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  • 1. Bas-Hoogendam, Janna Marie
    et al.
    van Steenbergen, Henk
    Pannekoek, J. Nienke
    Fouche, Jean-Paul
    Lochner, Christine
    Hattingh, Coenraad J.
    Cremers, Henk R.
    Furmark, Tomas
    Månsson, Kristoffer N. T.
    Frick, Andreas
    Engman, Jonas
    Boraxbekk, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Carlbring, Per
    Andersson, Gerhard
    Fredrikson, Mats
    Straube, Thomas
    Peterburs, Jutta
    Klumpp, Heide
    Phan, K. Luan
    Roelofs, Karin
    Stein, Dan J.
    van der Wee, Nic. J. A.
    Sample Size Matters: A Voxel-Based Morphometry Multi-Center Mega-Analysis of Gray Matter Volume in Social Anxiety Disorder2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S7-S7Article in journal (Refereed)
  • 2.
    Elgh, Eva
    et al.
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
    Lindqvist Åstot, Ann
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
    Fagerlund, Markku
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Eriksson, Sture
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation, Geriatric Medicine.
    Olsson, Tommy
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Näsman, Birgitta
    Umeå University, Faculty of Medicine, Community Medicine and Rehabilitation.
    Cognitive dysfunction, hippocampal atrophy and glucocorticoid feedback in Alzheimer's disease.2006In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 59, no 2, p. 155-161Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The hippocampal formation is damaged early in Alzheimer's disease (AD). An association between temporal lobe volume and cognitive function has been shown in several studies. Increased limbic-hypothalamic-pituitary-adrenal (LHPA) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment. Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory (episodic and visuospatial) and decreased feedback sensitivity in the LHPA axis in AD. METHODS: Sixteen medication-free outpatients with mild to moderate AD were included. Hippocampal volume was measured with magnetic resonance imaging. Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone. Three different components in the neuropsychological battery -- Rey 15 item memory test, Alzheimer's Disease Assessment Scale (ADAS) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument (WAIS-R NI) -- were found to represent episodic and visuospatial memory. RESULTS: Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes. No association was found between LHPA feedback and hippocampal volume. CONCLUSIONS: Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimer's disease.

  • 3.
    Engström, Christer
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Åström, Monica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordqvist-Karlsson, Barbro
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nylander, Per- Olof
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Relationship between prophylactic effect of lithium therapy and family history of affective disorders.1997In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 42, no 6, p. 425-433Article in journal (Refereed)
    Abstract [en]

    Lithium therapy response and age of onset (AOO) were studied in 98 patients with bipolar affective disorder (BPAD) who were divided into subgroups depending on type of family history of affective disorders. The highest (33.0 years) and lowest (25.5 years) age of onset were found in nonfamilial patients and in familial patients with a first-degree relative of BPAD, respectively. Nonfamilial patients showed the best response to lithium. There were 0.9 episodes/year off lithium compared to 0.3 episodes/year on lithium (an 88% decrease). A poorer response (a 71% decrease; a reduction from 1.39 episodes per year off lithium to 0.65 on lithium) was found in familial patients with a first-degree relative of BPAD. Differences in serum lithium values between the groups could not explain the observed differences. Thus, familial patients showed a more severe manifestation of the disease with an earlier AOO and a lower prophylactic effect of lithium.

  • 4.
    Fischer, Håkan
    et al.
    Karolinska Institute.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Karlsson, Sari
    Karolinska Institute.
    Karlsson, Per
    Karolinska Hospital.
    Brehmer, Yvonne
    Karolinska Institute.
    Rieckmann, Anna
    Karolinska Institute.
    Macdonald, Stuart WS
    University of Victoria.
    Farde, Lars
    Karolinska Hospital.
    Bäckman, Lars
    Karolinska Institute.
    Simulating neurocognitive aging: effects of a dopaminergic antagonist on brain activity during working memory2010In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 67, no 6, p. 575-580Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity.

    METHODS: We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults.

    RESULTS: An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response.

    CONCLUSIONS: These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.

  • 5. Ho, Tiffany C
    et al.
    Connolly, Colm G
    Henje Blom, Eva
    Karolinska Institutet, University of California San Francsisco.
    LeWinn, Kaja Z
    Strigo, Irina A
    Paulus, Martin P
    Frank, Guido
    Max, Jeffrey E
    Wu, Jing
    Chan, Melanie
    Tapert, Susan F
    Simmons, Alan N
    Yang, Tony T
    Emotion-Dependent Functional Connectivity of the Default Mode Network in Adolescent Depression.2015In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 78, no 9, p. 635-46, article id S0006-3223(14)00697-0Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Functional magnetic resonance imaging research suggests that major depressive disorder (MDD) in both adults and adolescents is marked by aberrant connectivity of the default mode network (DMN) during resting state. However, emotional dysregulation is also a key feature of MDD. No studies to date have examined emotion-related DMN pathology in adolescent depression. Comprehensively understanding the dynamics of DMN connectivity across brain states in individuals with depression with short disease histories could provide insight into the etiology of MDD.

    METHODS: We collected functional magnetic resonance imaging data during an emotion identification task and during resting state from 26 medication-free adolescents (13-17 years old) with MDD and 37 well-matched healthy control subjects. We examined between-group differences in blood oxygenation level-dependent task responses and emotion-dependent and resting-state functional connectivity of the two primary nodes of the DMN: medial prefrontal cortex and posterior cingulate cortex (PCC). Additionally, we examined between-group differences in DMN functional connectivity and its relationship to depression severity and onset.

    RESULTS: Relative to healthy control subjects, unmedicated adolescents with MDD demonstrated reduced medial prefrontal cortex and PCC emotion-related deactivation and greater medial prefrontal cortex and PCC emotion-dependent functional connectivity with precuneus, cingulate gyrus, and striatum/subcallosal cingulate gyrus. The PCC-subcallosal cingulate connectivity remained inflexibly elevated in the subjects with MDD versus healthy control subjects during resting state. Stronger PCC emotion-dependent functional connectivity was associated with greater depression severity and an earlier age of depression onset.

    CONCLUSIONS: Adolescent depression is associated with inflexibly elevated DMN connections. Given more recent evidence of DMN maturation throughout adolescence, our findings suggest that early-onset depression adversely affects normal development of functional brain networks.

  • 6. Johansson, Carolina
    et al.
    Willeit, Matthäeus
    Aron, Liviu
    Smedh, Christina
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Ekholm, Jenny
    Paunio, Tiina
    Kieseppa, Tuula
    Lichtermann, Dirk
    Praschak-Rieder, Nicole
    Neumeister, Alexander
    Kasper, Siegfried
    Peltonen, Leena
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Partonen, Timo
    Schalling, Martin
    Seasonal affective disorder and the G-protein beta-3-subunit C825T polymorphism2004In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 55, no 3, p. 317-319Article in journal (Refereed)
    Abstract [en]

    Background: Guanine nucleotide-binding proteins (G-proteins) have been implicated in affective disorders, with reports of altered signal transduction and G-protein levels. Association with seasonal affective disorder (SAD) has been found for the higher activity T-allele of the G-protein beta-3-subunit C825T polymorphism.

    Methods. European SAD patients (n = 159) and matched controls (n = 159) were genotyped for the C825T. Seasonality and diurnal preference were investigated in subsets of the material (n = 177 and 92, respectively).

    Results. We found no association between C825T and SAD (chi(2) = .09, p = .96) or seasonality (F = 1.76, p = .18). There was some evidence for an effect on diurnal preference but only in the control group (n = 46, t = - 2.8, Bonferroni corrected p = .045).

    Conclusions: These results suggest that the G-protein beta-3-subunit 825 T-allele does not play a major role in susceptibility to seasonal affective disorder in the population studied.

  • 7. Lindner, Philip
    et al.
    Flodin, Pär
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Larm, Peter
    Budhiraja, Meenal
    Savic, Ivanka
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Tiihonen, Jari
    Hodgins, Sheilagh
    Disentangling Associations between Antisocial Behavior and Anxiety Disorders with Amygdala-Orbitofrontal Functional and Structural Connectivity in Females2017In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S98-S98Article in journal (Refereed)
  • 8.
    Mansson, Kristoffer N.
    et al.
    Linköping, Sweden.
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Stockholm, Sweden.
    Frick, Andreas
    Uppsala, Sweden.
    Carlbring, Per
    Stockholm, Sweden.
    Furmark, Tomas
    Uppsala, Sweden.
    Olsson, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Gerhard
    Linköping, Sweden; Stockholm, Sweden.
    Interrelated Functional and Structural Amygdala Plasticity Following Internet-delivered Cognitive Behavior Therapy for Social Anxiety Disorder2015In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 77, no 9 Suppl., p. 51S-51SArticle in journal (Other academic)
  • 9. Mansson, Kristoffer N. T.
    et al.
    Carlbring, Per
    Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden.
    Frick, Andreas
    Engman, Jonas
    Olsson, Carl-Johan
    Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Furmark, Tomas
    Andersson, Gerhard
    Amygdala Changes After Cognitive Behavior Therapy and Attention Bias Modification via the Internet: An fMRI-Study2013In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 73, no 9, p. 72S-72SArticle in journal (Refereed)
  • 10. Nilsson, Kent W
    et al.
    Sjöberg, Rickard L
    Damberg, Mattias
    Leppert, Jerzy
    Ohrvik, John
    Alm, Per Olof
    Lindström, Leif
    Oreland, Lars
    Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity.2006In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 59, no 2Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A number of important sociological, psychological, and biological predictors of adolescent criminal behavior have been identified during the most recent decades. The aim of this study was to replicate recent findings that interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter region and psychosocial factors might predict male adolescent criminal activity.

    METHODS: A cross-sectional study with a randomized sample from the total population of 16- and 19-year-olds from the county of Västmanland, Sweden. Eighty-one male adolescents, who volunteered to participate, were randomly selected from groups representing different degrees of deviant risk behavior.

    RESULTS: The present study strongly supports the notion that carrying the 3-repeat allele of the MAO-A-gene promoter increases the risk of male adolescent criminal behavior, when interacting with psychosocial factors. No effects at all of the MAO-A genotype on adolescent criminal activity were found when MAO-A genotype was considered alone (i.e., without its psychosocial context). The explained variance of the bio-psychosocial model (controlling for MAO-A) in this study exceeded the psychosocial model by 12%.

    CONCLUSIONS: The findings support the notion that genotype and psychosocial factors interact to precipitate male adolescent criminal behavior.

  • 11. Schwandt, Melanie L
    et al.
    Lindell, Stephen G
    Sjöberg, Rickard L
    Chisholm, Kelli L
    Higley, J Dee
    Suomi, Stephen J
    Heilig, Markus
    Barr, Christina S
    Gene-environment interactions and response to social intrusion in male and female rhesus macaques.2010In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 67, no 4Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat.

    METHODS: Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated.

    RESULTS: Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing.

    CONCLUSIONS: Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.

  • 12. Smedh, K
    et al.
    Spigset, O
    Allard, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Mjörndal, T
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.1999In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 45, no 4, p. 464-70Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Seasonal affective disorder (SAD) has been regarded as a melatonin disorder, but the pathophysiological mechanisms of SAD are to a large extent unclarified. Serotonergic mechanisms have also been studied, but they have shown inconsistent results. METHODS: We have compared [3H]paroxetine and [3H]lysergic acid diethylamide (LSD) binding in platelets from 23 SAD patients and 23 controls. Then SAD patients had 4 weeks of light therapy. On the last treatment day new blood samples were drawn. Symptoms before and after light treatment were measured by SIGH-SAD. RESULTS: Bmax for paroxetine binding before light treatment was higher in SAD patients compared to controls and also higher in responders than in nonresponders. Bmax decreased significantly during light treatment. We also found a negative correlation between the two Bmax values before but not after light treatment. There was a negative correlation between Bmax for paroxetine binding before treatment and clinical status after treatment. Patients with reduced Bmax for LSD binding after treatment had a better clinical treatment response. CONCLUSIONS: The present study indicates that serotonin receptor parameters might be suitable in the prediction of clinical response to light treatment.

  • 13. Spigset, O
    et al.
    Allard, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Mjörndal, T
    Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers.1998In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 43, no 10, p. 774-80Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Circannual variations occur in several serotonergic parameters, including platelet serotonin uptake and platelet [3H]imipramine binding. METHODS: Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites were studied longitudinally for 1 year in 12 healthy volunteers. RESULTS: For [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal variation (two-way analysis of variance), although Bmax was significantly higher during the months October through February than during the months April through August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg protein) and minimum in February (1168 fmol/mg protein). The affinity constant (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p = .08) and were significantly negatively correlated for Kd (r = -.88; p = .009). CONCLUSIONS: The present study demonstrates a seasonal effect on platelet serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A receptor binding. The results imply that circannual fluctuations should be taken into account when these platelet serotonin markers are studied.

  • 14.
    Wikgren, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Maripuu, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Karlsson, Thomas
    Linköping University, Department of Behavioral Sciences and Learning.
    Nordfjäll, Katarina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergdahl, Jan
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Del-Favero, Jurgen
    VIB, Department of Molecular Genetics.
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Lars-Göran
    Stockholm University, Department of Psychology .
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Short telomeres in depression and the general population are associated with a hypocortisolemic state2012In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 71, no 4, p. 294-300Article in journal (Refereed)
    Abstract [en]

    Background: The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in stress regulation, and leukocyte telomere length (TL) has been suggested to represent a cumulative measure of stress. Depression is intimately related with stress and frequently exhibits a dysregulated HPA axis. We aimed to study the relationships between TL and biological and psychological facets of stress in recurrent major depressive disorder and controls.

    Methods: Leukocyte TL was measured in 91 subjects with recurrent major depressive disorder and 451 control subjects. Stress was assessed from both a biological perspective, by assessing HPA axis function with a weight-adjusted very-low-dose dexamethasone suppression test (DST), and a psychological perspective, with self-report questionnaires.

    Results: TL was shorter among patients compared with control subjects (277 base pairs, p = .001). Overall, short TL was associated with a hypocortisolemic state (low post-DST cortisol and high percentage of cortisol reduction after the DST) among both patients and control subjects but more pronounced among patients. This state, which was overrepresented among patients, was characterized by high familial loading of affective disorders among patients (p = .001) and high C-reactive protein levels among control subjects (p = .040). TL was also inversely associated with stress measured with the Perceived Stress Questionnaire (rs = −.258, p = .003).

    Conclusions: Short TL is associated with depression and hypocortisolism. Because hypocortisolism has been shown to develop from chronic stress exposure, our findings corroborate the concept of TL as a cumulative measure of stress and provide novel insights into the detrimental role of stress in depressive illness and the general population.

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