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1.
  • Forouzanfar, Mohammad H, et al. (författare)
  • Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
  • 2015
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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2.
  • Vos, Theo, et al. (författare)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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3.
  • Weinstein, John N., et al. (författare)
  • The cancer genome atlas pan-cancer analysis project
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
  • Forskningsöversikt (refereegranskat)abstract
    • The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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4.
  • Brooks, Samantha J, et al. (författare)
  • Late-life obesity is associated with smaller global and regional gray matter volumes : a voxel-based morphometric study
  • 2013
  • Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37:2, s. 230-236
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes.DESIGN: Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task.SUBJECTS: A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m−2) or obese (30 kg m−2).RESULTS: People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight.CONCLUSION: These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.
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5.
  • Chye, Yann, et al. (författare)
  • Subcortical surface morphometry in substance dependence : An ENIGMA addiction working group study
  • 2020
  • Ingår i: Addiction Biology. - : WILEY. - 1355-6215 .- 1369-1600. ; 25:6
  • Tidskriftsartikel (refereegranskat)abstract
    • While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.
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6.
  • Heany, Sarah J., et al. (författare)
  • A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain
  • 2016
  • Ingår i: Metabolic brain disease. - : Springer Science and Business Media LLC. - 0885-7490 .- 1573-7365. ; 31:1, s. 157-167
  • Tidskriftsartikel (refereegranskat)abstract
    • Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.
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7.
  • Neville, George M., et al. (författare)
  • Interactions of Choline and Geranate (CAGE) and Choline Octanoate (CAOT) Deep Eutectic Solvents with Lipid Bilayers
  • 2023
  • Ingår i: Advanced Functional Materials. - 1616-301X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Mixtures between choline and geranic acid (CAGE) have previously been shown to insert into lipid bilayers. This may be useful for the transdermal delivery of larger pharmaceuticals, however, little is known about the mechanism of activity. By comparing the interactions between CAGE and lipid bilayers with those of a less-active, yet closely-related analogue, choline octanoic acid (CAOT), a chemical basis can be investigated. Overall, six systems are studied here by neutron reflectivity, where d54-1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) solid-supported phospholipid bilayers are first formed on SiO2 substrates before exposure to the deep eutectic solvent (DES). Components of the DES could be identified within the bilayer by exploiting contrast variation and selective deuteration. CAGE is shown to be a mild disruptive agent, free to insert and diffuse across the bilayer, preserving much of the bilayer integrity. Experiments identify co-mingling of geranate ions inhibits the efficient packing of lipid tails, increasing hydration across the bilayer. Conversely, CAOT is found to both exchange and remove lipid molecules to achieve incorporation, inducing swelling and the formation of solvent patches. It appears these behaviors derive from the structures of the anions and thus amphiphilicity of the DES, laying the foundations for the rational design and optimization of these candidates toward transdermal delivery.
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8.
  • Benedict, Christian, et al. (författare)
  • Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly
  • 2012
  • Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:3, s. 488-494
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVEImpaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.RESEARCH DESIGN AND METHODSInsulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).RESULTSThe HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.CONCLUSIONSThese cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.
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9.
  • Brooks, Samantha J, et al. (författare)
  • BDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1, s. e82707-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Brain-derived neurotrophic factor (BDNF) links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking.METHODS: 367 elderly Swedish men (n = 181) and women (n = 186) from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS) were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT), verbal fluency task, and had a magnetic resonance imaging (MRI) scan. Voxel-based morphometry (VBM) examined brain structure, cognition and links with BDNF.RESULTS: The functional BDNF SNP (rs6265,) predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes.CONCLUSIONS: The functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly.
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10.
  • Brooks, Samantha J, et al. (författare)
  • Early-life adversity and orbitofrontal and cerebellar volumes in adults with obsessive-compulsive disorder : voxel-based morphometry study.
  • 2016
  • Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 208:1, s. 34-41
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Early-life adversity is a risk for obsessive-compulsive disorder (OCD), but the impact at the neural level is less clear.AIMS: To investigate the association between brain volumes and early-life adversity in individuals with a diagnosis of OCD only.METHOD: The Childhood Trauma Questionnaire (CTQ-28) was used to assess early-life adversity in 21 participants with OCD and 25 matched healthy controls. The relationship between global and regional brain volume and early-life adversity was measured using voxel-based morphometry (VBM). All data were corrected for multiple comparisons using family-wise error (FWE) at P<0.05.RESULTS: In the OCD group, correlations with total CTQ scores were positively associated with a larger right orbitofrontal cortex volume. Physical neglect was higher in the OCD group than in controls and was positively associated with larger right cerebellum volume in the OCD group only.CONCLUSIONS: Larger brain volumes may reflect underlying developmental neuropathology in adults with OCD who also have experience of childhood trauma.
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11.
  • Brooks, Samantha J, et al. (författare)
  • Restraint of appetite and reduced regional brain volumes in anorexia nervosa : a voxel-based morphometric study
  • 2011
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 11, s. 179-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Previous Magnetic Resonance Imaging (MRI) studies of people with anorexia nervosa (AN) have shown differences in brain structure. This study aimed to provide preliminary extensions of this data by examining how different levels of appetitive restraint impact on brain volume.METHODS:Voxel based morphometry (VBM), corrected for total intracranial volume, age, BMI, years of education in 14 women with AN (8 RAN and 6 BPAN) and 21 women (HC) was performed. Correlations between brain volume and dietary restraint were done using Statistical Package for the Social Sciences (SPSS).RESULTS:Increased right dorsolateral prefrontal cortex (DLPFC) and reduced right anterior insular cortex, bilateral parahippocampal gyrus, left fusiform gyrus, left cerebellum and right posterior cingulate volumes in AN compared to HC. RAN compared to BPAN had reduced left orbitofrontal cortex, right anterior insular cortex, bilateral parahippocampal gyrus and left cerebellum. Age negatively correlated with right DLPFC volume in HC but not in AN; dietary restraint and BMI predicted 57% of variance in right DLPFC volume in AN.CONCLUSIONS:In AN, brain volume differences were found in appetitive, somatosensory and top-down control brain regions. Differences in regional GMV may be linked to levels of appetitive restraint, but whether they are state or trait is unclear. Nevertheless, these discrete brain volume differences provide candidate brain regions for further structural and functional study in people with eating disorders.
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12.
  • Brooks, Samantha J., et al. (författare)
  • The impact of cognitive training in substance use disorder : the effect of working memory training on impulse control in methamphetamine users
  • 2017
  • Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 234:12, s. 1911-1921
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Impulsivity is a vulnerability trait for poor self-regulation in substance use disorder (SUD). Working memory (WM) training improves impulsivity and self-regulation in psychiatric disorders. Here we test WM training in methamphetamine use disorder (MUD).METHODS: There are 15 MUD patients receiving inpatient treatment as usual (TAU) and 20 who additionally completed WM cognitive training (CT) and 25 healthy controls (HC). MANCOVA repeated measures analyses examined changes in impulsivity and self-regulation at baseline and after 4 weeks.RESULTS:  = 0.3523, p < 0.05). Compared to follow-up TAU, follow-up CT group had higher self-reported mood scores (t = 2.784, p = 0.01) and higher compared to CT baseline (t = 2.386, p = 0.036). Feelings of self-control were higher in CT than TAU at follow-up (t = 2.736, p = 0.012) and also compared to CT baseline (t = 3.390, p = 0.006), lack of planning significantly improved in CT between baseline and follow-up (t = 2.219, p = 0.048), as did total impulsivity scores (t = 2.085, p = 0.048). Measures of self-regulation were improved in the CT group compared to TAU at follow-up, in total score (t = 2.442, p = 0.038), receiving score (t = 2.314, p = 0.029) and searching score (t = 2.362, p = 0.027). Implementing self-regulation was higher in the CT group compared to TAU (t = 2.373, p = 0.026).CONCLUSIONS: WM training may improve control of impulsivity and self-regulation in people with MUD.
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13.
  • Burger, Antoinette, et al. (författare)
  • The impact of acute and short-term methamphetamine abstinence on brain metabolites : A proton magnetic resonance spectroscopy chemical shift imaging study
  • 2018
  • Ingår i: Drug And Alcohol Dependence. - : Elsevier BV. - 0376-8716 .- 1879-0046. ; 185, s. 226-237
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAbuse of methamphetamine (MA) is a global health concern. Previous H-1-MRS studies have found that, with methamphetamine abstinence (MAA), there are changes in n-acetyl-aspartate (NAA/Cr), myo-inositol (mI/Cr), choline (Cho/Cr and Cho/NAA), and glutamate with glutamine (Glx) metabolites. Limited studies have investigated the effect of acute MAA, and acute-to-short-term MAA on brain metabolites.MethodsAdults with chronic MA dependence (n = 31) and healthy controls (n = 22) were recruited. Two-dimensional chemical shift H-1-MRS imaging (TR2000 ms, TE30 ms) slice was performed and included voxels in bilateral anterior-cingulate (ACC), frontal-white-matter (FWM), and dorsolateral-prefrontal-cortices (DLPFC). Control participants were scanned once. The MA group was scanned twice, with acute (1.5 +/- 0.6 weeks, n = 31) and short-term MAA (5.1 +/- 0.8 weeks, n = 22). The change in H-1-MRS metabolites over time (n = 19) was also investigated. Standard H-1-MRS metabolites are reported relative to Cr + PCr.ResultsAcute MAA showed lower n-acetyl-aspartate (NAA) and n-acetyl-aspartate with n-acetyl-aspartyl-glutamate (NAA + NAAG) in left DLPFC, and glycerophosphocholine with phosphocholine (GPC + PCh) in left FWM. Short-term MAA showed lower NAA + NAAG and higher myo-inositol (mI) in right ACC, lower NAA and NAA + NAAG in the left DLPFC, and lower GPC + PCh in left FWM. Over time, MAA showed decreased NAA and NAA + NAAG and increased mI in right ACC, decreased NAA and NAA + NAAG in right FWM, and decreased in mI in left FWM.ConclusionIn acute MAA, there was damage to the integrity of neuronal tissue, which was enhanced with short-term MAA. From acute to short-term MAA, activation of neuroinflammatory processes are suggested. This is the first H-1-MRS study to report the development of neuroinflammation with loss of neuronal integrity in MAA.
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14.
  • Dalvie, Shareefa, et al. (författare)
  • The BDNF p.Val66Met polymorphism, childhood trauma, and brain volumes in adolescents with alcohol abuse
  • 2014
  • Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Previous studies have indicated that early life adversity, genetic factors and alcohol dependence are associated with reduced brain volume in adolescents. However, data on the interactive effects of early life adversity, genetic factors (e.g. p.Met66 allele of BDNF), and alcohol dependence, on brain structure in adolescents is limited. We examined whether the BDNF p.Val66Met polymorphism interacts with childhood trauma to predict alterations in brain volume in adolescents with alcohol use disorders (AUDs).METHODS: We examined 160 participants (80 adolescents with DSM-IV AUD and 80 age- and gender-matched controls) who were assessed for trauma using the Childhood Trauma Questionnaire (CTQ). Magnetic resonance images were acquired for a subset of the cohort (58 AUD and 58 controls) and volumes of global and regional structures were estimated using voxel-based morphometry (VBM). Samples were genotyped for the p.Val66Met polymorphism using the TaqMan® Assay. Analysis of covariance (ANCOVA) and post-hoc t-tests were conducted using SPM8 VBM.RESULTS: No significant associations, corrected for multiple comparisons, were found between the BDNF p.Val66Met polymorphism, brain volumes and AUD in adolescents with childhood trauma.CONCLUSIONS: These preliminary findings suggest that the BDNF p.Met66 allele and childhood trauma may not be associated with reduced structural volumes in AUD. Other genetic contributors should be investigated in future studies.
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15.
  • Suda, Masashi, et al. (författare)
  • Functional Neuroanatomy of Body Checking in People with Anorexia Nervosa
  • 2013
  • Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 46:7, s. 653-662
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveThe neural correlates of body checking perceptions in eating disorders have not yet been identified. This functional Magnetic Resonance Imaging study examined the neuroanatomy involved in altered perception and identification with body checking in female with anorexia nervosa (AN). MethodBrain activation while viewing images depicting normal weight individuals involved in either body checking behavior or a neutral (noneating disorder) body action, was compared between 20 females with AN and 15 matched healthy controls (HC). ResultsFemales with AN reported higher anxiety compared to HC during the body checking task. The level of anxiety positively correlated with body shape concern scores. People with AN had less activation in the medial prefrontal cortex (PFC) and right fusiform gyrus compared to HC in response to body checking compared to neutral action images. Body shape concern scores correlated negatively with medial PFC activation in AN group. DiscussionThis preliminary study with modest power suggests that AN patients have reduced activation in cortical areas associated with self-reference, body action perception, and social cognition in females with AN.
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16.
  • Uhlmann, Anne, et al. (författare)
  • White matter volume alterations in hair-pulling disorder (trichotillomania)
  • 2020
  • Ingår i: Brain Imaging and Behavior. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 14:6, s. 2202-2209
  • Tidskriftsartikel (refereegranskat)abstract
    • Trichotillomania (TTM) is a disorder characterized by repetitive hair-pulling resulting in hair loss. Key processes affected in TTM comprise affective, cognitive, and motor functions. Emerging evidence suggests that brain matter aberrations in fronto-striatal and fronto-limbic brain networks and the cerebellum may characterize the pathophysiology of TTM. The aim of the present voxel-based morphometry (VBM) study was to evaluate whole brain grey and white matter volume alteration in TTM and its correlation with hair-pulling severity. High-resolution magnetic resonance imaging (3 T) data were acquired from 29 TTM patients and 28 age-matched healthy controls (CTRLs). All TTM participants completed the Massachusetts General Hospital Hair-Pulling Scale (MGH-HPS) to assess illness/pulling severity. Using whole-brain VBM, between-group differences in regional brain volumes were measured. Additionally, within the TTM group, the relationship between MGH-HPS scores, illness duration and brain volumes were examined. All data were corrected for multiple comparisons using family-wise error (FWE) correction at p < 0.05. Patients with TTM showed larger white matter volumes in the parahippocampal gyrus and cerebellum compared to CTRLs. Estimated white matter volumes showed no significant association with illness duration or MGH-HPS total scores. No significant between-group differences were found for grey matter volumes. Our observations suggest regional alterations in cortico-limbic and cerebellar white matter in patients with TTM, which may underlie deficits in cognitive and affective processing. Such volumetric white matter changes may precipitate impaired cortico-cerebellar communication leading to a reduced ability to control hair pulling behavior.
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17.
  • Benedict, Christian, et al. (författare)
  • Acute Sleep Deprivation Enhances the Brain's Response to Hedonic Food Stimuli : An fMRI Study
  • 2012
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:3, s. E443-447
  • Tidskriftsartikel (refereegranskat)abstract
    • Context:There is growing recognition that a large number of individuals living in Western society are chronically sleep deprived. Sleep deprivation is associated with an increase in food consumption and appetite. However, the brain regions that are most susceptible to sleep deprivation-induced changes when processing food stimuli are unknown.Objective:Our objective was to examine brain activation after sleep and sleep deprivation in response to images of food.Intervention:Twelve normal-weight male subjects were examined on two sessions in a counterbalanced fashion: after one night of total sleep deprivation and one night of sleep. On the morning after either total sleep deprivation or sleep, neural activation was measured by functional magnetic resonance imaging in a block design alternating between high- and low-calorie food items. Hunger ratings and morning fasting plasma glucose concentrations were assessed before the scan, as were appetite ratings in response to food images after the scan.Main Outcome Measures:Compared with sleep, total sleep deprivation was associated with an increased activation in the right anterior cingulate cortex in response to food images, independent of calorie content and prescan hunger ratings. Relative to the postsleep condition, in the total sleep deprivation condition, the activation in the anterior cingulate cortex evoked by foods correlated positively with postscan subjective appetite ratings. Self-reported hunger after the nocturnal vigil was enhanced, but importantly, no change in fasting plasma glucose concentration was found.Conclusions:These results provide evidence that acute sleep loss enhances hedonic stimulus processing in the brain underlying the drive to consume food, independent of plasma glucose levels. These findings highlight a potentially important mechanism contributing to the growing levels of obesity in Western society.
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18.
  • Benedict, Christian, et al. (författare)
  • Association between physical activity and brain health in older adults
  • 2013
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 34:1, s. 83-90
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present cross-sectional study, we examined physical activity (PA) and its possible association with cognitive skills and brain structure in 331 cognitively healthy elderly. Based on the number of self-reported light and hard activities for at least 30 minutes per week, participants were assigned to 4 groups representing different levels of PA. The cognitive skills were assessed by the Mini Mental State Examination score, a verbal fluency task, and the Trail-making test as a measure of visuospatial orientation ability. Participants also underwent a magnetic resonance imaging of the brain. Multiple regression analysis revealed that greater PA was associated with a shorter time to complete the Trail-making test, and higher levels of verbal fluency. Further, the level of self-reported PA was positively correlated with brain volume, white matter, as well as a parietal lobe gray matter volume, situated bilaterally at the precuneus. These present cross-sectional results indicate that PA is a lifestyle factor that is linked to brain structure and function in late life.
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19.
  • Benedict, Christian, et al. (författare)
  • Diurnal Rhythm of Circulating Nicotinamide Phosphoribosyltransferase (Nampt/Visfatin/PBEF) : Impact of Sleep Loss and Relation to Glucose Metabolism
  • 2012
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:2, s. E218-E222
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Animal studies indicate that nicotinamide phosphoribosyltransferase [Nampt/visfatin/pre-B-cell colony-enhancing factor (PBEF)] contributes to the circadian fine-tuning of metabolic turnover. However, it is unknown whether circulating Nampt concentrations, which are elevated in type 2 diabetes and obesity, display a diurnal rhythm in humans.Objective Our objective was to examine the 24-h profile of serum Nampt in humans under conditions of sleep and sleep deprivation and relate the Nampt pattern to morning postprandial glucose metabolism.InterventionFourteen healthy men participated in two 24-h sessions starting at 1800 h, including either regular 8-h-night sleep or continuous wakefulness. Serum Nampt and leptin were measured in 1.5- to 3-h intervals. In the morning, plasma glucose and serum insulin responses to standardized breakfast intake were determined.Main Outcome Measures Under regular sleep-wake conditions, Nampt levels displayed a pronounced diurnal rhythm, peaking during early afternoon (P < 0.001) that was inverse to leptin profiles peaking in the early night. When subjects stayed awake, the Nampt rhythm was preserved but phase advanced by about 2 h (P < 0.05). Two-hour postprandial plasma glucose concentrations were elevated after sleep loss (P < 0.05), whereas serum insulin was not affected. The relative glucose increase due to sleep loss displayed a positive association with the magnitude of the Nampt phase shift (r = 0.54; P < 0.05).ConclusionsSerum Nampt concentrations follow a diurnal rhythm, peaking in the afternoon. Sleep loss induces a Nampt rhythm phase shift that is positively related to the impairment of postprandial glucose metabolism due to sleep deprivation, suggesting a regulatory impact of Nampt rhythmicity on glucose homeostasis.
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20.
  • Brooks, Samantha J (författare)
  • A debate on working memory and cognitive control : can we learn about the treatment of substance use disorders from the neural correlates of anorexia nervosa?
  • 2016
  • Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Anorexia Nervosa (AN) is a debilitating, sometimes fatal eating disorder (ED) whereby restraint of appetite and emotion is concomitant with an inflexible, attention-to-detail perfectionist cognitive style and obsessive-compulsive behaviour. Intriguingly, people with AN are less likely to engage in substance use, whereas those who suffer from an ED with a bingeing component are more vulnerable to substance use disorder (SUD).DISCUSSION: This insight into a beneficial consequence of appetite control in those with AN, which is shrouded by the many other unhealthy, excessive and deficit symptoms, may provide some clues as to how the brain could be trained to exert better, sustained control over appetitive and impulsive processes. Structural and functional brain imaging studies implicate the executive control network (ECN) and the salience network (SN) in the neuropathology of AN and SUD. Additionally, excessive employment of working memory (WM), alongside more prominent cognitive deficits may be utilised to cope with the experience of negative emotions and may account for aberrant brain function. WM enables mental rehearsal of cognitive strategies while regulating, restricting or avoiding neural responses associated with the SN. Therefore, high versus low WM capacity may be one of the factors that unites common cognitive and behavioural symptoms in those suffering from AN and SUD respectively. Furthermore, emerging evidence suggests that by evoking neural plasticity in the ECN and SN with WM training, improvements in neurocognitive function and cognitive control can be achieved. Thus, considering the neurocognitive processes of excessive appetite control and how it links to WM in AN may aid the application of adjunctive treatment for SUD.
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21.
  • Brooks, Samantha J., et al. (författare)
  • Differential Neural Responses to Food Images in Women with Bulimia versus Anorexia Nervosa
  • 2011
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7, s. e22259-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results: In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.
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22.
  • Brooks, Samantha J., et al. (författare)
  • Exposure to subliminal arousing stimuli induces robust activation in the amygdala, hippocampus, anterior cingulate, insular cortex and primary visual cortex : A systematic meta-analysis of fMRI studies
  • 2012
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 59:3, s. 2962-2973
  • Forskningsöversikt (refereegranskat)abstract
    • Functional Magnetic Resonance Imaging (fMRI) demonstrates that the subliminal presentation of arousing stimuli can activate subcortical brain regions independently of consciousness-generating top-down cortical modulation loops. Delineating these processes may elucidate mechanisms for arousal, aberration in which may underlie some psychiatric conditions. Here we are the first to review and discuss four Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies using subliminal paradigms. We find a maximum of 9 out of 12 studies using subliminal presentation of faces contributing to activation of the amygdala, and also a significantly high number of studies reporting activation in the bilateral anterior cingulate, bilateral insular cortex, hippocampus and primary visual cortex. Subliminal faces are the strongest modality, whereas lexical stimuli are the weakest. Meta-analyses independent of studies using Regions of Interest (ROI) revealed no biasing effect Core neuronal arousal in the brain, which may be at first independent of conscious processing, potentially involves a network incorporating primary visual areas, somatosensory, implicit memory and conflict monitoring regions. These data could provide candidate brain regions for the study of psychiatric disorders associated with aberrant automatic emotional processing.
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23.
  • Brooks, Samantha J., et al. (författare)
  • Important gender differences in psychosomatic and school-related complaints in relation to adolescent weight status
  • 2021
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Underweight or overweight in adolescence is linked to several adverse health outcomes. Less evidence exists about the association between weight status and school-related psychosocial characteristics in high income countries. We sought to investigate the relationship between weight status and psychosomatic and school-related complaints with a focus on gender differences. The study is a cohort of 18,462 adolescents (12-19 years; 51% girls) conducted in Sweden. The associations between weight status and psychosomatic and school-related complaints were estimated by binary logistic regression adjusted for several potential confounders. After correction for multiple testing, being underweight or overweight/obese was adversely associated with several psychosomatic and school-related complaints with significant differences between boys and girls. Specifically, underweight boys had higher odds to have psychosomatic complaints than normal-weight boys, while no such associations were observed among underweight girls. Overweight/obese (vs. normal-weight) boys had higher odds to complain about headache, pain in the back/hips, and feeling low. Overweight/obese (vs. normal-weight) girls were more likely to complain about feeling low, anxious/worried and having difficulty in falling asleep (P <= 0.01). In relation to school-related complaints (e.g., being bullied at school and academic failure), greater associations were observed for overweight/obese girls and boys than for underweight adolescents compared with normal-weight peers.
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24.
  • Brooks, Samantha J, et al. (författare)
  • Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity : a meta-analysis of fMRI studies.
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4, s. e60393-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND OBJECTIVES: Obesity is emerging as the most significant health concern of the twenty-first century. A wealth of neuroimaging data suggest that weight gain might be related to aberrant brain function, particularly in prefrontal cortical regions modulating mesolimbic addictive responses to food. Nevertheless, food addiction is currently a model hotly debated. Here, we conduct a meta-analysis of neuroimaging data, examining the most common functional differences between normal-weight and obese participants in response to food stimuli.DATA SOURCE: We conducted a search using several journal databases and adhered to the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses' (PRISMA) method. To this aim, 10 studies were found with a total of 126 obese participants, 129 healthy controls, equaling 184 foci (146 increased, 38 decreased activation) using the Activation Likelihood Estimation (ALE) technique. Out of the 10 studies, 7 investigated neural responses to food versus non-food images.RESULTS: In response to food images, obese in comparison to healthy weight subjects had increased activation in the left dorsomedial prefrontal cortex, right parahippocampal gyrus, right precentral gyrus and right anterior cingulate cortex, and reduced activation in the left dorsolateral prefrontal cortex and left insular cortex.CONCLUSIONS: Prefrontal cortex areas linked to cognitive evaluation processes, such as evaluation of rewarding stimuli, as well as explicit memory regions, appear most consistently activated in response to images of food in those who are obese. Conversely, a reduced activation in brain regions associated with cognitive control and interoceptive awareness of sensations in the body might indicate a weakened control system, combined with hypo-sensitivity to satiety and discomfort signals after eating in those who are prone to overeat.
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25.
  • Brooks, Samantha J, et al. (författare)
  • Obsessive-compulsivity and working memory are associated with differential prefrontal cortex and insula activation in adolescents with a recent diagnosis of an eating disorder
  • 2014
  • Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123 .- 0925-4927. ; 224:3, s. 246-253
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of rumination at the beginning of eating disorder (ED) is not well understood. We hypothesised that impulsivity, rumination and restriction could be associated with neural activity in response to food stimuli in young individuals with eating disorders (ED). We measured neural responses with functional magnetic resonance imaging (fMRI), tested working memory (WM) and administered the eating disorders examination questionnaire (EDE-Q), Barratt impulsivity scale (BIS-11) and obsessive-compulsive inventory (OCI-R) in 15 adolescent females with eating disorder not otherwise specified (EDNOS) (mean age 15 years) and 20 age-matched healthy control females. We found that EDNOS subjects had significantly higher scores on the BIS 11, EDE-Q and OCI-R scales. Significantly increased neural responses to food images in the EDNOS group were observed in the prefrontal circuitry. OCI-R scores in the EDNOS group also significantly correlated with activity in the prefrontal circuitry and the cerebellum. Significantly slower WM responses negatively correlated with bilateral superior frontal gyrus activity in the EDNOS group. We conclude that ruminations, linked to WM, are present in adolescent females newly diagnosed with EDNOS. These may be risk factors for the development of an eating disorder and may be detectable before disease onset.
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26.
  • Brooks, Samantha J., et al. (författare)
  • Review of the Neural Processes of Working Memory Training : Controlling the Impulse to Throw the Baby Out With the Bathwater
  • 2020
  • Ingår i: Frontiers in Psychiatry. - : FRONTIERS MEDIA SA. - 1664-0640. ; 11
  • Forskningsöversikt (refereegranskat)abstract
    • Background Smartphone technology has enabled the creation of many working memory training (WMT) Apps, with those peer-reviewed described in a recent review. WMT claims to improve working memory, attention deficits, hyperactivity and fluid intelligence, in line with plasticity brain changes. Critics argue that WMT is unable to achieve "far-transfer"-the attainment of benefits to cognition from one taught context to another dissimilar context-associated with improved quality of life. However, brain changes after a course of WMT in frontoparietal and striatal circuits-that often occur prior to behavioral changes-may be a better indicator of far-transfer efficacy, especially to improve impulse control commonly dysregulated in those with addictive disorders, yet not commonly examined in WMT studies. Method In contrast to previous reviews, the aim here is to focus on the findings of brain imaging WMT training studies across various imaging modalities that use various paradigms, publishedviaPubMed, Scopus, Medline, and Google Scholar. Results 35 brain imaging studies utilized fMRI, structural imaging (MRI, DTI), functional connectivity, EEG, transcranial direct current stimulation (tDCS), cerebral perfusion, and neurogenetic analyses with tasks based on visuospatial and auditory working memory, dual and standard n-back. Discussion Evidence suggests that repeated WMT reduces brain activation in frontoparietal and striatal networks reflective of increased neural circuitry efficiencyviamyelination and functional connectivity changes. Neural effects of WMT may persist months after training has ended, lead to non-trained task transfer, be strengthened by auxiliary methods such as tDCS and be related to COMT polymorphisms. WMT could be utilized as an effective, non-invasive intervention for working memory deficits to treat impulse and affective control problems in people with addictive disorders.
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27.
  • Brooks, Samantha J., et al. (författare)
  • Self-Reported Psychosomatic Complaints and Conduct Problems in Swedish Adolescents
  • 2022
  • Ingår i: Children. - : MDPI AG. - 2227-9067. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Physical conditions in children and adolescents are often under reported during mainstream school years and may underlie mental health disorders. Additionally, comparisons between younger and older schoolchildren may shed light on developmental differences regarding the way in which physical conditions translate into conduct problems. The aim of the current study was to examine the incidence of psychosomatic complaints (PSC) in young and older adolescent boys and girls who also report conduct problems. A total of 3132 Swedish adolescents (age range 15-18 years, 47% boys) completed the Uppsala Life and Health Cross-Sectional Survey (LHS) at school. The LHS question scores were categorised by two researchers who independently identified questions that aligned with DSM-5 conduct disorder (CD) criteria and PSC. MANOVA assessed the effects of PSC, age, and gender on scores that aligned with the DSM criteria for CD. The main effects of gender, age, and PSC on the conduct problem scores were observed. Adolescents with higher PSC scores had higher conduct problem scores. Boys had higher serious violation of rules scores than girls, particularly older boys with higher PSC scores. Psychosomatic complaints could be a useful objective identifier for children and adolescents at risk of developing conduct disorders. This may be especially relevant when a reliance on a child's self-reporting of their behavior may not help to prevent a long-term disturbance to their quality of life.
  •  
28.
  • Brooks, Samantha J., et al. (författare)
  • Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa
  • 2012
  • Ingår i: Consciousness and Cognition. - : Elsevier BV. - 1053-8100 .- 1090-2376. ; 21:2, s. 751-763
  • Tidskriftsartikel (refereegranskat)abstract
    • Prefrontal cortex (PFC) is dysregulated in women with restricting anorexia nervosa (RAN). It is not known whether appetitive non-conscious stimuli bias cognitive responses in those with RAN. Thirteen women with RAN and 20 healthy controls (HC) completed a dorsolateral PFC (DLPFC) working memory task and an anterior cingulate cortex (ACC) conflict task, while masked subliminal food, aversive and neutral images were presented. During the DLPFC task, accuracy was higher in the RAN compared to the HC group, but superior performance was compromised when subliminal food stimuli were presented: errors positively correlated with self-reported trait anxiety in the RAN group. These effects were not observed in the ACC task. Appetitive activation is intact and anxiogenic in women with RAN, and non-consciously interacts with working memory processes associated with the DLPFC. This interaction mechanism may underlie cognitive inhibition of appetitive processes that are anxiety inducing, in people with AN.
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29.
  • Brooks, Samantha J., et al. (författare)
  • The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder
  • 2017
  • Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 8
  • Forskningsöversikt (refereegranskat)abstract
    • Prefrontal cortex executive functions, such as working memory (WM) interact with limbic processes to foster impulse control. Such an interaction is referred to in a growing body of publications by terms such as cognitive control, cognitive inhibition, affect regulation, self-regulation, top-down control, and cognitive–emotion interaction. The rising trend of research into cognitive control of impulsivity, using various related terms reflects the importance of research into impulse control, as failure to employ cognitions optimally may eventually result in mental disorder. Against this background, we take a novel approach using an impulse control spectrum model – where anorexia nervosa (AN) and substance use disorder (SUD) are at opposite extremes – to examine the role of WM for cognitive control. With this aim, we first summarize WM processes in the healthy brain in order to frame a systematic review of the neuropsychological, neural and genetic findings of AN and SUD. In our systematic review of WM/cognitive control, we found n = 15 studies of AN with a total of n = 582 AN and n = 365 HC participants; and n = 93 studies of SUD with n = 9106 SUD and n = 3028 HC participants. In particular, we consider how WM load/capacity may support the neural process of excessive epistemic foraging (cognitive sampling of the environment to test predictions about the world) in AN that reduces distraction from salient stimuli. We also consider the link between WM and cognitive control in people with SUD who are prone to ‘jumping to conclusions’ and reduced epistemic foraging. Finally, in light of our review, we consider WM training as a novel research tool and an adjunct to enhance treatment that improves cognitive control of impulsivity.
  •  
30.
  • Brooks, Samantha J., et al. (författare)
  • Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa : An fMRI Study
  • 2012
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3, s. e34000-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women with anorexia nervosa (AN) have aberrant cognitions about food and altered activity in prefrontal cortical and somatosensory regions to food images. However, differential effects on the brain when thinking about eating food between healthy women and those with AN is unknown. Methods: Functional magnetic resonance imaging (fMRI) examined neural activation when 42 women thought about eating the food shown in images: 18 with AN (11 RAN, 7 BPAN) and 24 age-matched controls (HC). Results: Group contrasts between HC and AN revealed reduced activation in AN in the bilateral cerebellar vermis, and increased activation in the right visual cortex. Preliminary comparisons between AN subtypes and healthy controls suggest differences in cortical and limbic regions. Conclusions: These preliminary data suggest that thinking about eating food shown in images increases visual and prefrontal cortical neural responses in females with AN, which may underlie cognitive biases towards food stimuli and ruminations about controlling food intake. Future studies are needed to explicitly test how thinking about eating activates restraint cognitions, specifically in those with restricting vs. binge-purging AN subtypes.
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31.
  • Brooks, Samantha, et al. (författare)
  • Using the research domain criteria (RDoC) to conceptualize impulsivity and compulsivity in relation to addiction
  • 2017
  • Ingår i: Brain Research In Addiction. - : ELSEVIER. - 9780128135013 ; , s. 177-218
  • Bokkapitel (refereegranskat)abstract
    • Nomenclature for mental disorder was updated in 2013 with the publication of the fifth edition of the Diagnostic and Statistical Manual (DSM-5). In DSM-5, substance use disorders are framed as more dimensional. First, the distinction between abuse and dependence is replaced by substance use. Second, the addictions section now covers both substances and behavioral addictions. This contemporary move toward dimensionality and transdiagnosis in the addictions and other disorders embrace accumulating cognitive-affective neurobiological evidence that is reflected in the United States' National Institutes of Health Research Domain Criteria (NIH RDoC). TheRDoCcalls for the further development of transdiagnostic approaches to psychopathy and includes five domains to improve research. Additionally, the RDoC suggests that these domains can be measured in terms of specific units of analysis. In line with these suggestions, recent publications have stimulated updated neurobiological conceptualizations of two transdiagnostic concepts, namely impulsivity and compulsivity and their interactions that are applicable to addictive disorders. However, there has not yet been a review to examine the constructs of impulsivity and compulsivity in relation to addiction in light of the research-oriented RDoC. By doing so it may become clearer as to whether impulsivity and compulsivity function antagonistically, complementarily or in some other way at the behavioral, cognitive, and neural level and how this relationship underpins addiction. Thus, here we consider research into impulsivity and compulsivity in light of the transdiagnostic RDoC to help better understand these concepts and their application to evidence-based clinical intervention for addiction.
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32.
  • Dahlén, Amelia, et al. (författare)
  • Subliminal Emotional Faces Elicit Predominantly Right-Lateralized Amygdala Activation : A Systematic Meta-Analysis of fMRI Studies
  • 2022
  • Ingår i: Frontiers in Neuroscience. - : Frontiers Media S.A.. - 1662-4548 .- 1662-453X. ; 16
  • Forskningsöversikt (refereegranskat)abstract
    • Prior research suggests that conscious face processing occurs preferentially in right hemisphere occipito-parietal regions. However, less is known about brain regions associated with non-conscious processing of faces, and whether a right-hemispheric dominance persists in line with specific affective responses. We aim to review the neural responses systematically, quantitatively, and qualitatively underlying subliminal face processing. PubMed was searched for Functional Magnetic Resonance Imaging (fMRI) publications assessing subliminal emotional face stimuli up to March 2022. Activation Likelihood Estimation (ALE) meta-analyses and narrative reviews were conducted on all studies that met ALE requirements. Risk of bias was assessed using the AXIS tool. In a meta-analysis of all 22 eligible studies (merging clinical and non-clinical populations, whole brain and region of interest analyses), bilateral amygdala activation was reported in the left (x = -19.2, y = 1.5, z = -17.1) in 59% of studies, and in the right (x = 24.4, y = -1.7, z = -17.4) in 68% of studies. In a second meta-analysis of non-clinical participants only (n = 18), bilateral amygdala was again reported in the left (x = -18, y = 3.9, z = -18.4) and right (x = 22.8, y = -0.9, z = -17.4) in 56% of studies for both clusters. In a final meta-analysis of whole-brain studies only (n=14), bilateral amygdala was also reported in the left (x = -20.2, y = 2.9, z = -17.2) in 64% of studies, and right (x = 24.2, y = -0.7, z = -17.8) in 71% of studies. The findings suggest that non-consciously detected emotional faces may influence amygdala activation, especially right-lateralized (a higher percentage of convergence in studies), which are integral for pre-conscious affect and long-term memory processing.
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33.
  • de Jorge Martínez, Clara, et al. (författare)
  • Genetics of anorexia nervosa : An overview of genome-wide association studies and emerging biological links
  • 2022
  • Ingår i: Journal of genetics and genomics = Yi chuan xue bao. - : Elsevier. - 1673-8527. ; 49:1, s. 1-12
  • Forskningsöversikt (refereegranskat)abstract
    • Anorexia nervosa (AN) is a complex disorder with a strong genetic component. Comorbidities are frequent and there is substantial overlap with other disorders. The lack of understanding of the molecular and neuroanatomical causes has made it difficult to develop effective treatments and it is often difficult to treat in clinical practice. Recent advances in genetics have changed our understanding of polygenic diseases, increasing the possibility of understanding better how molecular pathways are intertwined. This review synthetizes the current state of genetic research providing an overview of genome-wide association studies (GWAS) findings in AN as well as overlap with other disorders, traits, pathways, and imaging results. This paper also discusses the different putative global pathways that are contributing to the disease including the evidence for metabolic and psychiatric origin of the disease.
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34.
  • Gaudio, Santino, et al. (författare)
  • A systematic review of resting-state functional-MRI studies in anorexia nervosa : Evidence for functional connectivity impairment in cognitive control and visuospatial and body-signal integration
  • 2016
  • Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 71, s. 578-589
  • Forskningsöversikt (refereegranskat)abstract
    • This paper systematically reviews the literature pertaining to the use of resting-state functional magnetic resonance imaging (rsfMRI) in anorexia nervosa (AN), classifying studies on the basis of different analysis approaches. We followed PRISMA guidelines. Fifteen papers were included, investigating a total of 294 participants with current or past AN and 285 controls. The studies used seed-based, whole-brain independent component analysis (ICA), network-of-interest ICA based and graph analysis approaches. The studies showed relatively consistent overlap in results, yet little overlap in their analytical approach and/or a-priori assumptions. Functional connectivity alterations were mainly found in the corticolimbic circuitry, involved in cognitive control and visual and homeostatic integration. Some overlapping findings were found in brain areas putatively important in AN, such as the insula. These results suggest altered functional connectivity in networks/areas linked to the main symptom domains of AN, such as impaired cognitive control and body image disturbances. These preliminary evidences suggest that more targeted treatments need to be developed that focus on these two symptom domains. Further studies with multi-approach analyses and longitudinal designs are needed to better understand the complexity of AN.
  •  
35.
  • Meneguzzo, Paolo, et al. (författare)
  • Subliminal versus supraliminal stimuli activate neural responses in anterior cingulate cortex, fusiform gyrus and insula : a meta-analysis of fMRI studies
  • 2014
  • Ingår i: BMC Psychology. - : Springer Science and Business Media LLC. - 2050-7283. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDNon-conscious neural activation may underlie various psychological functions in health and disorder. However, the neural substrates of non-conscious processing have not been entirely elucidated. Examining the differential effects of arousing stimuli that are consciously, versus unconsciously perceived will improve our knowledge of neural circuitry involved in non-conscious perception. Here we conduct preliminary analyses of neural activation in studies that have used both subliminal and supraliminal presentation of the same stimulus.METHODSWe use Activation Likelihood Estimation (ALE) to examine functional Magnetic Resonance Imaging (fMRI) studies that uniquely present the same stimuli subliminally and supraliminally to healthy participants during functional magnetic resonance imaging (fMRI). We included a total of 193 foci from 9 studies representing subliminal stimulation and 315 foci from 10 studies representing supraliminal stimulation.RESULTSThe anterior cingulate cortex is significantly activated during both subliminal and supraliminal stimulus presentation. Subliminal stimuli are linked to significantly increased activation in the right fusiform gyrus and right insula. Supraliminal stimuli show significantly increased activation in the left rostral anterior cingulate.CONCLUSIONSNon-conscious processing of arousing stimuli may involve primary visual areas and may also recruit the insula, a brain area involved in eventual interoceptive awareness. The anterior cingulate is perhaps a key brain region for the integration of conscious and non-conscious processing. These preliminary data provide candidate brain regions for further study in to the neural correlates of conscious experience.
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36.
  • Nordenskjöld, Richard, et al. (författare)
  • Intracranial volume estimated with commonly used methods could introduce bias in studies including brain volume measurements
  • 2013
  • Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 83, s. 355-360
  • Tidskriftsartikel (refereegranskat)abstract
    • In brain volumetric studies, intracranial volume (ICV) is often used as an estimate of pre-morbid brain size as well as to compensate for inter-subject variations in head size. However, if the estimated ICV is biased by for example gender or atrophy, it could introduce errors in study results. To evaluate how two commonly used methods for ICV estimation perform, computer assisted reference segmentations were created and evaluated. Segmentations were created for 399 MRI volumes from 75-year-old subjects, with 53 of these subjects having an additional scan and segmentation created at age 80. ICV estimates from Statistical Parametric Mapping (SPM, version 8) and Freesurfer (FS, version 5.1.0) were compared to the reference segmentations, and bias related to skull size (approximated with the segmentation measure), gender or atrophy were tested for. The possible ICV related effect on associations between normalized hippocampal volume and factors gender, education and cognition was evaluated by normalizing hippocampal volume with different ICV measures. Excellent agreement was seen for inter- (r=0.999) and intra- (r=0.999) operator reference segmentations. Both SPM and FS overestimated ICV. SPM showed bias associated with gender and atrophy while FS showed bias dependent on skull size. All methods showed good correlation between time points in the longitudinal data (reference: 0.998, SPM: 0.962, FS: 0.995). Hippocampal volume showed different associations with cognition and gender depending on which ICV measure was used for hippocampal volume normalization. These results show that the choice of method used for ICV estimation can bias results in studies including brain volume measurements.
  •  
37.
  • Olivo, Gaia, et al. (författare)
  • Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.
  • 2018
  • Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 51:1, s. 39-45
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients.METHOD: We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated.RESULTS: Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups.DISCUSSION: The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN.
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38.
  •  
39.
  • Olivo, Gaia, et al. (författare)
  • Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior : A longitudinal DTI study in adolescents with restrictive eating disorders
  • 2017
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Few studies have used diffusion tensor imaging (DTI) to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED), and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs) through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA) and mean, radial and axial diffusivities (MD, RD and AD, respectively). Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.
  •  
40.
  • Olivo, Gaia, et al. (författare)
  • Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa
  • 2019
  • Ingår i: International Journal of Eating Disorders. - : Wiley. - 0276-3478 .- 1098-108X. ; 52:2, s. 166-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with atypical anorexia nervosa (AN) are often in the normal-weight range at presentation; however, signs of starvation and medical instability are not rare. White matter (WM) microstructural correlates of atypical AN have not yet been investigated, leaving an important gap in our knowledge regarding the neural pathogenesis of this disorder.Method: We investigated WM microstructural integrity in 25 drug-naive adolescent patients with atypical AN and 25 healthy controls, using diffusion tensor imaging (DTI) with a tract-based spatial statistics (TBSS) approach. Psychological variables related to the eating disorder and depressive symptoms were also evaluated by administering the eating disorder examination questionnaire (EDE-Q) and the Montgomery-angstrom sberg depression rating scale (MADRS-S) respectively, to all participants.Results: Patients and controls were in the normal-weight range and did not differ from the body mass index standard deviations for their age. No between groups difference in WM microstructure could be detected.Discussion: Our findings support the hypothesis that brain structural alterations may not be associated to early-stage atypical AN. These findings also suggest that previous observations of alterations in WM microstructure in full syndrome AN may constitute state-related consequences of severe weight loss. Whether the preservation of WM structure is a pathogenetically discriminant feature of atypical AN or only an effect of a less severe nutritional disturbance, will have to be verified by future studies on larger samples, possibly directly comparing AN and atypical AN.
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41.
  • Olivo, Gaia, et al. (författare)
  • Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa
  • 2018
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Atypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naive adolescent patients with atypical AN, and 24 healthy controls. Psychological traits related to the ED and depressive symptoms have been assessed using the Eating Disorders Examination Questionnaire (EDE-Q) and the Montgomery-Asberg Depression Rating Scale self-reported (MADRS-S) respectively. Reduced connectivity was found in patients in brain areas involved in face-processing and social cognition, such as the left putamen, the left occipital fusiform gyrus, and specific cerebellar lobules. The connectivity was, on the other hand, increased in patients compared with controls from the right inferior temporal gyrus to the superior parietal lobule and superior lateral occipital cortex. These areas are involved in multimodal stimuli integration, social rejection and anxiety. Patients scored higher on the EDE-Q and MADRS-S questionnaires, and the MADRS-S correlated with connectivity from the right inferior temporal gyrus to the superior parietal lobule in patients. Our findings point toward a role for an altered development of socio-emotional skills in the pathogenesis of atypical AN. Nonetheless, longitudinal studies will be needed to assess whether these connectivity alterations might be a neural marker of the pathology.
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42.
  • Olivo, Gaia, et al. (författare)
  • Resting-State Bra in and the FTO Obesity Risk Allele : Default Mode, Sensorimotor, and Salience Network Connectivity Underlying Different Somatosensory Integration and Reward Processing between Genotypes
  • 2016
  • Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene are linked to obesity, but how these SNPs influence resting-state neural activation is unknown. Few brain-imaging studies have investigated the influence of obesity-related SNPs on neural activity, and no study has investigated resting-state connectivity patterns. We tested connectivity within three, main resting-state networks: default mode (DMN), sensorimotor (SMN), and salience network (SN) in 30 male participants, grouped based on genotype for the rs9939609 FTO SNP, as well as punishment and reward sensitivity measured by the Behavioral Inhibition (BIS) and Behavioral Activation System (BAS) questionnaires. Because obesity is associated with anomalies in both systems, we calculated a BIS/BAS ratio (BBr) accounting for features of both scores. A prominence of BIS over BAS (higher BBr) resulted in increased connectivity in frontal and paralimbic regions. These alterations were more evident in the obesity-associated AA genotype, where a high BBr was also associated with increased SN connectivity in dopaminergic circuitries, and in a subnetwork involved in somatosensory integration regarding food. Participants with AA genotype and high BBr, compared to corresponding participants in the TT genotype, also showed greater DMN connectivity in regions involved in the processing of food cues, and in the SMN for regions involved in visceral perception and reward-based learning. These findings suggest that neural connectivity patterns influence the sensitivity toward punishment and reward more closely in the AA carriers, predisposing them to developing obesity. Our work explains a complex interaction between genetics, neural patterns, and behavioral measures in determining the risk for obesity and may help develop individually-tailored strategies for obesity prevention.
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43.
  • Schiöth, Helgi B., et al. (författare)
  • Brain Insulin Signaling and Alzheimer's Disease : Current Evidence and Future Directions
  • 2012
  • Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 46:1, s. 4-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin receptors in the brain are found in high densities in the hippocampus, a region that is fundamentally involved in the acquisition, consolidation, and recollection of new information. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of experiments involving healthy humans has shown that increased central nervous system (CNS) insulin action enhances learning and memory processes associated with the hippocampus. Since Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes and attenuated permeation of blood-borne insulin across the blood-brain barrier, impaired brain insulin signaling could partially account for the cognitive deficits associated with this disease. Considering that insulin mitigates hippocampal synapse vulnerability to amyloid beta and inhibits the phosphorylation of tau, pharmacological strategies bolstering brain insulin signaling, such as intranasal insulin, could have significant therapeutic potential to deter AD pathogenesis.
  •  
44.
  • Schiöth, Helgi B., et al. (författare)
  • Insulin to treat Alzheimer's disease : just follow your nose?
  • 2012
  • Ingår i: Expert Review of Clinical Pharmacology. - : Informa UK Limited. - 1751-2433 .- 1751-2441. ; 5:1, s. 17-20
  • Forskningsöversikt (refereegranskat)abstract
    • Alzheimer's disease (AD) is linked to CNS insulin resistance, decreased expression of insulin and insulin receptor genes, and lower cerebrospinal insulin levels. Against this background, impaired brain insulin signaling may account for some of the cognitive deficits associated with this disease. Using the intranasal method, which effectively bypasses the blood-brain barrier to deliver and target insulin directly from the nose to the brain, a series of acute clinical trials involving healthy humans and AD patients have shown that increased CNS insulin action enhances learning and memory processes. This article summarizes and evaluates data from a recently published clinical trial, in which 4 months of intranasal insulin administration (20 IU insulin/day) preserved not only general cognition but also reduced the loss of metabolic integrity of the brain in adults with mild-to-moderate AD.
  •  
45.
  • Suda, Masashi, et al. (författare)
  • Provocation of Symmetry/Ordering Symptoms in Anorexia nervosa : A Functional Neuroimaging Study
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Anorexia nervosa (AN), obsessive-compulsive disorder (OCD), and obsessive-compulsive personality disorder (OCPD) are often co-morbid; however, the aetiology of such co-morbidity has not been well investigated. This study examined brain activation in women with AN and in healthy control (HC) women during the provocation of symmetry/ordering-related anxiety. During provocation, patients with AN showed more anxiety compared to HCs, which was correlated with the severity of symmetry/ordering symptoms. Activation in the right parietal lobe and right prefrontal cortex (rPFC) in response to provocation was reduced in the AN group compared with the HC group. The reduced right parietal activation observed in the AN group is consistent with parietal lobe involvement in visuospatial cognition and with studies of OCD reporting an association between structural abnormalities in this region and the severity of 'ordering' symptoms. Reduced rPFC activation in response to symmetry/ordering provocation has similarities with some, but not all, data collected from patients with AN who were exposed to images of food and bodies. Furthermore, the combination of data from the AN and HC groups showed that rPFC activation during symptom provocation was inversely correlated with the severity of symmetry/ordering symptoms. These data suggest that individuals with AN have a diminished ability to cognitively deal with illness-associated symptoms of provocation. Furthermore, our data also suggest that symptom provocation can progressively overload attempts by the rPFC to exert cognitive control. These findings are discussed in the context of the current neurobiological models of AN.
  •  
46.
  • Titova, Olga E, et al. (författare)
  • Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions : a meta-analysis of VBM studies
  • 2013
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 13:1, s. 110-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDStructural imaging studies demonstrate brain tissue abnormalities in eating disorders, yet a quantitative analysis has not been done.METHODSIn global and regional meta-analyses of 9 voxel-based morphometry (VBM) studies, with a total of 228 eating disorder participants (currently ill with anorexia nervosa), and 240 age-matched healthy controls, we compare brain volumes using global and regional analyses.RESULTSAnorexia nervosa (AN) patients have global reductions in gray (effect size = -0.66) and white matter (effect size = -0.74) and increased cerebrospinal fluid (effect size = 0.98) and have regional decreases in left hypothalamus, left inferior parietal lobe, right lentiform nucleus and right caudate, and no significant increases. No significant difference in hemispheric lateralization was found.CONCLUSIONSGlobal and regional meta-analyses suggest that excessive restrained eating as found in those with anorexia nervosa coincides with structural brain changes analogous to clinical symptoms.
  •  
47.
  • Titova, Olga E, et al. (författare)
  • Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly
  • 2013
  • Ingår i: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 35:4, s. 1495-1505
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, we tested whether elderly with a high dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) would have higher cognitive test scores and greater brain volume than those with low dietary intake of these fatty acids. Data were obtained from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. The dietary intake of EPA and DHA was determined by a 7-day food protocol in 252 cognitively healthy elderly (122 females) at the age of 70 years. At age 75, participants' global cognitive function was examined, and their brain volumes were measured by magnetic resonance imaging (MRI). Three different multivariate linear regression models were applied to test our hypothesis: model A (adjusted for gender and age), model B (additionally controlled for lifestyle factors, e.g., education), and model C (further controlled for cardiometabolic factors, e.g., systolic blood pressure). We found that the self-reported 7-day dietary intake of EPA and DHA at the age of 70 years was positively associated with global gray matter volume (P < 0.05, except for model C) and increased global cognitive performance score (P < 0.05). However, no significant associations were observed between the dietary intake of EPA and DHA and global white matter, total brain volume, and regional gray matter, respectively. Further, no effects were observed when examining cognitively impaired (n = 27) elderly as separate analyses. These cross-sectional findings suggest that dietary intake of EPA and DHA may be linked to improved cognitive health in late life but must be confirmed in patient studies.
  •  
48.
  • Titova, Olga E, et al. (författare)
  • Mediterranean diet habits in older individuals : Associations with cognitive functioning and brain volumes
  • 2013
  • Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:12, s. 1443-1448
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine the association between dietary habits, cognitive functioning and brain volumes in older individuals, data from 194 cognitively healthy individuals who participated in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort were used. At age 70, participants kept diaries of their food intake for 1week. These records were used to calculate a Mediterranean diet (MeDi) score (comprising dietary habits traditionally found in Mediterranean countries, e.g. high intake of fruits and low intake of meat), with higher scores indicating more pronounced MeDi-like dietary habits. Five years later, participants' cognitive capabilities were examined by the seven minute screening (7MS) (a cognitive test battery used by clinicians to screen for dementia), and their brain volumes were measured by volumetric magnetic resonance imaging. Multivariate linear regression analyses were constructed to examine the association between the total MeDi score and cognitive functioning and brain volumes. In addition, possible associations between MeDi's eight dietary features and cognitive functioning and brain volumes were investigated. From the eight dietary features included in the MeDi score, pertaining to a low consumption of meat and meat products was linked to a better performance on the 7MS test (P=0.001) and greater total brain volume (P=0.03), i.e. the sum of white and gray matter. Integrating all dietary features of MeDi into score did not explain additional variance. These observational findings suggest that keeping to a low meat intake could prove to be an impact-driven public health policy to support healthy cognitive aging, when confirmed by longitudinal studies. Further, they suggest that the MeDi score is a construct that may mask possible associations of single MeDi features with brain health domains in elderly populations.
  •  
49.
  • Titova, Olga E., et al. (författare)
  • The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices
  • 2012
  • Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 108:8, s. 1341-1345
  • Tidskriftsartikel (refereegranskat)abstract
    • Smoking during pregnancy has been shown to be detrimental for the developing fetus. The effects of active and passive maternal smoking on umbilical cord serum levels of vitamin A and vitamin E were examined. Secondary measures included anthropometric parameters in the newborn. Maternal and umbilical cord serum levels of vitamins A and E were measured at delivery. The mothers were assigned to three groups: non-smoking (n 12); passive smoking (n 13); active smoking (n 18). Based on multivariate linear regressions, active smoking during pregnancy was associated with increased umbilical cord serum levels of vitamin A and vitamin E. While enhanced circulating levels of vitamin A in cord blood were also found in non-smoking mothers exposed to tobacco smoke during pregnancy, those of vitamin E were not influenced. Further, an inverse association between smoking behaviour during pregnancy and birth length was observed, with shortest length in active smokers followed by passive smoking mothers. Active and passive maternal smoking behaviour during pregnancy increases the fetal demand for antioxidant compounds in order to counteract the oxidative burden by cigarette smoke. Against this background, the observed increase in umbilical cord serum levels of vitamins A and E may subserve antioxidative processes in response to tobacco smoke-induced oxidative stress. This would reduce the availability of vitamins A and E for fetal maturation, which is critical inasmuch as both compounds are indispensable for the developing fetus. However, due to the cross-sectional nature of our observation, this line of reasoning definitely requires validation in cause-effect experiments in the future.
  •  
50.
  • Tully, Jamie L., et al. (författare)
  • Ketamine treatment for refractory anxiety : A systematic review
  • 2022
  • Ingår i: British Journal of Clinical Pharmacology. - : John Wiley & Sons. - 0306-5251 .- 1365-2125. ; 88:10, s. 4412-4426
  • Forskningsöversikt (refereegranskat)abstract
    • There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective. Ketamine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) glutamate receptor, which underlies its induction of pain relief and anaesthesia. However, the role of NMDA receptors in anxiety reduction is still relatively unknown. To fill this paucity in the literature, this systematic review assesses the evidence that ketamine significantly reduces refractory anxiety and discusses to what extent this may be mediated by NMDA receptor antagonism and other receptors. We highlight the temporary nature of the anxiolytic effects and discuss the high discrepancy among the study designs regarding many fundamental factors such as administration routes, complementary treatments and other treatments.
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