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  • 1.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, Matthew J
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Craft, Suzanne
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 3, p. 488-494Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE

    Impaired 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 METHODS

    Insulin 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).

    RESULTS

    The 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.

    CONCLUSIONS

    These 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.

  • 2.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Burgos, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Le Grevès, Madeleine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Association between physical activity and brain health in older adults2013In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 34, no 1, p. 83-90Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rönnemaa, Elina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sällman Almén, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schultes, Bernd
    Interdisciplinary Obesity Center, Kantonsspital St. Gallen.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    The fat mass and obesity gene is linked to reduced verbal fluency in overweight and obese elderly men2011In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 32, no 6, p. 1159.e1-1159.e5Article in journal (Refereed)
    Abstract [en]

    Humans carrying the prevalent rs9939609 A allele of the fat mass and obesity-associated (FTO) gene are more susceptible to developing obesity than noncarries. Recently, polymorphisms in the FTO gene of elderly subjects have also been linked to a reduced volume in the frontal lobe as well as increased risk for incident Alzheimer disease. However, so far there is no evidence directly linking the FTO gene to functional cognitive processes. Here we examined whether the FTO rs9939609 A allele is associated with verbal fluency performance in 355 elderly men at the age of 82 years who have no clinically apparent cognitive impairment. Retrieval of verbal memory is a good surrogate measure reflecting frontal lobe functioning. Here we found that obese and overweight but not normal weight FTO A allele carriers showed a lower performance on verbal fluency than non-carriers (homozygous for rs9939609 T allele). This effect was not observed for a measure of general cognitive performance (i.e., Mini-Mental State Examination score), thereby indicating that the FTO gene primarily affects frontal lobe-dependent cognitive processes in elderly men.

  • 4.
    Benedict, Christian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Shostak, Anton
    Lange, Tanja
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schultes, Bernd
    Born, Jan
    Oster, Henrik
    Hallschmid, Manfred
    Diurnal Rhythm of Circulating Nicotinamide Phosphoribosyltransferase (Nampt/Visfatin/PBEF): Impact of Sleep Loss and Relation to Glucose Metabolism2012In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 97, no 2, p. E218-E222Article in journal (Refereed)
    Abstract [en]

    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.

    Intervention

    Fourteen 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).

    Conclusions

    Serum 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.

  • 5.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Barker, Gareth J
    O'Daly, Owen G
    Brammer, Michael
    Williams, Steven Cr
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Treasure, Janet
    Campbell, Iain C
    Restraint of appetite and reduced regional brain volumes in anorexia nervosa: a voxel-based morphometric study2011In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 11, p. 179-Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Burgos, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kempton, M J
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nordenskjöld, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Nylander, Ruta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study2013In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 37, no 2, p. 230-236Article in journal (Refereed)
    Abstract [en]

    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.

  • 7.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity: a meta-analysis of fMRI studies.2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, p. e60393-Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Brooks, Samantha J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Funk, Sabina G
    Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
    Young, Susanne Y
    Department of Psychiatry, Stellenbosch University, Bellville, South Africa.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    The Role of Working Memory for Cognitive Control in Anorexia Nervosa versus Substance Use Disorder2017In: Frontiers in Psychology, ISSN 1664-1078, E-ISSN 1664-1078, Vol. 8, article id 1651Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 9.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Nilsson, Emil K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stein, Dan J
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    BDNF polymorphisms are linked to poorer working memory performance, reduced cerebellar and hippocampal volumes and differences in prefrontal cortex in a Swedish elderly population2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 1, p. e82707-Article in journal (Refereed)
    Abstract [en]

    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.

  • 10.
    Brooks, Samantha J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    O'Daly, Owen G.
    Uher, Rudolf
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Treasure, Janet
    Campbell, Iain C.
    Subliminal food images compromise superior working memory performance in women with restricting anorexia nervosa2012In: Consciousness and Cognition, ISSN 1053-8100, E-ISSN 1090-2376, Vol. 21, no 2, p. 751-763Article in journal (Refereed)
    Abstract [en]

    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.

  • 11.
    Brooks, Samantha J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    O'Daly, Owen
    Uher, Rudolf
    Friederich, Hans-Christoph
    Giampietro, Vincent
    Brammer, Michael
    Williams, Steven C. R.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Treasure, Janet
    Campbell, Iain C.
    Thinking about Eating Food Activates Visual Cortex with Reduced Bilateral Cerebellar Activation in Females with Anorexia Nervosa: An fMRI Study2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3, p. e34000-Article in journal (Refereed)
    Abstract [en]

    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.

  • 12.
    Brooks, Samantha J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Savov, Vasil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Allzen, E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    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 studies2012In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 59, no 3, p. 2962-2973Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 13.
    Brooks, Samantha J
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Solstrand Dahlberg, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Swenne, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Aronsson, Marianne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Zarei, Sanaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lundberg, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Jacobsson, Josefin A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Salonen-Ros, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Rosling, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Obsessive-compulsivity and working memory are associated with differential prefrontal cortex and insula activation in adolescents with a recent diagnosis of an eating disorder2014In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 224, no 3, p. 246-253Article in journal (Refereed)
    Abstract [en]

    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.

  • 14.
    Brooks, Samantha J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. UCT Department of Psychiatry and Mental Health Groote Schuur Hospital Cape Town South Africa.
    Wiemerslage, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Burch, K H
    Maiorana, S A
    Cocolas, E
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kamaloodien, K
    Stein, D J
    The impact of cognitive training in substance use disorder: the effect of working memory training on impulse control in methamphetamine users2017In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 234, no 12, p. 1911-1921Article in journal (Refereed)
    Abstract [en]

    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.

  • 15.
    Brooks, Samantha Jane
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi Birgir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    A debate on current eating disorder diagnoses in light of neurobiological findings: is it time for a spectrum model?2012In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 12, p. 76-Article in journal (Refereed)
    Abstract [en]

    Background: Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV). Instead they are diagnosed as 'eating disorders not otherwise specified' (EDNOS). Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment. Discussion: Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a) current issues in the classification of eating disorders in the DSM-IV, b) changes proposed for DSM-V, c) neuroimaging eating disorder research and d) genetic eating disorder research. Summary: We outline a novel evidence-based 'impulse control' spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V.

  • 16.
    Brooks, Samantha
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Cape Town, South Africa..
    Lochner, Christine
    Univ Stellenbosch, US UCT MRC Unit Anxiety & Stress Disorders, Stellenbosch, South Africa..
    Shoptaw, Steve
    Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA, USA..
    Stein, Dan J.
    Univ Cape Town, US UCT MRC Unit Anxiety & Stress Disorders, Cape Town, South Africa..
    Using the research domain criteria (RDoC) to conceptualize impulsivity and compulsivity in relation to addiction2017In: Brain Research In Addiction / [ed] Calvey, T Daniels, WMU, ELSEVIER , 2017, p. 177-218Chapter in book (Refereed)
    Abstract [en]

    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.

  • 17.
    Burger, Antoinette
    et al.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Anzio Rd, ZA-7925 Cape Town, South Africa;Univ Cape Town, Inst Neurosci, Cape Town, South Africa.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Anzio Rd, ZA-7925 Cape Town, South Africa.
    Stein, Dan J.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Anzio Rd, ZA-7925 Cape Town, South Africa;MRC Unit Risk & Resilience Mental Disorders, Cape Town, South Africa;Univ Cape Town, Inst Neurosci, Cape Town, South Africa.
    Howells, Fleur M.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, Anzio Rd, ZA-7925 Cape Town, South Africa;Univ Cape Town, Inst Neurosci, Cape Town, South Africa.
    The impact of acute and short-term methamphetamine abstinence on brain metabolites: A proton magnetic resonance spectroscopy chemical shift imaging study2018In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 185, p. 226-237Article in journal (Refereed)
    Abstract [en]

    Background

    Abuse 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.

    Methods

    Adults 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.

    Results

    Acute 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.

    Conclusion

    In 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.

  • 18.
    Chapman, Colin Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha Jane
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi Birgir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lifestyle determinants of the drive to eat: a meta-analysis2012In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, no 3, p. 492-497Article in journal (Refereed)
    Abstract [en]

    Background: Obesity is emerging as the most significant health concern of the 21st century. Although this is attributable in part to changes in our environment-including the increased prevalence of energy-dense food-it also appears that several lifestyle factors may increase our vulnerability to this calorie-rich landscape. Epidemiologic studies have begun to show links between adiposity and behaviors such as television watching, alcohol intake, and sleep deprivation. However, these studies leave unclear the direction of this association. In addition, studies that investigated the acute impact of these factors on food intake have reported a wide variety of effect sizes, from highly positive to slightly negative.

    Objective: The purpose of this article was to provide a meta-analysis of the relation between lifestyle choices and increases in acute food intake.

    Design: An initial search was performed on PubMed to collect articles relating television watching, sleep deprivation, and alcohol consumption to food intake. Only articles published before February 2012 were considered. Studies that took place in a controlled, laboratory setting with healthy individuals were included. Studies were analyzed by using 3 meta-analyses with random-effects models. In addition, a 1-factor ANOVA was run to discover any main effect of lifestyle.

    Results: The 3 most prominent lifestyle factors-television watching, alcohol intake, and sleep deprivation-had significant short-term effects on food intake, with alcohol being more significant (Cohen's d = 1.03) than sleep deprivation (Cohen's d = 0.49) and television watching (Cohen's d = 0.2).

    Conclusions: Our results suggest that television watching, alcohol intake, and sleep deprivation are not merely correlated with obesity but likely contribute to it by encouraging excessive eating. Because these behaviors are all known to affect cognitive functions involved in reward saliency and inhibitory control, it may be that they represent common mechanisms through which this eating is facilitated.

  • 19. Dalvie, Shareefa
    et al.
    Stein, Dan J
    Koenen, Karestan
    Cardenas, Valerie
    Cuzen, Natalie L
    Ramesar, Raj
    Fein, George
    Brooks, Samantha J.
    2Department of Psychiatry and Mental Health, University of Cape Town, Observatory, Cape Town, South Africa.
    The BDNF p.Val66Met polymorphism, childhood trauma, and brain volumes in adolescents with alcohol abuse2014In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 14, article id 328Article in journal (Refereed)
    Abstract [en]

    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.

  • 20.
    Gaudio, Santino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha Jane
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Riva, Giuseppe
    Nonvisual Multisensory Impairment of Body Perception in Anorexia Nervosa: A Systematic Review of Neuropsychological Studies2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, p. e110087-Article in journal (Refereed)
    Abstract [en]

    Background: Body image distortion is a central symptom of Anorexia Nervosa (AN). Even if corporeal awareness is multisensory majority of AN studies mainly investigated visual misperception. We systematically reviewed AN studies that have investigated different nonvisual sensory inputs using an integrative multisensory approach to body perception. We also discussed the findings in the light of AN neuroimaging evidence. Methods: Pub Med and PsycINFO were searched until March, 2014. To be included in the review, studies were mainly required to: investigate a sample of patients with current or past AN and a control group and use tasks that directly elicited one or more nonvisual sensory domains. Results:Thirteen studies were included. They studied a total of 223 people with current or past AN and 273 control subjects. Overall, results show impairment in tactile and proprioceptive domains of body perception in AN patients. lnteroception and multisensory integration have been poorly explored directly in AN patients. A limitation of this review is the relatively small amount of literature available. Conclusions: Our results showed that AN patients had a multisensory impairment of body perception that goes beyond visual misperception and involves tactile and proprioceptive sensory components. Furthermore, impairment of tactile and proprioceptive components may be associated with parietal cortex alterations in AN patients. Interoception and multisensory integration have been weakly explored directly. Further research, using multisensory approaches as well as neuroimaging techniques, is needed to better define the complexity of body image distortion in AN. Key Findings: The review suggests an altered capacity of AN patients in processing and integration of bodily signals: body parts are experienced as dissociated from their holistic and perceptive dimensions. Specifically, it is likely that not only perception but memory, and in particular sensorimotor/proprioceptive memory, probably shapes bodily experience in patients with AN.

  • 21.
    Gaudio, Santino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Campus Biomed Roma, Ctr Integrated Res, Area Diagnost Imaging, Via Alvaro Portillo 200, I-00133 Rome, Italy..
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Dept Psychiat & Mental Hlth, Old Groote Schuur Hosp, Psychiat Neuroimaging Grp, Anzio Rd, ZA-7925 Cape Town, South Africa..
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    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 integration2016In: Neuroscience and Biobehavioral Reviews, ISSN 0149-7634, E-ISSN 1873-7528, Vol. 71, p. 578-589Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 22.
    Heany, Sarah J.
    et al.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa..
    van Honk, Jack
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa.;Univ Utrecht, Dept Psychol, Utrecht, Netherlands.;Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa..
    Stein, Dan J.
    Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa..
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Univ Cape Town, Groote Schuur Hosp, Dept Psychiat & Mental Hlth, J2,Anzio Rd, ZA-7925 Cape Town, South Africa..
    A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain2016In: Metabolic brain disease, ISSN 0885-7490, E-ISSN 1573-7365, Vol. 31, no 1, p. 157-167Article in journal (Refereed)
    Abstract [en]

    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.

  • 23.
    Hogenkamp, Pleunie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Cedernaes, Jonathan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chapman, Colin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Vogel, Heike
    Department of Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg.
    Hjorth, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Zarei, Sanaz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lundberg, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dickson, Suzanne
    Department of Physiology/Endocrinology, The Sahlgrenska Academy at the University of Gothenburg.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Calorie anticipation alters food intake after low-caloric but not high-caloric preloads2013In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 8, p. 1548-1553Article in journal (Refereed)
    Abstract [en]

    Objective: Cognitive factors and anticipation are known to influence food intake. The current study examined the effect of anticipation and actual consumption of food on hormone (ghrelin, cortisol, insulin) and glucose levels, appetite and ad libitum intake, to assess whether changes in hormone levels might explain the predicted differences in subsequent food intake.

    Design and Methods: During four breakfast sessions, participants consumed a yogurt preload that was either low-caloric (LC; 180 kcal/300 g) or high-caloric (HC; 530 kcal/300 g), and were provided with either consistent or inconsistent calorie information (i.e. stating the caloric content of the preload was low or high). Appetite ratings and hormone and glucose levels were measured at baseline (t=0), after providing the calorie information about the preload (t=20), after consumption of the preload (t=40) and just before ad libitum intake (t=60).

    Results: Ad libitum intake was lower after HC preloads (as compared to LC preloads; p<0.01). Intake after LC preloads was higher when provided with (consistent) LC-information (467±254 kcal) as compared to (inconsistent) HC-information (346±210 kcal), but intake after the HC preloads did not depend on the information provided (LC-info: 290±178 kcal, HC-info: 333±179 kcal; caloric load*information p=0.03). Hormone levels did not respond in an anticipatory manner, and the post-prandial responses depended on actual calories consumed.

    Conclusions: These results suggest that both cognitive and physiological information determine food intake. When actual caloric intake was sufficient to produce physiological satiety, cognitive factors played no role; however, when physiological satiety was limited, cognitively-induced satiety reduced intake to comparable levels.

  • 24.
    Jacobsson, Josefin A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sällman Almén, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hedberg, Lilia A.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Fredriksson, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Detailed Analysis of Variants in FTO in Association with Body Composition in a Cohort of 70-Year-Olds Suggests a Weakened Effect among Elderly2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 5, p. e20158-Article in journal (Refereed)
    Abstract [en]

    Background

     The rs9939609 single-nucleotide polymorphism (SNP) in the fat mass and obesity (FTO) gene has previously been associated with higher BMI levels in children and young adults. In contrast, this association was not found in elderly men. BMI is a measure of overweight in relation to the individuals' height, but offers no insight into the regional body fat composition or distribution.

    Objective

    To examine whether the FTO gene is associated with overweight and body composition-related phenotypes rather than BMI, we measured waist circumference, total fat mass, trunk fat mass, leg fat mass, visceral and subcutaneous adipose tissue, and daily energy intake in 985 humans (493 women) at the age of 70 years. In total, 733 SNPs located in the FTO gene were genotyped in order to examine whether rs9939609 alone or the other SNPs, or their combinations, are linked to obesity-related measures in elderly humans.

    Design

    Cross-sectional analysis of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort.

    Results

     Neither a single SNP, such as rs9939609, nor a SNP combination was significantly linked to overweight, body composition-related measures, or daily energy intake in elderly humans. Of note, these observations hold both among men and women.

    Conclusions

    Due to the diversity of measurements included in the study, our findings strengthen the view that the effect of FTO on body composition appears to be less profound in later life compared to younger ages and that this is seemingly independent of gender.

  • 25.
    Meneguzzo, Paolo
    et al.
    Department of Neuroscience, University of Padua, Padova, Italy.
    Tsakiris, Manos
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stein, Dan J
    Brooks, Samantha
    Department of Psychiatry and Mental Health, University of Cape Town, Anzio Road, Cape Town 7995, South Africa.
    Subliminal versus supraliminal stimuli activate neural responses in anterior cingulate cortex, fusiform gyrus and insula: a meta-analysis of fMRI studies2014In: BMC Psychology, E-ISSN 2050-7283, Vol. 2, no 1, article id 52Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Non-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.

    METHODS

    We 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.

    RESULTS

    The 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.

    CONCLUSIONS

    Non-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.

  • 26.
    Nordenskjöld, Richard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Simmons, Andrew
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Intracranial volume estimated with commonly used methods could introduce bias in studies including brain volume measurements2013In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 83, p. 355-360Article in journal (Refereed)
    Abstract [en]

    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.

  • 27.
    Schiöth, Helgi B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Craft, Suzanne
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Frey, William H., II
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brain Insulin Signaling and Alzheimer's Disease: Current Evidence and Future Directions2012In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 46, no 1, p. 4-10Article in journal (Refereed)
    Abstract [en]

    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.

  • 28.
    Schiöth, Helgi B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Frey, William H.
    HealthPartners Res Fdn, Alzheimers Res Ctr Reg Hosp, St Paul, MN USA.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Insulin to treat Alzheimer's disease: just follow your nose?2012In: Expert Review of Clinical Pharmacology, ISSN 1751-2433, E-ISSN 1751-2441, Vol. 5, no 1, p. 17-20Article, review/survey (Refereed)
    Abstract [en]

    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.

  • 29.
    Schiöth, Helgi Birgir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha Jane
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Healthcare systems never sleep: are medical residents today the patients of tomorrow?2012In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 13, no 7, p. 965-965Article in journal (Refereed)
  • 30.
    Solstrand Dahlberg, Linda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Wiemerslage, Lyle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Swenne, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsen, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Stark, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Rask-Andersen, Mathias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Salonen-Ros, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
    Adolescents newly diagnosed with eating disorders have structural differences in brain regions linked with eating disorder symptoms2017In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 71, no 3, p. 188-196Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adults with eating disorders (ED) show brain volume reductions in the frontal, insular, cingulate, and parietal cortices, as well as differences in subcortical regions associated with reward processing. However, little is known about the structural differences in adolescents with behavioural indications of early stage ED.

    AIM: This is the first study to investigate structural brain changes in adolescents newly diagnosed with ED compared to healthy controls (HC), and to study whether ED cognitions correlate with structural changes in adolescents with ED of short duration.

    METHODS: Fifteen adolescent females recently diagnosed with ED, and 28 age-matched HC individuals, were scanned with structural magnetic resonance imaging (MRI). Whole-brain and region-of-interest analyses were conducted using voxel-based morphometry (VBM). ED cognitions were measured with self-report questionnaires and working memory performance was measured with a neuropsychological computerized test.

    RESULTS AND CONCLUSIONS: The left superior temporal gyrus had a smaller volume in adolescents with ED than in HC, which correlated with ED cognitions (concerns about eating, weight, and shape). Working memory reaction time correlated positively with insula volumes in ED participants, but not HC. In ED, measurements of restraint and obsession was negatively correlated with temporal gyrus volumes, and positively correlated with cerebellar and striatal volumes. Thus, adolescents with a recent diagnosis of ED had volumetric variations in brain areas linked to ED cognitions, obsessions, and working memory. The findings emphasize the importance of early identification of illness, before potential long-term effects on structure and behaviour occur.

  • 31.
    Suda, Masashi
    et al.
    Kings Coll London, Inst Psychiat, Sect Eating Disorders, London WC2R 2LS, England..
    Brooks, Samantha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology. Uppsala Univ, Dept Neurosci, Uppsala, Sweden..
    Giampietro, Vincent
    Kings Coll London, Inst Psychiat, Ctr Neuroimaging Studies, London WC2R 2LS, England..
    Uher, Rudolf
    Kings Coll London, Inst Psychiat, Sect Eating Disorders, London WC2R 2LS, England..
    Mataix-Cols, David
    Kings Coll London, Dept Psychosis Studies, London WC2R 2LS, England.;Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England..
    Brammer, Michael J.
    Kings Coll London, Inst Psychiat, Ctr Neuroimaging Studies, London WC2R 2LS, England..
    Williams, Steven C. R.
    Kings Coll London, Inst Psychiat, Ctr Neuroimaging Studies, London WC2R 2LS, England..
    Treasure, Janet
    Kings Coll London, Inst Psychiat, Sect Eating Disorders, London WC2R 2LS, England..
    Campbell, Iain C.
    Kings Coll London, Inst Psychiat, Sect Eating Disorders, London WC2R 2LS, England..
    Provocation of Symmetry/Ordering Symptoms in Anorexia nervosa: A Functional Neuroimaging Study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, article id e97998Article in journal (Refereed)
    Abstract [en]

    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.

  • 32. Suda, Masashi
    et al.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Giampietro, Vincent
    Friederich, Hans-Christoph
    Uher, Rudolf
    Brammer, Michael J.
    Williams, Steven C. R.
    Campbell, Iain C.
    Treasure, Janet
    Functional Neuroanatomy of Body Checking in People with Anorexia Nervosa2013In: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 46, no 7, p. 653-662Article in journal (Refereed)
    Abstract [en]

    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.

  • 33.
    Titova, Olga E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ax, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Mediterranean diet habits in older individuals: Associations with cognitive functioning and brain volumes2013In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 48, no 12, p. 1443-1448Article in journal (Refereed)
    Abstract [en]

    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.

  • 34.
    Titova, Olga E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Ayvazova, Elena A.
    Bichkaeva, Fatima A.
    Brooks, Samantha J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Chumakova, Galina N.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices2012In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 108, no 8, p. 1341-1345Article in journal (Refereed)
    Abstract [en]

    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.

  • 35.
    Titova, Olga E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Hjorth, Olof C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Anorexia nervosa is linked to reduced brain structure in reward and somatosensory regions: a meta-analysis of VBM studies2013In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 13, no 1, p. 110-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Structural imaging studies demonstrate brain tissue abnormalities in eating disorders, yet a quantitative analysis has not been done.

    METHODS

    In 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.

    RESULTS

    Anorexia 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.

    CONCLUSIONS

    Global 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.

  • 36.
    Titova, Olga E
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Brooks, Samantha J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ax, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Elna-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Schiöth, Helgi B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Benedict, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Dietary intake of eicosapentaenoic and docosahexaenoic acids is linked to gray matter volume and cognitive function in elderly2013In: Age (Omaha), ISSN 0161-9152, E-ISSN 1574-4647, Vol. 35, no 4, p. 1495-1505Article in journal (Refereed)
    Abstract [en]

    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.

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