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  • 1.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Clinical studies and chemical pathology in normal aging and dementia of Alzheimer type1980Doctoral thesis, comprehensive summary (Other academic)
  • 2.
    Adolfsson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bejerot, Susanne
    Engel, Jörgen
    Forssberg, Hans
    Heilig, Markus
    Humble, Mats
    Ingvar, Martin
    Levander, Sten
    Oreland, Lars
    Pedersen, Nancy
    Asberg, Marie
    Ohman, Arne
    [Researchers and psychiatrists defending Gillberg's research on ADDH: Karfve's campaign is a form of personal persecution and scientific basis is missing]2003In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 100, no 8, 636-7 p.Article in journal (Refereed)
  • 3.
    Adolfsson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, M
    [Psychiatry must offer a qualified ambulatory care to the elderly]1990In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 87, no 47, 3962, 3967- p.Article in journal (Refereed)
  • 4.
    Adolfsson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Gustafson, L
    Skoog, I
    Viitanen, M
    Wallin, A
    [A check list for diagnosis and basic investigation of dementia in primary health care]1990In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 87, no 48, 4098-9 p.Article in journal (Refereed)
  • 5.
    Adolfsson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Holmberg, B
    [Anxiety depressions among the elderly--symptoms, diagnosis and treatment]1991In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 88, no 32-33, 2586, 2590-1 p.Article in journal (Refereed)
  • 6.
    Adolfsson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Linge, E
    [Psychiatric clinics for the elderly need sufficient resources for ambulatory care]1991In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 88, no 7, 491- p.Article in journal (Refereed)
  • 7.
    Alaerts, Maaike
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Ceulemans, Shana
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Forero, Diego
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Moens, Lotte N
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Heyrman, Lien
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    De Rijk, Peter
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Sweden .
    Goossens, Dirk
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Institute for Biotechnology and University of Antwerp, Belgium.
    Support for NRG1 as a susceptibility factor for schizophrenia in a northern Swedish isolated population2009In: Archives of General Psychiatry, ISSN 0003-990X, E-ISSN 1538-3636, Vol. 66, no 8, 828-837 p.Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Neuregulin 1 (NRG1), a growth factor involved in neurodevelopment, myelination, neurotransmitter receptor expression, and synaptic plasticity, first joined the list of candidate genes for schizophrenia when a 7-marker haplotype at the 5' end of the gene (Hap(ICE)) was shown to be associated with the disorder in the Icelandic population. Since then, more genetic and functional evidence has emerged, which supports a role for NRG1 in the development of schizophrenia. OBJECTIVE: To determine the contribution of NRG1 to susceptibility for schizophrenia in a northern Swedish isolated population. DESIGN: Detailed linkage disequilibrium (LD)-based patient-control association study. This is the first study to type and analyze the 7 Hap(ICE) markers and a set of 32 HapMap tagging single-nucleotide polymorphisms (SNPs) that represents variants with a minor allele frequency of at least 1% and fully characterizes the LD structure of the 5' part of NRG1. SETTING: Outpatient and inpatient hospitals. PARTICIPANTS: A total of 486 unrelated patients with schizophrenia and 514 unrelated control individuals recruited from a northern Swedish isolated population. MAIN OUTCOME MEASURES: Association between markers and disease. RESULTS: Analysis of the Hap(ICE) markers showed the association of a 7-marker and 2-microsatellite haplotype, different from the haplotypes associated in the Icelandic population and overrepresented in northern Swedish control individuals. Subsequently, a more detailed analysis that included all 37 genotyped SNPs was performed by investigating haplotypic association, dependent and independent of LD block structure. We found significant association with 5 SNPs located in the second intron of NRG1 (.007

  • 8.
    Alaerts, Maaike
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Ceulemans, Shana
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Forero, Diego
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Moens, Lotte N
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Heyrman, Lien
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Goossens, Dirk
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    De Rijk, Peter
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
    Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population2009In: American journal of medical genetics. Part B, Neuropsychiatric genetics, ISSN 1552-485X, Vol. 150B, no 4, 585-592 p.Article in journal (Refereed)
    Abstract [en]

    Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and I587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.

  • 9. Alafuzoff, I
    et al.
    Almqvist, E
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lake, S
    Wallace, W
    Greenberg, D A
    Winblad, B
    A comparison of multiplex and simplex families with Alzheimer's disease/senile dementia of Alzheimer type within a well defined population.1994In: Journal of neural transmission. Parkinson's disease and dementia section, ISSN 0936-3076, Vol. 7, no 1, 61-72 p.Article in journal (Refereed)
    Abstract [en]

    A study was made on 150 clinically demented patients presenting at autopsy at Umeå University Hospital in Sweden. In 90 of the cases dementia was considered to be primary in nature and of these forty six per cent (41 cases), fulfilled both the clinical and histopathological criteria for the diagnosis of Alzheimer's disease/Senile dementia of Alzheimer type (AD/SDAT). The families of these 41 AD/SDAT cases were then studied, and a family history obtained through interviews with multiple family informants and from civil and medical records. Additional diseased family members suffering from progressive dementia (multiplex families) were observed in 12 probands out of 41 (29%). Multiplex families exhibited similar clinical and histopathological characteristics as simplex families containing a single affected individual. The secondary cases in the multiplex families exhibited similar demographic and clinical characteristics as the probands. 39% of the multiplex and 14% of the simplex cases had an early age of onset of the disease, that was under 65 years. The overall prevalence of progressive dementia disorders in the 41 families was 5.9%. The prevalence of a progressive dementia disorder was 11% in the multiplex families (14% for the early onset cases) and 3.5% in the simplex families (2% for the early onset cases). The prevalence of progressive dementia disorder for family members who had passed the mean age of the onset of the disease for their family, was 45% for multiplex and 18% for simplex families. Furthermore the incidence rate for dementia was significantly higher (p < 0.005) in multiplex families (5.5 per 1,000 person years) when compared to simplex families (2.5 per 1,000 person years). No differences could be seen in parental age at birth of the diseased when comparing the two sets of families. However in multiplex families the duration of the disease was significantly (p < 0.025) shorter, in subjects with parental age at birth over 35 years compared to those with a parental age under 35 years. The multiplex families contained significantly (p < 0.025) larger sibships; and showed a significantly lower age of onset for the disease (p < 0.001), and a significantly longer duration of disease (p < 0.05) compared to the simplex families. A significant intra familial correlation of age at disease onset was observed in both sets of the families.

  • 10. Alafuzoff, I
    et al.
    Iqbal, K
    Friden, H
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Winblad, B
    Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis.1987In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 74, no 3, 209-25 p.Article in journal (Refereed)
    Abstract [en]

    Autopsied brains from 55 patients with dementia between 59-95 years of age (mean age 77.9 +/- 8.1 years) and 19 non-demented individuals between 46-91 years of age (mean age 74.3 +/- 10.5 years) were examined to establish histopathological criteria for normal ageing, primary degenerative [Alzheimer's disease (AD)/senile dementia of Alzheimer type (SDAT)] and vascular (multi-infarct) dementia (MID) disorders. Senile/neuritic plaques, neurofibrillary tangles, microscopic infarcts and perivascular serum protein deposits were quantified in the frontal lobe (Brodmann area 10) and in the hippocampus. The demented patients were classified according to the DSM-III criteria into AD/SDAT and MID. Operationally defined histopathological criteria for dementias, based on the degree/amount of the histopathological changes seen in aged non-demented patients, were postulated. The demented patients were clearly separable into three histopathological types, namely AD/SDAT, MID and AD-MID, the dementia type where both the degenerative and the vascular changes are coexistent in greater extent than are seen in the non-demented individuals. Using general clinical, gross neuroanatomical and histopathological data three separate dementia classes, namely AD/SDAT, MID and AD-MID, were visualized in two-dimensional space by multivariate data analysis. This analysis revealed that the pathology in the AD-MID patients was not merely a linear combination of the pathology in AD/SDAT and MID, indicating that AD-MID might represent a dementia type of its own. The clinical diagnosis for AD/SDAT and MID was certain in only half of the AD/SDAT and one third of the MID cases when evaluated histopathologically and by multivariate data analysis. AD/SDAT, MID and AD-MID were histopathologically diagnosed in 49%, 24% and 27%, respectively, of all the dementia cases studied. Opposite correlation between the number of tangles, plaques and the patient age in non-demented and AD/SDAT cases were observed, indicating that the pathogenesis of tangles and plaques in the two groups of patients might be different and that AD/SDAT might not be a form of an exaggerated ageing process.

  • 11. Andersson, A
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, K
    Marcusson, J
    Platelet [3H]paroxetine binding to 5-HT uptake sites in Alzheimer's disease.1991In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 12, no 5, 531-4 p.Article in journal (Refereed)
    Abstract [en]

    Platelet serotonin (5-hydroxytryptamine, 5-HT) uptake sites were studied in a control group (n = 30) and an Alzheimer group (n = 40) using [3H]paroxetine as radioligand. The maximum number of binding sites (Bmax) for control (1250 +/- 60 fmol/mg protein) was not different from the Alzheimer group (1280 +/- 40 fmol/mg protein). There were no differences in apparent binding affinity (Kd): 0.046 (0.024-0.062) nM for control and 0.040 (0.027-0.061) nM for Alzheimer. Thus even though several previous studies have demonstrated marked atrophy of 5-HT containing neurites and 5-HT uptake sites in Alzheimer's disease, these findings are not found in the periphery on platelets. The platelet 5-HT uptake site cannot be used as a peripheral marker of Alzheimer's disease.

  • 12. Aström, S
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Sandman, P O
    Wedman, I
    Winblad, B
    Attitudes of health care personnel toward demented patients.1987In: Comprehensive gerontology. Section B, Behavioural, social, and applied sciences, ISSN 0902-008X, Vol. 1, no 3, 94-9 p.Article in journal (Refereed)
    Abstract [en]

    Health care personnel (n = 724) working in psychogeriatric care, somatic and psychiatric long-term care, somatic and psychiatric general care and in homes for the aged, were interviewed by means of questionnaires evaluating attitudes and intentions regarding work with demented patients and education in their care. The overall attitude towards demented patients was positive. The largest numbers of personnel with positive attitudes were found in psychogeriatric care and somatic long-term care and the lowest in general medical and psychiatric care. The figure for positive attitudes in relation to education showed a similar figure for all categories. Given a free choice only 4% of the respondents had the intention of working solely with demented patients. A majority of the respondents reported that their knowledge of the care of demented patients came from clinical work. There is a strong need for further education.

  • 13. Brändström, Sven
    et al.
    Schlette, Paul
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Przybeck, T R
    Lundberg, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Forsgren, Thomas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Sigvardsson, S
    Nylander, P O
    Nilsson, L G
    Cloninger, R C
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Swedish normative data on personality using the Temperament and Character Inventory.1998In: Comprehensive Psychiatry, ISSN 0010-440X, E-ISSN 1532-8384, Vol. 39, no 3, 122-8 p.Article in journal (Refereed)
    Abstract [en]

    The Temperament and Character Inventory (TCI) is a self-report personality questionnaire based on Cloninger's psychobiological model of personality, which accounts for both normal and abnormal variation in the two major components of personality, temperament and character. Normative data for the Swedish TCI based on a representative Swedish sample of 1,300 adults are presented, and the psychometric properties of the questionnaire are discussed. The structure of the Swedish version replicates the American version well for the means, distribution of scores, and relationships within the between scales and subscales. Further, the Swedish inventory had a reliable factor structure and test-retest performance. The results of this study confirm the theory of temperament and character as a seven-factor model of personality.

  • 14. Börjesson, A
    et al.
    Karlsson, T
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Rönnlund, Michael
    Nilsson, L
    Linopirdine (DUP 996): cholinergic treatment of older adults using successive and non-successive tests.1999In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 40, no 2, 78-85 p.Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to examine whether cholinergic treatment of age-associated memory impairment with Linopirdine (DUP 996), a derivate of phenylindoline, affects explicit memory, implicit memory, and primary memory. We also assessed cognitive decision making in a reaction time test. Explicit memory was assessed by face recognition, word recall and a word recognition test, being part of a successive test paradigm. Implicit memory was assessed by primed word fragment completion in the same successive test paradigm. Primary memory was studied by means of digit recall. Thirty-eight elderly subjects fulfilled the criteria for memory impairment. Four groups of subjects were given 10, 20 or 30 mg of DUP 996 or placebo during 4 weeks. A double-blind procedure was applied. No significant treatment effects for recognition memory and priming were obtained in the successive test paradigm. Analysis of dependence/independence between tests did not show any clear pattern of treatment effects. The other explicit memory tests and the reaction time test showed no effect with DUP 996. Because of the range of the different tests used here, the result and the general evidence in other investigations of the cholinergic depletion among aged people, the conclusion is that DUP 996 does not improve memory performance either in explicit, implicit or primary tests.

  • 15. Cammaerts, Sophia
    et al.
    Strazisar, Mojca
    Smets, Bart
    Weckhuysen, Sarah
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    De Jonghe, Peter
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    De Rijk, Peter
    Del Favero, Jurgen
    Schizophrenia-Associated MIR204 Regulates Noncoding RNAs and Affects Neurotransmitter and Ion Channel Gene Sets2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, e0144428Article in journal (Refereed)
    Abstract [en]

    As regulators of gene expression, microRNAs (miRNAs) are likely to play an important role in the development of disease. In this study we present a large-scale strategy to identify miRNAs with a role in the regulation of neuronal processes. Thereby we found variant rs7861254 located near the MIR204 gene to be significantly associated with schizophrenia. This variant resulted in reduced expression of miR-204 in neuronal-like SH-SY5Y cells. Analysis of the consequences of the altered miR-204 expression on the transcriptome of these cells uncovered a new mode of action for miR-204, being the regulation of noncoding RNAs (ncRNAs), including several miRNAs, such as MIR296. Furthermore, pathway analysis showed downstream effects of miR-204 on neurotransmitter and ion channel related gene sets, potentially mediated by miRNAs regulated through miR-204.

  • 16.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Converging evidence suggests that monoamine neurotransmitter turnover in human adults is associated with their season of birth.2002In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491, Vol. 252, no 3, 130-4 p.Article in journal (Refereed)
    Abstract [en]

    Separate studies on adults, including those in suicidology and another regarding personality in the general population, have indicated associations with their season of birth. We analyse each of these studies by multiple nonlinear regression employing a cosine function for the month of birth, and compare these studies regarding the birth months giving the maxima and minima. The method of suicide in suicide studies shows a significant month-of-birth variation similar to that for the serotonin metabolite 5-HIAA in the separate study on cerebrospinal fluid, with a peak around the birth month September and a nadir around birth in March. When comparing the personality study with the study on cerebrospinal fluid, the trait novelty seeking varies similar to that for the dopamine metabolite HVA or the norepinephrine metabolite MHPG, and the trait reward dependence varies similar to that for HVA. The trait self-transcendence varies similar to the ratio of the dopamine and serotonin metabolites. Dopamine turnover in adults thus shows a peak around the birth months November-December, and a nadir around the birth months May-June, suggesting a possible involvement of the length of photoperiod during their perinatal period. These results provide strong evidence for the influence of season of birth on adult monoamine neurotransmitter turnover, and give further support for the monoaminergic modulation of the temperament and character traits.

  • 17.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Engström, C
    Ekholm, Birgit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    son Berg, M L
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nylander, P O
    Anticipation in Swedish families with schizophrenia.1995In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 5, no 4, 181-6 p.Article in journal (Refereed)
    Abstract [en]

    Nineteen parent-offspring pairs obtained from 14 two-generation families with available medical records and diagnosis of schizophrenia were studied to compare the ages of onset of the parent generation with those of the offspring generation. The mean age of onset for the parent generation was 37.3 +/- 6.0 years and for the offspring generation was 20.8 +/- 4.4. The mean difference was thus 16.5 +/- 6.2, suggesting the occurrence of anticipation in schizophrenia (p < 0.001). Although some ascertainment biases (like reduced fertility in early-onset parents or early detection of symptoms in offsprings of affected parents) may partially contribute to the occurrence of anticipation, this study replicates recent reports of anticipation in several neuropsychiatric disorders, some of which have been shown to be associated with unstable expansions of trinucleotide repeats in the genomic DNA.

  • 18.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Forsgren, Tomas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, L G
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Season of birth variations in the temperament and character inventory of personality in a general population.2001In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 44, no 1, 19-26 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Since several studies show season of birth variations in morbidity, suicidal behavior and CSF (cerebrospinal fluid) monoamine metabolites, we investigated season of birth variations in personality in the population. METHODS: We analyzed by multiple logistic regressions the Temperament and Character Inventory (TCI) for 2,130 individuals taking part in the Betula prospective random cohort study of Umeå, Sweden. RESULTS: The personality dimensions were correlated significantly with age and gender. We stratified the data according to age, gender and the season of TCI measurement. By the median split in each stratum, a high-value group and a low-value group were obtained for each of the personality dimensions. Those born during February to April were significantly more likely than those born during October to January to have high NS (novelty seeking) among women, particularly the subscale NS2 (impulsiveness vs. reflection), and to have high PS (persistence) among men. Temperament profiles also showed season of birth variations. CONCLUSIONS: We discuss the associations in the literature between personality and the monoamines serotonin and dopamine, and suggest that our results are compatible with a hypothesis of season of birth variation in the monoamine turnover. The personality traits are likely to be influenced by several genetic and environmental factors, one of them being the season of birth.

  • 19.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jonasson, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolescent attachment styles and their relation to the temperament and character traits of personality in a general population.2005In: Eur Psychiatry, ISSN 0924-9338, Vol. 20, no 3, 251-9 p.Article in journal (Refereed)
  • 20.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jonasson, Mattias
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    The Temperament Scale of Novelty Seeking in adolescents shows an association with season of birth opposite to that in adults.2002In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 111, no 1, 45-54 p.Article in journal (Refereed)
    Abstract [en]

    We investigated the relationship between season of birth and the Junior Temperament and Character Inventory of Personality (Junior TCI, JTCI) in adolescents. The Temperament Scale of Novelty Seeking (NS) is significantly higher for females born during October-January as compared to females born otherwise. This association is opposite to that obtained earlier for adults. For both genders pooled, NS is significantly higher for those born during October-March compared to April-September. This association is also found when examining the data for those of age up to 18 years in a third independent study on the age range 11-81 years with the adult TCI. There is a greater tendency for exploration and risk-taking behavior as the child individuates from the family. Our study suggests that the effects of such environmental and developmental changes on personality are different in those born during October-March as compared to those born during April-September. The former show a higher rise in NS during adolescence and a steeper fall in NS during the years of adulthood, compared to the latter. Dopamine turnover is likely associated with NS, and the mutually inhibitory systems of dopamine and melatonin are the paracrine signals of day and night, respectively. Thus, the maternal entrainment of these systems during the prenatal period, or the postnatal environmental influence on these systems, may be different for those born during the short photoperiod of October-March as compared to those born during the long photoperiod part of the year.

  • 21.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Smedh, Kristina
    Johansson, Carolina
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    An epidemiological study on gender differences in self-reported seasonal changes in mood and behaviour in a general population of northern Sweden.2004In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 58, no 6, 429-37 p.Article in journal (Refereed)
    Abstract [en]

    Gender differences have been reported regarding symptoms, prevalence and heritability of seasonal affective disorders (SAD). We focus on gender aspects in this study of self-reported seasonal changes in mood and behaviour in a general population. The Seasonal Pattern Assessment Questionnaire (SPAQ) was completed by 2620 adults (55.6% women) aged 35-85 years, enrolled in the Betula prospective random cohort study of Umeå, Sweden. October to February turned out to be suitable winter months. SAD was found in 2.2% and sub-syndromal SAD (S-SAD) in 5.7%. Women had about 1.5 times higher prevalences than men, and seasonality problems decreased with age in both genders. Preference for eating least was distributed with a peak in summer, whereas preference for eating most had a major peak in winter (winter eaters) and a minor peak in summer (summer eaters). Significantly more of winter eaters in women, and significantly more of summer eaters in men, felt worst in winter. Seasonal change in weight was considered significantly as a problem by women but not by men. Winter behaviour of sleeping most was considered significantly as a problem by men but not by women. Women reacted significantly to temperature-related changes (negatively to cold/short days and positively to hot/long days), whereas men reacted significantly to sunshine-related changes (negatively to cloudy days and positively to sunny days). Subtle gender differences may thus underlie the pathophysiology of seasonal problems. Studies of an eventual efficacy of treating SAD women with raised ambient temperature, and gender-specific comparisons with other therapies, would be of interest.

  • 22.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Smedh, Kristina
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    A dual vulnerability hypothesis for seasonal depression is supported by the seasonal pattern assessment questionnaire in relation to the temperament and character inventory of personality in a general population.2004In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 82, no 1, 61-70 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Personality structure obtained from the psychobiological Temperament and Character Inventory (TCI) was studied in relation to self-reported seasonal variations in mood and behavior measured by the Seasonal Pattern Assessment Questionnaire (SPAQ). METHODS: The subjects comprised 1761 adults (57.6% women) in the age range 35-85 years, enrolled in the Betula prospective random cohort study of Umea, Sweden. RESULTS: Personality profiles of subjects who reported the occurrence of a high degree of seasonal variation as such were associated with a combination of high self-transcendence (ST) and high persistence (PS), irrespective of the level of harm avoidance (HA). Subjects who reported feeling worst in winter were associated with high HA, irrespective of the levels of ST and PS. Also, subjects feeling worst in summer or experiencing overall problems with seasonal variation were associated with high HA in their personality profiles. Using the SPAQ criteria to define seasonal affective disorder (SAD) or subsyndromal SAD (S-SAD), subjects with these disorders often had combinations of high self-transcendence (ST) and high persistence (PS), but with different associations with HA. LIMITATIONS: No evaluations were made for SAD or subsyndromal SAD according to the DSM-IV or ICD 10 criteria. CONCLUSIONS: Our results relating SPAQ with TCI give support for a dual vulnerability hypothesis for seasonal depression proposed in the literature, where it is attributed to a combination of a seasonal factor and a depression factor. Examining the literature regarding the relationships between the different TCI scales and monoamine neurotransmitter functions, those relationships suggest that these two vulnerability factors for seasonal depression may be modulated by different neurotransmitter systems.

  • 23. Chourbaji, Sabine
    et al.
    Brandwein, Christiane
    Gau, Daniel
    Depner, Martin
    Saam, Christina
    Johansson, Carolina
    Schalling, Martin
    Partonen, Timo
    Kasper, Siegfried
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Urani, Alexandre
    Lemberger, Thomas
    Schütz, Günther
    Schumann, Gunter
    Gass, Peter
    CREB-regulated diurnal activity patterns are not indicative for depression-like symptoms in mice and men.2008In: Medical Hypotheses, ISSN 0306-9877, E-ISSN 1532-2777, Vol. 70, no 1, 117-21 p.Article in journal (Refereed)
    Abstract [en]

    Activation of the transcription factor CREB by Ser142 phosphorylation is implicated in synchronizing circadian rhythmicity, which is disturbed in many depressive patients. Hence, one could assume that emotional behaviour and neuroendocrinological markers would be altered in CREB(S142A) mice, in which serine 142 is replaced by alanine, preventing phosphorylation at this residue. Moreover, associations of CREB Ser142 and seasonal affective disorder (SAD) might be detectable by the analysis of single-nucleotide polymorphisms (SNPs) in the CREB gene close to the Ser142 residue in SAD patients. However, neither CREB(S142A) mice demonstrate features of depression, nor there is evidence for an association of SAD with the CREB genotypes. Nevertheless, in humans there is an association of a global seasonality score and circadian rhythmicity with the CREB genotypes in healthy control probands, but not SAD patients. This parallels the phenotype of CREB(S142A) mice, presenting alterations of circadian rhythm and light-induced entrainment. Thus it is reasonable to assume that CREB Ser142 represents a molecular switch in mice and men, which is responsible for the (dys)regulation of circadian rhythms.

  • 24. de Frias, Cindy M
    et al.
    Annerbrink, Kristina
    Westberg, Lars
    Eriksson, Elias
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Catechol O-methyltransferase Val(158)Met polymorphism is associated with cognitive performance in nondemented adults2005In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 17, no 7, 1018-1025 p.Article in journal (Refereed)
    Abstract [en]

    The catechol O-methyltransferase ( COMT) gene is essential in the metabolic degradation of dopamine in the prefrontal cortex. In the present study, we examined the effect of a Val 158 Met polymorphism in the COMT gene on individual differences and changes in cognition ( executive functions and visuospatial ability) in adulthood and old age. The participants were 292 nondemented men ( initially aged 35-85 years) from a random sample of the population (i.e., the Betula study) tested at two occasions with a 5-year interval. Confirmatory factor analyses were used to test the underlying structure of three indicators of executive functions ( verbal fluency, working memory, and Tower of Hanoi). Associations between COMT, age, executive functioning, and visuospatial ( block design) tasks were examined using repeated-measures analyses of variance. Carriers of the Val allele ( with higher enzyme activity) compared with carriers of the Met/Met genotype ( with low enzyme activity) performed worse on executive functioning and visuospatial tasks. Individuals with the Val/Val genotype declined in executive functioning over the 5-year period, whereas carriers of the Met allele remained stable in performance. An Age x COMT interaction for visuospatial ability located the effect for middle-aged men only. This COMT polymorphism is a plausible candidate gene for executive functioning and fluid intelligence in nondemented middle-aged and older adults.

  • 25. de Frias, Cindy M
    et al.
    Annerbrink, Kristina
    Westberg, Lars
    Eriksson, Elias
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    COMT gene polymorphism is associated with declarative memory in adulthood and old age2004In: Behavior Genetics, ISSN 0001-8244, E-ISSN 1573-3297, Vol. 34, no 5, 533-539 p.Article in journal (Refereed)
    Abstract [en]

    Variation in memory performance is to a large extent explained by genes. In the prefrontal cortex, the catechol O-methyltransferase (COMT) gene is essential in the metabolic degradation of dopamine, a neurotransmitter implicated in cognitive functions. The present study examined the effect of a polymorphism in the COMT gene on individual differences and changes in memory in adulthood and old age. Tests assessing episodic and semantic memory were administered to 286 men (initially aged 35-85 years) from a random sample of the population (i.e., the Betula prospective cohort study) at two occasions followed over a 5-year period. Carriers of the Met/Met genotype (with low enzyme activity) performed better on episodic and semantic memory, as compared to carriers of the Val allele (with higher enzyme activity). Division of episodic memory into its recall and recognition components showed that the difference was specific to episodic recall, not recognition tasks; an effect that was observed across three age groups (middle-age, young-old, and old-old adults) and over a 5-year period. The COMT gene is a plausible candidate gene for memory functioning in adulthood and old age.

  • 26. de Frias, Cindy M
    et al.
    Bunce, David
    Wahlin, Åke
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Sleegers, Kristel
    Cruts, Marc
    Van Broeckhoven, Christine
    Nilsson, Lars-Göran
    Cholesterol and triglycerides moderate the effect of apolipoprotein E on memory functioning in older adults2007In: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 62, no 2, P112-P118 p.Article in journal (Refereed)
    Abstract [en]

    We used data from the Betula Study to examine associations between total cholesterol, triglycerides, and apolipoprotein E on 10-year changes in cognitive performance. Tests assessing episodic memory (recall and recognition), semantic memory (knowledge and fluency), and visuospatial ability (block design) were administered to 524 nondemented adults (initial age of 55-80 years); multilevel modeling was applied to the data. Higher triglyceride levels were associated with a decline in verbal knowledge. Lipid levels moderated the influence of apolipoprotein E on episodic memory, such that among epsilon 4 allele carriers, decline in recognition was noted for individuals with higher cholesterol levels. Cholesterol and triglyceride levels are pharmacologically modifiable risk factors that account for variation In normal cognitive aging.

  • 27. Dries, Daniel R.
    et al.
    Zhu, Yi
    Brooks, Mieu M.
    Forero, Diego A.
    Adachi, Megumi
    Cenik, Basar
    West, James M.
    Han, Yu-Hong
    Yu, Cong
    Arbella, Jennifer
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Del-Favero, Jurgen
    Lu, Q. Richard
    Callaerts, Patrick
    Birnbaum, Shari G.
    Yu, Gang
    Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior2016In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 22, 11647-11656 p.Article in journal (Refereed)
    Abstract [en]

    The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia. Here, we report that mice defective of the nicastrin subunit of gamma-secretase in oligodendrocytes have hypomyelination in the central nervous system. These mice have altered dopamine signaling and display profound abnormal phenotypes reminiscent of schizophrenia. In addition, we identify an association of the nicastrin gene with a human schizophrenia cohort. These observations implicate gamma-secretase and its mediated neurodevelopmental pathways in schizophrenia and provide support for the "myelination hypothesis" of the disease. Moreover, by showing that schizophrenia and obsessive-compulsive symptoms could be modeled in animals wherein a single genetic factor is altered, our work provides a biological basis that schizophrenia with obsessive-compulsive disorder is a distinct subtype of schizophrenia.

  • 28. Engström, C
    et al.
    Thornlund, A S
    Johansson, E L
    Långström, M
    Chotai, Jayanti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nylander, P O
    Anticipation in unipolar affective disorder.1995In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 35, no 1-2, 31-40 p.Article in journal (Refereed)
    Abstract [en]

    Anticipation describes an inheritance pattern within a pedigree with an increase in disease severity and/or decrease in age at onset in successive generations. The phenomenon of anticipation has recently been shown to be correlated with the expansion of trinucleotide repeat sequences in a neuromuscular disease, various neurodegenerative disorders and mental retardation. We have studied parent-offspring differences in age at onset and disease severity in 31 pairs with unilineal inheritance of unipolar affective disorder (UPAD). Life-table analyses showed a significant decrease in survival to 1st episode of major depression in the offspring generation compared with the parental generation (P = 0.0007). There was also a significant difference in age at onset (P < 0.001) between parents and offsprings. The offspring generation experienced onset 15.6 years earlier and illness 1.5 x more severe than did the parent generation. Furthermore, there was a significant correlation (P < 0.05) in age at onset between parent and offspring generations. When we excluded pairs where the affected parent has an age of onset greater than the age of the child at the time of ascertainment (i.e., 23 pairs left), there was still a significant (P = 0.02) decrease in age at onset (8.4 years) and 1.5 x more severe disease in the offspring generation. No evidence for specific maternal or paternal inheritance was found. We found evidence of anticipation in 75-80% of this sample of unilineal family pairs of UPAD. Anticipation is, thus, an inheritance pattern in a large group of UPAD which suggests that the expansion of trinucleotide repeat sequences is a possible mode of inheritance in this group of UPAD. The findings of anticipation in this study of families with UPAD and previous findings in families with BPAD suggest that the variable expression of unstable expansions of trinucleotide repeats may turn out to be the basis of the continuum of liability in affective disorders.

  • 29.
    Figueira, Joao
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Öhman, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls2016In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, no 8, 2562-2571 p.Article in journal (Refereed)
    Abstract [en]

    Saliva is a biofluid that is sensitive to metabolic changes and is straightforward to collect in a non-invasive manner, but it is seldom used for metabolite analysis when studying neurodegenerative disorders. We present a procedure for both an untargeted and targeted analysis of the saliva metabolome in which nuclear magnetic resonance (NMR) spectroscopy is used in combination with multivariate data analysis. The applicability of this approach is demonstrated on saliva samples selected from the 25 year prospective Betula study, including samples from dementia subjects with either Alzheimer's disease (AD) or vascular dementia at the time of sampling or who developed it by the next sampling/assessment occasion five years later, and age-, gender-, and education-matched control individuals without dementia. Statistically significant multivariate models were obtained that separated patients with dementia from controls and revealed seven discriminatory metabolites. Dementia patients showed significantly increased concentrations of acetic acid (fold change (fc) = 1.25, p = 2 x 10(-5)), histamine (fc = 1.26, p = 0.019), and propionate (fc = 1.35, p = 0.002), while significantly decreased levels were observed for dimethyl sulfone (fc = 0.81, p = 0.005), glycerol (fc = 0.79, p = 0.04), taurine (fc = 0.70, p = 0.007), and succinate (fc = 0.62, p = 0.008). Histamine, succinate, and taurine are known to be important in AD, and acetic acid and glycerol are involved in related pathways. Dimethyl sulfone and propionate originate from the diet and bacterial flora and might reflect poorer periodontal status in the dementia patients. For these seven metabolites, a weak but statistically significant pre-diagnostic value was observed. Taken together, we present a robust and general NMR analysis approach for studying the saliva metabolome that has potential use for screening and early detection of dementia.

  • 30. Forero, Diego A.
    et al.
    Herteleer, Liesbet
    De Zutter, Sonia
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Sunderby Hospital, Sweden.
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. Sunderby Hospital, Sweden.
    Callaerts, Patrick
    Del-Favero, Jurgen
    A network of synaptic genes associated with schizophrenia and bipolar disorder2016In: Schizophrenia Research, ISSN 0920-9964, E-ISSN 1573-2509, Vol. 17, no 1-3, 68-74 p.Article in journal (Refereed)
    Abstract [en]

    Identification of novel candidate genes for schizophrenia (SZ) and bipolar disorder (BP), two psychiatric disorders with large epidemiological impacts, is a key research area in neurosciences and psychiatric genetics. Previous evidence from genome-wide studies suggests an important role for genes involved in synaptic plasticity in the risk for SZ and BP. We used a convergent genomics approach, combining different lines of biological evidence, to identify genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A. These 7 genes were analyzed in a HapMap based association study comprising 48 common SNPs in 486 SZ, 351 BP patients and 514 control individuals recruited from an isolated population in Northern Sweden. Genetic analysis showed significant allelic associations of SNPs in PRKAR1A with SZ and of PPP3CB and PRKAR1A with BP. Our results highlight the feasibility and the importance of convergent genomic data analysis for the identification of candidate genes and our data provide support for the role of common inherited variants in synaptic genes and their involvement in the etiology of BP and SZ.

  • 31. Giddaluru, Sudheer
    et al.
    Espeseth, Thomas
    Salami, Alireza
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden.
    Westlye, Lars T
    Lundquist, Anders
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Christoforou, Andrea
    Cichon, Sven
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Steen, Vidar M
    Reinvang, Ivar
    Nilsson, Lars Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). ARC, Karolinska Institutet, Stockholm, Sweden.
    Le Hellard, Stéphanie
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Genetics of structural connectivity and information processing in the brain2016In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, no 9, 4643-4661 p.Article in journal (Refereed)
    Abstract [en]

    Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.

  • 32. Hardy, J
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Alafuzoff, I
    Bucht, G
    Marcusson, J
    Nyberg, P
    Perdahl, E
    Wester, P
    Winblad, B
    Transmitter deficits in Alzheimer's disease.1985In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 7, no 4, 545-63 p.Article in journal (Refereed)
    Abstract [en]

    The pattern of neurotransmitter pathway losses in Alzheimer's disease are reviewed. Deficits of the cholinergic pathway from the nucleus basalis, the noradrenergic pathway from the locus coeruleus and the serotoninergic pathway from the raphe nuclei are established. Cortical somatostatin interneurons are affected and dopaminergic neurons may be affected although these may be late or secondary phenomena in the disease process. Other neuronal systems, particularly in the hippocampus and temporal cortex, are also damaged. However, the disease is not one of generalised neuronal atrophy since some neurons are selectively spared. The established pathway-specific losses are discussed in relation to the clinical symptomatology and the pathology of the disorder. The biochemical and histological findings are compared with similar measurements made on tissues from other dementing disorders in an attempt to trace features common to dementias. Finally, as an addendum, a hypothesis is briefly outlined which attempts to explain the common features of the affected neurons and the pathogenesis of the disorder.

  • 33.
    Hägg, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lindblom, Yvonne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Mjörndal, Tom
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    High prevalence of the metabolic syndrome among a Swedish cohort of patients with schizophrenia2006In: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 21, no 2, 93-98 p.Article in journal (Refereed)
    Abstract [en]

    Several cardiovascular risk factors have been linked to antipsychotic treatment and cardiovascular mortality is increased in these patients compared to the general population. The full metabolic syndrome (or its components) is associated with an increased risk of cardiovascular disorders. The prevalence of the metabolic syndrome was investigated using a cross-sectional study design in a cohort of 269 patients, aged 20-69 years, with schizophrenia living in Northern Sweden, and was defined according to the criteria of the National Cholesterol Education program. The prevalence of the metabolic syndrome was 34.6% (95% CI = 28.8-40.3) and highest (43%; 95% CI = 32-53) for participants aged 40-49 years. Clozapine treated subjects reached the highest prevalence of the metabolic syndrome (48%; 95% CI = 34-62). The prevalence was similar for men (32.8%; 95% CI = 25.8-39.8) and women (38.0%; 95% CI = 27.9-48.2). Men had a high prevalence of hypertension (49.2%; 95% CI = 41.7-56.6) and women had high prevalence of low high-density lipoprotein cholesterol (40.2%; 95% CI = 30.0-50.4) and abdominal obesity (75.0%; 95% CI = 66.0-84.0). Subjects with the metabolic syndrome had significantly higher mean body mass index (BMI) (P < 0.001), HbA1c (P = 0.002), and fasting serum insulin (P < 0.001) compared to non-metabolic syndrome subject. Subjects with the metabolic syndrome had also significantly more often a positive history of cardiovascular diseases compared to non-metabolic syndrome subjects (25.8% versus 12.5%; P = 0.01). Of all study subjects 36.8% were obese (BMI > 30). These results clearly show that the metabolic syndrome and its components are highly prevalent in patients with schizophrenia. Physicians treating patients with schizophrenia are recommended to monitor the components included in the metabolic syndrome.

  • 34.
    Karling, P
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Danielsson, Å
    Pettersson, M
    Söderström, I
    Del-Favero, J
    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.
    The val158met Catechol-O-methyl-transferase (COMT) polymorphism is associated with irritable bowel syndrome-like symptomsManuscript (Other academic)
  • 35.
    Karling, Pontus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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.
    No difference in symptoms of irritable bowel syndrome between healthy subjects and patients with recurrent depression in remission2007In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 19, no 11, 896-904 p.Article in journal (Refereed)
    Abstract [en]

    There is bidirectional comorbidity between anxiety/depression and irritable bowel syndrome (IBS). To investigate the prevalence of IBS symptoms, and factors associated with gastrointestinal symptoms in patients with recurrent depressive disorder. Patients (n = 95) with recurrent type of major depression according to DSM-IV criteria and sex- and age-matched controls (n = 190) were sent questionnaires investigating symptoms of IBS [Gastrointestinal Symptom Rating Scale (GSRS)-IBS] and symptoms of anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Medical records were checked over a 10-year period for chronic somatic symptoms or diseases. Seventy-three patients with unipolar disorder (mean age 63.6 years SD 13.8; range 23–86 years) and 156 controls (mean age 59.2 years SD 11.6, range 21–85 years) responded. Patients with recurrent depression had higher GSRS-IBS scores and showed a strong correlation between symptoms of IBS and anxiety-depression (rs = 0.54; P < 0.001). IBS symptoms were also associated with multiple pain symptoms, higher health-seeking behaviour and selective-serotonin-reuptake inhibitor intake. However, patients with recurrent depression (n = 46) in remission (HADS-Depression score <8) did not have more symptoms of IBS than controls (GSRS-IBS median score 6.0 vs 6.5; P = 0.46). There is a strong association between symptoms of IBS and symptoms of anxiety and depression, whereas depressive patients in remission do not have more IBS symptoms than controls.

  • 36.
    Karling, Pontus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wikgren, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Söderström, Ingegerd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Del-Favero, Jurgen
    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.
    The relationship between the val158met catechol-o-methyltransferase (COMT) polymorphism and irritable bowel syndrome.2011In: PloS one, ISSN 1932-6203, Vol. 6, no 3, e18035- p.Article in journal (Refereed)
    Abstract [en]

    Background

    The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS.

    Methodology/Principal Findings

    867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary.

    Results

    There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi2 (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi2 (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi2 (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi2 (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi2 (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi2 (1) 3.0; p = 0.08).

    Conclusions/Significance

    In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients.

  • 37.
    Karling, Pontus
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Danielsson, Åke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Medicin.
    Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals.2007In: Scand J Gastroenterol, ISSN 0036-5521, Vol. 42, no 11, 1294-1301 p.Article in journal (Refereed)
  • 38. Karlsson, Thomas
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Börjesson, Arne
    Nilsson, Lars-Göran
    Primed word-fragment completion and successive memory test performance in normal aging.2003In: Scandinavian Journal of Psychology, ISSN 0036-5564, E-ISSN 1467-9450, Vol. 44, no 4, 355-61 p.Article in journal (Refereed)
    Abstract [en]

    Young and old subjects were investigated to examine whether: the effects of priming are influenced by aging; there is independence between primed word-fragment completion and recognition performances; and the dependence between different tests is influenced by aging. A successive test paradigm was employed involving repeated assessment of to-be-remembered words by means of recognition and primed word-fragment completion. The results show that implicit memory declines with increasing age, and that correlations between different memory tests decrease with age. The outcome suggests that age-related memory decline involves several forms of memory, including primed word-fragment completion, and is reflected in correlations between measures of implicit and explicit memory.

  • 39.
    Katarina, Nordfjäll
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Svenson, Ulrika
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Roos, Göran
    The paternal influence on telomere length is stronger than the maternal and the heritable impact diminishes with ageManuscript (Other academic)
  • 40.
    Katarina, Nordfjäll
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Ulrika, Svenson
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lenner, Per
    Roos, Göran
    Human blood cell telomere attrition rate is telomere length dependent but not associated to tumour development.Manuscript (Other academic)
  • 41.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Nilsson, Lars-Göran
    Stockholm University.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Elias
    Gothenburg University.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Decreased medial temporal lobe activation in BDNF 66Met allele carriers during memory encoding2013In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 51, no 12, 2462-2468 p.Article in journal (Refereed)
    Abstract [en]

    The Met allele of the Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism has been associated with impaired activity-dependent secretion of BDNF protein and decreased memory performance. Results from imaging studies relating Val(66)Met to brain activation during memory processing have been inconsistent, with reports of both increased and decreased activation in the Medial Temporal Lobe (MTL) in Met carriers relative to Val homozygotes. Here, we extensively studied BDNF Val(66)Met in relation to brain activation and white matter integrity as well as memory performance in a large imaging (n=194) and behavioral (n=2229) sample, respectively. Functional magnetic resonance imaging (fMRI) was used to investigate MTL activation in healthy participants in the age of 55-75 years during a face-name episodic encoding and retrieval task. White matter integrity was measured using diffusion tensor imaging.

    BDNF Met allele carriers had significantly decreased activation in the MTL during encoding processes, but not during retrieval processes. In contrast to previous proposals, the effect was not modulated by age and the polymorphism was not related to white matter integrity. Met carriers had lower memory performance than Val homozygotes, but differences were subtle and not significant. In conclusion, the BDNF Met allele has a negative influence on MTL functioning, preferentially during encoding processes, which might translate into impaired episodic memory function.

  • 42.
    Lind, Johanna
    et al.
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N-8, S-171 76 Stockholm, Sweden.
    Larsson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Persson, Jonas
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Ingvar, Martin
    Department of Clinical Neuroscience, MR Research Center, Karolinska Hospital N-8, S-171 76 Stockholm, Sweden.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, S-106 91 Stockholm, Sweden.
    Bäckman, Lars
    National Centre of Aging, Box 6401, S-113 82 Stockholm, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Cruts, Marc
    Department of Molecular Genetics, Flanders Interuniversity, Institute of Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium.
    Sleegers, Kristel
    Department of Molecular Genetics VIB8, University of Antwerp, Campus CDE, Universiteitsplein 1, B-2610 Antwerp, Belgium.
    Van Broeckhoven, Christine
    Department of Molecular Genetics, Flanders Interuniversity, Institute of Biotechnology, University of Antwerp, B-2610 Antwerpen, Belgium.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4: Relation to chronological age and recognition memory2006In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 396, no 1, 23-27 p.Article in journal (Refereed)
    Abstract [en]

    Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.

  • 43. Lindholm, E
    et al.
    Ekholm, B
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Balciuniene, J
    Johansson, G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Castensson, A
    Koisti, M
    Nylander, P O
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Pettersson, U
    Adolfsson, R
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jazin, E
    Linkage analysis of a Swedish kindred provides further support for a susceptibility locus for schizophrenia on chromosome 6p231999In: American Journal of Medical Genetics, ISSN 0148-7299, E-ISSN 1096-8628, Vol. 88, no 4, 369-377 p.Article in journal (Refereed)
    Abstract [en]

    Several reports have indicated genetic linkage between markers on the short arm of chromosome 6 and schizophrenia. However, significant threshold levels were not always achieved, and the chromosomal regions identified are large and different in different families. One way to decrease the problem of heterogeneity is to study a single extended pedigree. Here we report the analysis of a very large, previously undescribed pedigree from northern Sweden that includes 31 affected individuals. We typed 16 markers spanning 40 cM on the short arm of chromosome 6. Linkage analysis was performed only with the affected individuals. Suggestive lod scores (maximum 2.6) were obtained with markers on chromosome 6p23 in a single branch of the large pedigree indicating possible heterogeneity inside the family. A haplotype comprising markers from D6S309 to D6S1578 was found to segregate with the disease. This chromosomal region is included within a segment proposed to contain a susceptibility gene for schizophrenia by many other investigators. Our results thus give further support for a possible localization of a susceptibility locus for schizophrenia in 6p23 and help to narrow the candidate chromosomal region to the segment included between markers D6S309 and D6S1578. Copyright 1999 Wiley-Liss, Inc.

  • 44. Lindholm, E
    et al.
    Ekholm, B
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Shaw, S
    Jalonen, P
    Johansson, G
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Pettersson, U
    Sherrington, R
    Adolfsson, R
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jazin, E
    A schizophrenia-susceptibility locus at 6q25, in one of the world´s largest reported pedigree2001In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 69, no 1, 96-105 p.Article in journal (Refereed)
    Abstract [en]

    We have completed a genome scan of a 12-generation, 3,400-member pedigree with schizophrenia. Samples from 210 individuals were collected from the pedigree. We performed an "affecteds-only" genome-scan analysis using 43 members of the pedigree. The affected individuals included 29 patients with schizophrenia, 10 with schizoaffective disorders, and 4 with psychosis not otherwise specified. Two sets of white-European allele frequencies were used-one from a Swedish control population (46 unrelated individuals) and one from the pedigree (210 individuals). All analyses pointed to the same region: D6S264, located at 6q25.2, showed a maximum LOD score of 3.45 when allele frequencies in the Swedish control population were used, compared with a maximum LOD score of 2.59 when the pedigree's allele frequencies were used. We analyzed additional markers in the 6q25 region and found a maximum LOD score of 6.6 with marker D6S253, as well as a 6-cM haplotype (markers D6S253-D6S264) that segregated, after 12 generations, with the majority of the affected individuals. Multipoint analysis was performed with the markers in the 6q25 region, and a maximum LOD score of 7.7 was obtained. To evaluate the significance of the genome scan, we simulated the complete analysis under the assumption of no linkage. The results showed that a LOD score >2.2 should be considered as suggestive of linkage, whereas a LOD score >3.7 should be considered as significant. These results suggest that a common ancestral region was inherited by the affected individuals in this large pedigree.

  • 45. Lindholm, Eva
    et al.
    Åberg, Karolina
    Ekholm, Birgit
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Pettersson, Ulf
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jazin, Elena E
    Reconstruction of ancestral haplotypes in a 12-generation schizophrenia pedigree2004In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 14, no 1, 1-8 p.Article in journal (Refereed)
    Abstract [en]

    We searched for candidate chromosomal regions inherited identical by descent in 19 patients suffering from schizophrenia or schizoaffective disorder that are related 12 generations back, to an ancestral couple born in the middle of the seventeenth century. To accomplish this goal, we constructed complete chromosomal haplotypes for each patient using genotype data from 450 markers. In total, 12 haplotype regions (with sizes ranging from 0.6 to 10.9 cM) constituted by three markers each were identical in three or more of the affected individuals. The largest genomic segment was located on 6q25, a region previously shown to be significantly more frequent in patients than controls, and proposed to contain a schizophrenia susceptibility locus. For the remaining 11 candidate haplotypes, we estimated haplotype frequencies from all the 43 affected members collected from the same family and 46 unrelated control individuals. This analysis indicated that at least four of the 11 candidate haplotypes are ancestral, since the frequencies were significantly higher in patients than in controls. Five additional haplotypes showed higher estimated frequencies in the patients but the differences were not significant. Interestingly, five of these 11 genomic regions are located in, or close to, candidate regions previously suggested to contain susceptibility genes for schizophrenia. The regions are 5q21-23, 8p21-22, 1 0p13-15, 13q12-13 and 22q12-13. Several of these haplotypes are probably ancestral linkage disequilibrium blocks inherited from the original couple. There exists, however, the possibility that one or more of these regions harbour schizophrenia susceptibility loci that may have epistatic interactions among them.

  • 46.
    Lundberg, Mattias
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Perris, Carlo
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Schlette, Paul
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Transhistorical variations in personality and their association with experiences of parental rearing.1999In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 14, no 6, 303-18 p.Article in journal (Refereed)
    Abstract [en]

    A population sample comprised of 765 subjects (367 males and 398 females), in the age range of 15-81 years, completed the EMBU, a reliable questionnaire aimed at assessing experiences of parental rearing, and the TCI, a self-report questionnaire aimed at assessing dimensions of temperament and character. The study had three main aims: 1) to verify, on a larger scale, previous findings suggesting the occurrence of significant associations between experiences of parental rearing and aspects of temperament and character, 2) to assess possible variations in temperament and character in cohorts of subjects who have grown up in different historical epochs, and 3) to investigate to what extent transgenerational differences in parental rearing are detectable in different associations with various dimensions of personality. Several, albeit small, significant and meaningful associations between experiences of parental rearing and both temperament and character dimensions have been found, adding support to the robustness of previously reported results obtained in an independent smaller series. Also, several significant differences among subjects in different age groups have been found, both concerning temperament variables and character dimensions. Finally, the results show that associations between experiences of parental rearing and dimensions of temperament and character are most pronounced in subjects belonging to the youngest cohort and almost nil in the cohort comprising the oldest subjects.

  • 47.
    Maitland, Scott B
    et al.
    Family Relations and Applied Nutrition, University of Guelph, ON, Canada .
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bäckman, Lars
    Aging Research Center, Karolinska Institute, Stockholm, Sweden.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Sweden.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    On the structure of personality: are there separate temperament and character factors?2009In: Personality and Individual Differences, ISSN 0191-8869, E-ISSN 1873-3549, Vol. 47, no 3, 180-184 p.Article in journal (Refereed)
    Abstract [en]

    The Temperament and Character Inventory (TCI) is a widely used measure of psychobiological aspects of personality. Theoretically, the TCI is defined as comprising four temperament and three character factors. Most previous examinations of the factor structure have used exploratory factor methods with mixed results. We used confirmatory factor analyses (CFA) to examine the TCI in a sample of 2423 adults aged 35–90 years (1093 women, 1330 men) from the Betula study. Support for the seven TCI factors was mixed. Models including second-order factors provided no evidence that the seven first-order TCI factors reflect higher-order temperament and character constructs. Our findings provide no support that individual differences on the seven first-order TCI factors reflect distinct temperament or character dimensions of personality. Whereas more complex modeling strategies rejected separate character and temperament models, the simultaneous (seven-factor) model, and the use of second-order factors; the harm avoidance, self-directedness, and cooperativeness factors were acceptable examined individually. Results for novelty seeking were marginal and self-transcendence, reward dependence and/or persistence factors were not acceptable.

  • 48. Malm, J
    et al.
    Kristensen, B
    Ekstedt, J
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wester, P
    CSF monoamine metabolites, cholinesterases and lactate in the adult hydrocephalus syndrome (normal pressure hydrocephalus) related to CSF hydrodynamic parameters.1991In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 54, no 3, 252-9 p.Article in journal (Refereed)
    Abstract [en]

    Monoamine metabolites, cholinesterases and lactic acid in lumbar cerebrospinal fluid (CSF) were investigated on patients with the adult hydrocephalus syndrome (idiopathic normal pressure syndrome; AHS, n = 15), Alzheimer's disease (AD, n = 14), multi-infarct dementia (MID, n = 13) and controls (n = 21). Patients had clinical and CSF hydrodynamic investigations. Monoamine concentrations were determined by reversed-phase liquid chromatography, cholinesterases and lactate were determined photometrically. In the AHS patients, CSF monoamine concentrations were not significantly different compared with controls, AD or MID patients. AHS and AD patients showed a similar reduction of CSF acetylcholinesterase activity compared with controls. Positive correlations were found in concentrations of CSF homovanillic acid, CSF 5-hydroxyindoleacetic acid and CSF lactic acid versus CSF outflow conductance (that is, resistance against CSF outflow) in the AHS patients. A similar pattern was observed in a subgroup of MID patients characterised by dilated ventricles and disturbed CSF hydrodynamics. These data suggest that a low CSF outflow conductance may facilitate the clearance of acidic substances from the arachnoid space at the probenecid sensitive active transport site. Alternative explanations would be that a pathologically low CSF outflow conductance is accompanied by an inverse caudorostral flow of CSF or a compromised trans-ependymal diffusion.

  • 49.
    Maripuu, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wikgren, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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.
    Bipolar patients at risk for developing hypocortisolism: Long-term lithium treatment is preventiveManuscript (preprint) (Other academic)
  • 50.
    Maripuu, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wikgren, Mikael
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    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.
    Relative hypocortisolism is associated with obesity and the metabolic syndrome in recurrent affective disordersManuscript (preprint) (Other academic)
12 1 - 50 of 83
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