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  • 1
    Publication Date: 2013-12-20
    Description: In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stefansson, Hreinn -- Meyer-Lindenberg, Andreas -- Steinberg, Stacy -- Magnusdottir, Brynja -- Morgen, Katrin -- Arnarsdottir, Sunna -- Bjornsdottir, Gyda -- Walters, G Bragi -- Jonsdottir, Gudrun A -- Doyle, Orla M -- Tost, Heike -- Grimm, Oliver -- Kristjansdottir, Solveig -- Snorrason, Heimir -- Davidsdottir, Solveig R -- Gudmundsson, Larus J -- Jonsson, Gudbjorn F -- Stefansdottir, Berglind -- Helgadottir, Isafold -- Haraldsson, Magnus -- Jonsdottir, Birna -- Thygesen, Johan H -- Schwarz, Adam J -- Didriksen, Michael -- Stensbol, Tine B -- Brammer, Michael -- Kapur, Shitij -- Halldorsson, Jonas G -- Hreidarsson, Stefan -- Saemundsen, Evald -- Sigurdsson, Engilbert -- Stefansson, Kari -- G0701748/Medical Research Council/United Kingdom -- England -- Nature. 2014 Jan 16;505(7483):361-6. doi: 10.1038/nature12818. Epub 2013 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland [2]. ; 1] Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany [2]. ; deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland. ; Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavik, Iceland. ; Central Institute of Mental Health, University of Heidelberg Medical Faculty Mannheim, 68159 Mannheim, Germany. ; 1] deCODE genetics/Amgen, Sturlugata 8, IS-101 Reykjavik, Iceland [2] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavik, Iceland. ; Institute of Psychiatry, King's College, 16 De Crespigny Park, London SE5 8AF, UK. ; 1] Landspitali, Department of Psychiatry, National University Hospital, IS-101 Reykjavik, Iceland [2] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; Rontgen Domus, Egilsgotu 3, IS-101 Reykjavik, Iceland. ; Mental Health Centre Sct. Hans, Copenhagen University Hospital, Research Institute of Biological Psychiatry, Boserupvej 2, DK-4000 Roskilde, Denmark. ; Tailored Therapeutics, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center DC 1940, Indianapolis, Indiana 46285, USA. ; H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. ; University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland. ; The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kopavogur, Iceland. ; 1] University of Iceland, Faculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland [2] The State Diagnostic and Counselling Centre, Digranesvegur 5, IS-200 Kopavogur, Iceland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352232" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Aged ; Autistic Disorder/*genetics ; Brain/abnormalities/anatomy & histology/metabolism ; Case-Control Studies ; Chromosome Deletion ; Chromosomes, Human/genetics ; Chromosomes, Human, Pair 15/genetics ; Cognition/*physiology ; DNA Copy Number Variations/*genetics ; Dyslexia/genetics ; Female ; Fertility/genetics ; *Genetic Predisposition to Disease ; Heterozygote ; Humans ; Iceland ; Learning Disorders/genetics ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuropsychological Tests ; Phenotype ; Schizophrenia/*genetics ; Young Adult
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2011-06-24
    Description: More than half of the world's population now lives in cities, making the creation of a healthy urban environment a major policy priority. Cities have both health risks and benefits, but mental health is negatively affected: mood and anxiety disorders are more prevalent in city dwellers and the incidence of schizophrenia is strongly increased in people born and raised in cities. Although these findings have been widely attributed to the urban social environment, the neural processes that could mediate such associations are unknown. Here we show, using functional magnetic resonance imaging in three independent experiments, that urban upbringing and city living have dissociable impacts on social evaluative stress processing in humans. Current city living was associated with increased amygdala activity, whereas urban upbringing affected the perigenual anterior cingulate cortex, a key region for regulation of amygdala activity, negative affect and stress. These findings were regionally and behaviourally specific, as no other brain structures were affected and no urbanicity effect was seen during control experiments invoking cognitive processing without stress. Our results identify distinct neural mechanisms for an established environmental risk factor, link the urban environment for the first time to social stress processing, suggest that brain regions differ in vulnerability to this risk factor across the lifespan, and indicate that experimental interrogation of epidemiological associations is a promising strategy in social neuroscience.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lederbogen, Florian -- Kirsch, Peter -- Haddad, Leila -- Streit, Fabian -- Tost, Heike -- Schuch, Philipp -- Wust, Stefan -- Pruessner, Jens C -- Rietschel, Marcella -- Deuschle, Michael -- Meyer-Lindenberg, Andreas -- England -- Nature. 2011 Jun 22;474(7352):498-501. doi: 10.1038/nature10190.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, 68159 Mannheim, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21697947" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*physiology ; Anxiety Disorders/epidemiology ; *Cities/epidemiology ; Gyrus Cinguli/*physiology ; Humans ; Hydrocortisone/blood ; *Life Style ; Magnetic Resonance Imaging ; Mental Health/statistics & numerical data ; Models, Neurological ; Mood Disorders/epidemiology ; Rural Health/statistics & numerical data ; Sample Size ; Schizophrenia/epidemiology ; Stress, Psychological/blood/epidemiology/*physiopathology ; Time Factors ; Urban Health/statistics & numerical data ; Urbanization
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  51. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie; 20060910-20060914; Leipzig; DOC06gmds442 /20060901/
    Publication Date: 2006-09-25
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 4
    ISSN: 1432-2013
    Keywords: Dehydration ; Glomerular Filtration Rate ; Isolated Kidney
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The two kidneys of one dog were perfused separately with the same blood pool and at a constant arterial pressure. After the control periods, one of the kidneys was replaced by another one taken from a dehydrated dog. The presence of the “dehydrated” kidney resulted in significant and almost immediate decreases of creatinin clearance, urine flow and sodium excretion by the contralateral kidney, without any change in the overall renal blood flow. These changes disappeared, after the removal of the “dehydrated” kidney. They were not observed if the “dehydrated” kidney was replaced either by a kidney taken from a salt-depleted, non water-deprived dog, or by a simple arterio-venous shunt. These results suggest that in the status of dehydration, the kidney releases some humoral material which might be responsible for the decrease of the measured GFR (C creat) perhaps by the way of permeability changes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2013
    Keywords: Sodium Excretion ; Natriuretic Factors ; Transplanted Kidneys
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The increase in fractional excretion of sodium following intravenous infusion of saline has been investigated in dogs fed with sodium-rich or poor diets after transplantation to the neck of these animals of kidneys removed from dogs submitted previously to either diet. The response of “in situ” and of transplanted organs has been compared in the four possible combinations of perfusors and kidney donors. No significant differences were observed between the four series, for the same net saline load, in arterial and venous pressures, extravascular and intravascular expansion, or blood dilution. The response in each series was independent of extracellular expansion and was best related to the degree of blood dilution. However, the magnitude of the response to the same net saline load depended on a resetting of the sensitivity of the kidney itself to the blood changes, this resetting depending on the previous dietary sodium balance. This sensitivity was related also to the presence in the blood of a potentiating material which might be, at least partly, of renal origin, and which might represent an intrarenal mediator of the natriuretic response.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-2584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of ethyl alcohol infused directly via the renal artery and by the venous route were studied on the renal function in 10 anaesthetized dogs with the following results: 1) Ethyl alcohol lowers blood pressure. The hypotensive effect is more marked on direct renal arterial than on intravenous infusion. 2) Ethyl alcohol dilates the renal blood vessels parallel with a fall in total renal vascular resistance. 3) Ethyl alcohol reduces the glomerular filtration rate in the anaesthetized dog, as reflected by a reduction in the values of CPAH and Ccreat. 4) Infusion of ethyl alcohol was accompanied by a decrease in the renal excretion of water and sodium, in all likelihood due to an impairment of glomerular function. The results seem to indicate that the effect of ethyl alcohol on the kidney is associated with a readjustment of renal function to a new glomerulo-tubular equilibrium at a reduced level.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-2584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The functional parameters of renal function of non-hydrated and hydrated dogs (saline-infused to an extent of 1–2% of the body weight) have been compared. The directly measured renal blood flow and the total renal vascular resistance were the same in the two groups. No difference has been found in glomerular filtration rate, theC inulin was the same in the two groups. There was no important difference in the PAH clearance and PAH extraction. In the hypervolaemic group, the sodium and water excretion was about threefold that of the non-hydrated animals. The plasma protein concentration was significantly lower in the hydrated group. In our experiments we did not find glomerular factors responsible for the increase of sodium and water excretion. The decrease of tubular reabsorption is attributed partly to the decreased plasma protein concentration, partly to unknown (perhaps natriuretic) humoral factors.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    International urology and nephrology 3 (1971), S. 271-282 
    ISSN: 1573-2584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of angiotensin infused via the renal artery, and subsequently by the venous route, have been studied on the renal function in anaesthetized dogs. 1. Infusion of angiotensin into the renal artery in large doses (0.5 or 1.0 μg per min) produces a fall in the parameters of renal function to a certain level which even more massive doses fail to lower any further. 2. Infusion of angiotensin reduces PAH- and creatinine clearances as well as the excretion of water and sodium. 3. The angiotensin-induced impairment of renal function is attributed to glomerular changes. The results of the present study rule out tubular involvement. 4. The blood pressure changes resulting from administration of angiotensin by the intravenous route are connected with a prompt tachyphylactic effect. 5. In the present study no angiotensin-tachyphylaxis was demonstrable in the renal vessels. 6. The angiotensin-induced retention of sodium and water may reduce the therapeutic value of this substance.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    International urology and nephrology 3 (1971), S. 437-440 
    ISSN: 1573-2584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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