2005 through July 2006.

Setting Academic medical center at Stanford University School of Medicine.

Patients Twelve adults with high and 12 adults with low hypnotizability.

Main Outcome Measures Functional magnetic resonance imaging to measure functional connectivity networks at rest, including default-mode, salience, and executive-control networks; structural T1 magnetic resonance imaging to measure regional gray and white matter volumes; and diffusion tensor imaging to measure white matter microstructural integrity.

Results High compared with low hypnotizable individuals had greater functional connectivity between the left dorsolateral prefrontal cortex, an executive-control region of the brain, and the salience network composed of the dorsal anterior cingulate cortex, anterior insula, amygdala, and ventral striatum, involved in detecting, integrating, and filtering relevant somatic, autonomic, and emotional information using independent component analysis. Seed-based analysis confirmed elevated functional coupling between the dorsal anterior cingulate cortex and the dorsolateral prefrontal cortex in high compared with low hypnotizable individuals. These functional differences were not due to any variation in brain structure in these regions, including regional gray and white matter volumes and white matter microstructure.

Conclusions Our results provide novel evidence that altered functional connectivity in the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex may underlie hypnotizability. Future studies focusing on how these functional networks change and interact during hypnosis are warranted
Epidemiology of autism spectrum disorders in adults in the community in England

Context  To our knowledge, there is no published information on the epidemiology of autism spectrum disorders (ASDs) in adults. If the prevalence of autism is increasing, rates in older adults would be expected to be lower than rates among younger adults. \ud
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Objective  To estimate the prevalence and characteristics of adults with ASD living in the community in England. \ud
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Design  A stratified, multiphase random sample was used in the third national survey of psychiatric morbidity in adults in England in 2007. Survey data were weighted to take account of study design and nonresponse so that the results were representative of the household population. \ud
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Setting  General community (ie, private households) in England. \ud
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Participants  Adults (people 16 years or older). \ud
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Main Outcome Measures  Autism Diagnostic Observation Schedule, Module 4 in phase 2 validated against the Autism Diagnostic Interview–Revised and Diagnostic Interview for Social and Communication Disorders in phase 3. A 20-item subset of the Autism-Spectrum Quotient self-completion questionnaire was used in phase 1 to select respondents for phase 2. Respondents also provided information on sociodemographics and their use of mental health services. \ud
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Results  Of 7461 adult participants who provided a complete phase 1 interview, 618 completed phase 2 diagnostic assessments. The weighted prevalence of ASD in adults was estimated to be 9.8 per 1000 (95% confidence interval, 3.0-16.5). Prevalence was not related to the respondent's age. Rates were higher in men, those without educational qualifications, and those living in rented social (government-financed) housing. There was no evidence of increased use of services for mental health problems. \ud
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Conclusions  Conducting epidemiologic research on ASD in adults is feasible. The prevalence of ASD in this population is similar to that found in children. The lack of an association with age is consistent with there having been no increase in prevalence and with its causes being temporally constant. Adults with ASD living in the community are socially disadvantaged and tend to be unrecognized.Peer-reviewe
Neuroanatomical abnormalities that predate the onset of psychosis : a multicenter study

People experiencing possible prodromal symptoms of psychosis have a very high risk of developing the disorder, but it is not possible to predict, on the basis of their presenting clinical features, which individuals will subsequently become psychotic. Recent neuroimaging studies suggest that there are volumetric differences between individuals at ultra-high risk (UHR) for psychosis who later develop psychotic disorder and those who do not. However, the samples examined to date have been small, and the findings have been inconsistent
Thalamic glutamate levels as a predictor of cortical response during executive functioning in subjects at high risk for psychosis

CONTEXT:\ud
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Alterations in glutamatergic neurotransmission and cerebral cortical dysfunction are thought to be central to the pathophysiology of psychosis, but the relationship between these 2 factors is unclear.\ud
OBJECTIVE:\ud
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To investigate the relationship between brain glutamate levels and cortical response during executive functioning in people at high risk for psychosis (ie, with an at-risk mental state [ARMS]).\ud
DESIGN:\ud
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Subjects were studied using functional magnetic resonance imaging while they performed a verbal fluency task, and proton magnetic resonance spectroscopy was used to measure their brain regional glutamate levels.\ud
SETTING:\ud
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Maudsley Hospital, London, England. Patients and Other\ud
PARTICIPANTS:\ud
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A total of 41 subjects: 24 subjects with an ARMS and 17 healthy volunteers (controls).\ud
MAIN OUTCOME MEASURES:\ud
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Regional brain activation (blood oxygen level-dependent response); levels of glutamate in the anterior cingulate, left thalamus, and left hippocampus; and psychopathology ratings at the time of scanning.\ud
RESULTS:\ud
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During the verbal fluency task, subjects with an ARMS showed greater activation than did controls in the middle frontal gyrus bilaterally. Thalamic glutamate levels were lower in the ARMS group than in control group. Within the ARMS group, thalamic glutamate levels were negatively associated with activation in the right dorsolateral prefrontal and left orbitofrontal cortex, but positively associated with activation in the right hippocampus and in the temporal cortex bilaterally. There was also a significant group difference in the relationship between cortical activation and thalamic glutamate levels, with the control group showing correlations in the opposite direction to those in the ARMS group in the prefrontal cortex and in the right hippocampus and superior temporal gyrus.\ud
CONCLUSIONS:\ud
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Altered prefrontal, hippocampal, and temporal function in people with an ARMS is related to a reduction in thalamic glutamate levels, and this relationship is different from that in healthy controls
Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies

Context: Polymorphisms in the gene encoding the glucocorticoid receptor (GR) regulating co-chaperone FKBP5 have been shown to alter GR sensitivity and are associated with an increased risk to develop posttraumatic stress disorder (PTSD). Objective: To investigate interactions of the FKBP5 single-nucleotide polymorphism rs9296158 and PTSD symptoms on baseline cortisol level, low-dose dexamethasone suppression, and whole-blood gene expression. Design: Association of FKBP5 genotypes and PTSD symptoms with endocrine measures and genome-wide expression profiles. Setting: Waiting rooms of general medical and gynecological clinics of an urban hospital at Emory University. Participants: The 211 participants were primarily African American (90.05%) and of low socioeconomic status and had high rates of trauma and PTSD. Main Outcome Measures: Baseline and post-dexamethasone suppression cortisol measures and gene expression levels. Results: In our endocrine study, we found that only risk allele A carriers of rs9296158 showed GR supersensitivity with PTSD; in contrast, baseline cortisol levels were decreased in PTSD only in patients with the GG genotype. Expression of 183 transcripts was significantly correlated with PTSD symptoms after multiple testing corrections. When adding FKBP5 genotype and its interaction with PTSD symptoms, expression levels of an additional 32 genes were significantly regulated by the interaction term. Within these 32 genes, previously reported PTSD candidates were identified, including FKBP5 and the IL18 and STAT pathways. Significant overrepresentation of steroid hormone transcription factor binding sites within these 32 transcripts was observed, highlighting the fact that the earlier-described genotype and PTSDdependent differences in GR sensitivity could drive the observed gene expression pattern. Results were validated by reverse transcriptase-polymerase chain reaction and replicated in an independent sample (N=98). Conclusions: These data suggest that the inheritance of GR sensitivity-moderating FKBP5 polymorphisms can determine specific types of hypothalamic-pituitaryadrenal axis dysfunction within PTSD, which are also reflected in gene-expression changes of a subset of GRresponsive genes. Thus, these findings indicate that functional variants in FKBP5 are associated with biologically distinct subtypes of PTSD
Acute coronary syndrome: what do patients know?

Background: The effectiveness of therapy for an acute coronary syndrome (ACS) is dependent on patients' quick decision to seek treatment. We surveyed patients' level of knowledge about heart disease and self-perceived risk for a future acute myocardial infarction (AMI) in patients with documented ischemic heart disease. Methods: Patients (N = 3522) had a mean age of 67 years, 68% were male, and all had a history of AMI or invasive cardiac procedure for ischemic heart disease. Data were gathered using a 26-item instrument focusing on ACS symptoms and appropriate steps to seeking treatment. Patients were asked to identify their level of perceived risk for a future AMI. Results: Forty-six percent of patients had low knowledge levels (ie, <70% of answers were correct). The mean score was 71%. Higher knowledge scores were significantly related to female sex (P = .001), younger age (P = .001), higher education (P = .001), participation in cardiac rehabilitation (P = .001), and receiving care by a cardiologist rather than an internist or general practitioner (P = .005). Clinical history (eg, AMI [P = .24] and cardiac surgery [P = .38]) were not significant predictors of knowledge. Most (57%) identified themselves as being at higher risk for a future AMI compared with an age-matched individual without heart disease with 1 exception. Namely, patients who had undergone coronary artery bypass surgery felt significantly less vulnerable for a future AMI than other individuals of the same age. Conclusions: Even following diagnosis of ACS and numerous interactions with physicians and other health care professionals, knowledge about ACS symptoms and treatment on the part of patients with cardiac disease remains poor. Patients require continued reinforcement about the nature of cardiac symptoms, the benefits of early treatment, and their risk status
Characterization of resistant hypertension: Association between resistant hypertension, aldosterone, and persistent intravascular volume expansion

Background: Resistant hypertension is a common clinical problem and greatly increases the risk of target organ damage. Methods: We evaluated the characteristics of 279 consecutive patients with resistant hypertension (uncontrolled despite the use of 3 antihypertensive agents) and 53 control subjects (with normotension or hypertension controlled by using ≤2 antihypertensive medications). Participants were prospectively examined for plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, brain-type natriuretic peptide, atrial natriuretic peptide, and 24-hour urinary aldosterone (UAldo), cortisol, sodium, and potassium values while adhering to a routine diet. Results: Plasma aldosterone (P < .001), aldosterone to renin ratio (P < .001), 24-hour UAldo (P = .02), brain-type natriuretic peptide (P = .007), and atrial natriuretic peptide (P = .001) values were higher and plasma renin activity (P = .02) and serum potassium (P < .001) values were lower in patients with resistant hypertension vs controls. Of patients with resistant hypertension, men had significantly higher plasma aldosterone (P = .003), aldosterone to renin ratio (P = .02), 24-hour UAldo (P < .001), and urinary cortisol (P < .001) values than women. In univariate linear regression analysis, body mass index (P = .01), serum potassium (P < .001), urinary cortisol (P < .001), urinary sodium (P = .02), and urinary potassium (P < .001) values were correlated with 24-hour UAldo levels. Serum potassium (P = .001), urinary potassium (P < .001), and urinary sodium (P = .03) levels were predictors of 24-hour UAldo levels in multivariate modeling. Conclusions: Aldosterone levels are higher and there is evidence of intravascular volume expansion (higher brain-type and atrial natriuretic peptide levels) in patients with resistant hypertension vs controls. These differences are most pronounced in men. A significant correlation between 24-hour urinary aldosterone levels and cortisol excretion suggests that a common stimulus, such as corticotropin, may underlie the aldosterone excess in patients with resistant hypertension
Measurement of renin in both renal veins: its use in diagnosis of renovascular hypertension

THE RECENT development of a simple reliable method for measuring plasma renin activity, together with the availability of a safe procedure for obtaining samples of blood from both renal veins, has prompted us to assess the utility of such measurements in the diagnosis of surgically correctable renovascular hypertension. Previous studies of this type have been reported by McPhaul,1 Fitz,2 Kirkendall,3 and Ueda,4 and their associates. A series of 22 patients, diagnosed by conventional measures as having renovascular hypertension, were subjected to operative treatment. Proof of the diagnosis was considered to be established if there was unquestionable improvement in blood pressure after corrective surgery. This is a report of the measurements of renin activity in blood plasma specimens obtained from both renal veins preoperatively and, whenever possible, postoperatively. In addition, plasma renin activity in effluent blood from both kidneys was measured in 13 patients with "essential" hypertension, who were not subjecte
Hypernatremia: Complication of Renal Homotransplantation

Hypernatremia was observed in five recipients of renal homografts during the first postoperative week. The peak serum levels of sodium varied between 152 and 158 mEq/liter. The postoperative diuresis was associated with sodium concentration in the urine, consistently lower than that in the extracellular water; moderate urinary hypertonicity, with urea being the main urinary solute; and urea excretion exceeding 60% of its filtered load in most instances. The inability of elaborate urine with sodium concentration equal or higher than that in the serum, possibly related to osmotic diuresis and/or altered renal hemodynamics, appears to be the primary cause responsible for the development of hypernatremia in these patients. © 1971, American Medical Association. All rights reserved
Immune-responses to varicella-zoster in the aged

Skin test reactivity and in vitro lymphocyte stimulation responses to varicella-zoster (VZ) were examined in a large normal population ranging in age from 6 months to 93 years. Waning of cellular immunity, as examined by skin delayed hypersensitivity, began at age 40 years. Skin test responses to phytohemagglutinin, however, remained positive into the eighth decade of life. In vitro lymphocyte stimulation responses to VZ were usually positive (stimulation index ≥2.5) until age 60 years, after which time levels, as observed with nonimmune individuals, were often demonstrated. Antibody levels, as measured by fluorescent antibody to membrane antigen, remained positive into the ninth and tenth decades of life. This was especially so with a history of reactivation (zoster) VZ infections, while skin test and in vitro responses were rarely positive in those individuals. Thus cellular, as contrasted with humoral, immunity decreases with advancing age, which may account for a propensity to reactivation of VZ virus
Clinical and hemodynamic determinants of left ventricular dimensions

This study was designed to quantitate the influence of 20 clinical, hemodynamic, and volume determinants of left ventricular (LV) structure. Systemic hemodynamics, intravascular volume, and LV echocardiographic measurements were collected in a heterogeneous population of 171 patients. Stepwise multiple-regression analysis indicated that body weight and body-surface area were the most powerful determinants of LV chamber size, wall thickness, and muscle mass. Age, a pressure independent determinant of myocardial mass, had no influence on chamber size or LV function. Arterial pressure correlated best with the relative wall thickness and chamber volume. Intravascular volume was a major discriminator for chamber volume, LV mass, and velocity of circumferential fiber shortening. It is concluded that body weight, arterial pressure, intravascular volume, and age are each independent determinants of the LV dimension. Systolic pressure most closely correlated with relative wall thickness and thereby is the best predictor of degree of concentric LV hypertrophy