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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, p. 636-7Article 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, p. 3962, 3967-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, p. 4098-9Article 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, p. 2586, 2590-1Article in journal (Refereed)
  • 6.
    Adolfsson, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Linge, E
    [Cognitive psychotherapy in the elderly with anxiety depressive disorders is effective]1992In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 89, no 5, p. 291-4Article in journal (Refereed)
  • 7.
    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, p. 491-Article in journal (Refereed)
  • 8.
    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, p. 828-837Article 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

  • 9.
    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, p. 585-592Article 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.

  • 10.
    Alaerts, Maaike
    et al.
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Venken, Tine
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Lenaerts, An-Sofie
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    De Zutter, Sonia
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    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.
    Del-Favero, Jurgen
    Applied Molecular Genomics Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Antwerp (UA), Belgium.
    Lack of association of an insertion/deletion polymorphism in the G protein-coupled receptor 50 with bipolar disorder in a Northern Swedish population2006In: Psychiatric Genetics, ISSN 0955-8829, E-ISSN 1473-5873, Vol. 16, no 6, p. 235-236Article in journal (Refereed)
    Abstract [en]

    GPR50 is a G protein-coupled receptor, located on Xq28 and related to the melatonin receptor family. It is suggested as a functional and positional candidate gene for bipolar disorder (BP). Recently an insertion/deletion polymorphism in GPR50, Delta502-505, was found to be associated with BP in a Scottish association sample (P=0.007). When the analysis was restricted to female subjects, the association increased in significance (P=0.00023). We attempted to replicate this finding in a Northern Swedish association sample, but no significant association was detected (P=0.7, women only: P=0.65).

  • 11. 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, p. 61-72Article 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.

  • 12. 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, p. 209-25Article 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.

  • 13. 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, p. 531-4Article 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.

  • 14.
    Andersson, John
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Oudin, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordin, Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Road traffic noise, air pollution, and risk of dementia: results from the Betula project2018In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 166, p. 334-339Article in journal (Refereed)
    Abstract [en]

    Background: There is growing evidence for a negative impact of traffic-related air pollution on risk of dementia. However, the contribution of noise exposure to this association has been rarely examined.

    Objective: We aimed to investigate the individual and combined effect of noise and air pollution on risk of dementia.

    Methods: Data on dementia incidence over a 15 year period was obtained from the Betula project, a longitudinal study on health and ageing. Estimates of annual mean levels of nitrogen oxides (NOx) at the participants’ residential address were obtained using a land-use regression model. Modelled data provided road traffic noise levels (Leq. 24 h) at the participants’ residential address at baseline. Cox proportional hazard regression was used to calculate hazard ratios (HR).

    Results: Of 1721 participants at baseline, 302 developed dementia during the follow up period. Exposure to noise levels (Leq. 24 h) > 55 dB had no significant effect on dementia risk (HR 0.95; CI: 0.57, 1.57). Residing in the two highest quartiles of NOx exposure was associated with an increased risk of dementia. The risk associated with NOx was not modified by adjusting for noise. Moreover, we found no significant interaction effects between NOx and road traffic noise on dementia risk.

    Conclusion: We found no evidence that exposure to road traffic noise, either independently or in combination with traffic air pollution, was associated with risk of dementia in our study area. Our results suggest that pollution should be considered the main component in the association between traffic related exposures and dementia.

  • 15. Angst, Jules
    et al.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Benazzi, Franco
    Gamma, Alex
    Hantouche, Elie
    Meyer, Thomas D
    Skeppar, Peter
    Vieta, Eduard
    Scott, Jan
    The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients2005In: Journal of Affective Disorders, ISSN 0165-0327, E-ISSN 1573-2517, Vol. 88, no 2, p. 217-233Article in journal (Refereed)
    Abstract [en]

    Background: Bipolar disorders (BP) are frequently diagnosed and treated as pure depression initially; accurate diagnosis often being delayed by 8 to 10 years. In prospective studies, the presence of hypomanic symptoms in adolescence is strongly predictive of later bipolar disorders. As such, an instrument for self-assessment of hypomanic symptoms might increase the detection of suspected and of manifest, but under-treated, cases of bipolar disorders.

    Methods: The multi-lingual hypomania checklist (HCL-32) has been developed and is being tested internationally. This preliminary paper reports the performance of the scale in distinguishing individuals with BP (N=266) from those with major depressive disorder (MDD; N= 160). The samples were adult psychiatry patients recruited in Italy (N= 186) and Sweden (N=240).

    Results: The samples reported similar clinical profiles and the structure for the HCL-32 demonstrated two main factors identified as "active/elated" hypomania and "risk-taking/irritable" hypomania. The HCL-32 distinguished between BP and MDD with a sensitivity of 80% and a specificity of 51%.

    Limitations: Although the HCL-32 is a sensitive instrument for hypomanic symptoms, it does not distinguish between BP-1 and BP-11 disorders.

    Conclusions: Future studies should test if different combinations of items. possibly recording the consequences of hypomania, can distinguish between these BP subtypes.

  • 16. Angst, Jules
    et al.
    Meyer, Thomas D
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Skeppar, Peter
    Carta, Mauro
    Benazzi, Franco
    Lu, Ru-Band
    Wu, Yi-Hsuan
    Yang, Hai-Chen
    Yuan, Cheng-Mei
    Morselli, Paolo
    Brieger, Peter
    Katzmann, Judith
    Teixeira Leão, Ines Alice
    Del Porto, José Alberto
    Hupfeld Moreno, Doris
    Moreno, Ricardo A
    Soares, Odeilton T
    Vieta, Eduard
    Gamma, Alex
    Hypomania: a transcultural perspective2010In: World Psychiatry, ISSN 1723-8617, E-ISSN 2051-5545, Vol. 9, no 1, p. 41-49Article in journal (Refereed)
    Abstract [en]

    This study examined the transcultural robustness of a screening instrument for hypomania, the Hypomania Checklist-32, first revised version (HCL-32 R1). It was carried out in 2606 patients from twelve countries in five geographic regions (Northern, Southern and Eastern Europe, South America and East Asia). In addition, GAMIAN Europe contributed data from its members. Exploratory and confirmatory factor analyses were used to examine the transregional stability of the measurement properties of the HCL-32 R1, including the influence of sex and age as covariates. Across cultures, a two-factor structure was confirmed: the first factor (F1) reflected the more positive aspects of hypomania (being more active, elated, self-confident, and cogni-tively enhanced); the second factor (F2) reflected the more negative aspects (being irritable, impulsive, careless, more substance use). The measurement properties of the HCL-32 R1 were largely invariant across cultures. Only few items showed transcultural differences in their relation to hypomania as measured by the test. F2 was higher among men and in more severe manic syndromes; F1 was highest in North and East Europe and lowest in South America. The scores decreased slightly with age. The frequency of the 32 items showed remarkable similarities across geographic areas, with two excep-tions: South Europeans had lower symptom frequencies in general and East Europeans higher rates of substance use. These findings support the interna-tional applicability of the HCL-32 R1 as a screening instrument for hypomania.

  • 17. 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, p. 94-9Article 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.

  • 18. Athanasiu, Lavinia
    et al.
    Giddaluru, Sudheer
    Fernandes, Carla
    Christoforou, Andrea
    Reinvang, Ivar
    Lundervold, Astri J.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, Elias
    Sundet, Kjetil
    Djurovic, Srdjan
    Espeseth, Thomas
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Steen, Vidar M.
    Andreassen, Ole A.
    Le Hellard, Stephanie
    A genetic association study of CSMD1 and CSMD2 with cognitive function2017In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 61, p. 209-216Article in journal (Refereed)
    Abstract [en]

    The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease.

  • 19. Bajbouj, Malek
    et al.
    Merkl, Angela
    Schlaepfer, Thomas E
    Frick, Caroline
    Zobel, Astrid
    Maier, Wolfgang
    O'Keane, Veronica
    Corcoran, Ciaran
    Adolfsson, Rolf
    University Hospital Umeå, Umeå, Sweden.
    Trimble, Michael
    Rau, Harald
    Hoff, Hans-Joachim
    Padberg, Frank
    Müller-Siecheneder, Florian
    Audenaert, Kurt
    van den Abbeele, Dirk
    Matthews, Keith
    Christmas, David
    Eljamel, Sam
    Heuser, Isabella
    Two-year outcome of vagus nerve stimulation in treatment-resistant depression2010In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 30, no 3, p. 273-281Article in journal (Refereed)
    Abstract [en]

    One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms. Some of the previous studies of vagus nerve stimulation (VNS) have suggested antidepressant effects. Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model repeated-measures analysis of variance revealed a significant reduction (P < or = 0.05) at all the 3 time points in the 28-item Hamilton Rating Scale for Depression (HRSD28) score, the primary outcome measure. After 2 years, 53.1% (26/49) of the patients fulfilled the response criteria (> or =50% reduction in the HRSD28 scores from baseline) and 38.9% (19/49) fulfilled the remission criteria (HRSD28 scores < or = 10). The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough, and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no other deaths were reported. No statistically significant differences were seen in the number of concomitant antidepressant medications. The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression.

  • 20. Bergman, Olle
    et al.
    Westberg, Lars
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, Elias
    Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia2010In: Progress in Neuro-psychopharmacology and Biological Psychiatry, ISSN 0278-5846, E-ISSN 1878-4216, Vol. 34, no 6, p. 1094-1097Article in journal (Refereed)
    Abstract [en]

    The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented.

  • 21.
    Boraxbekk, Carl-Johan
    et al.
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Lundquist, Anders
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Nilsson, Lars-Göran
    Aging Research Center, Karolinska Institutet.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Free Recall Episodic Memory Performance Predicts Dementia 10 Years Prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study2015In: Dementia and geriatric cognitive disorders extra, E-ISSN 1664-5464, Vol. 5, no 2, p. 191-202Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Methods: Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Results: Age-and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. Conclusion: The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.

  • 22. 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, p. 122-8Article 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.

  • 23. 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, p. 78-85Article 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.

  • 24. 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, article id 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.

  • 25. Ceulemans, Shana
    et al.
    De Zutter, Sonia
    Heyrman, Lien
    Norrback, Karl-Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordin, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Goran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Del-Favero, Jurgen
    Claes, Stephan
    Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population2011In: Bipolar Disorders, ISSN 1398-5647, E-ISSN 1399-5618, Vol. 13, no 7-8, p. 614-623Article in journal (Refereed)
    Abstract [en]

    Objectives: Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most consistent findings in the pathophysiology of mood disorders. The potential role of genes related to HPA axis function has been investigated extensively in major depression. However, in bipolar disorder (BPD) such studies are scarce. We performed a systematic HapMap-based association study of six genes crucial for HPA axis function in relation to BPD.

    Methods: Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected in order to identify all haplotypes with a frequency of more than 1% in the genes encoding the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotrophin releasing hormone receptor 1 (CRH-R1) and 2 (CRH-R2), CRH binding protein (CRH-BP), and FK binding protein 5 (FKBP5). This resulted in a total selection of 225 SNPs that were genotyped and analyzed in 309 BPD patients and 364 matched control individuals all originating from an isolated northern Swedish population.

    Results: Consistent evidence for an association with BPD was found for NR3C1, the gene encoding GR. Almost all SNPs in two adjacent haplotype blocks contributed to the positive signal, comprised of significant single marker, sliding window, and haplotype-specific p-values. All these results point to a moderately frequent (10-15%) susceptibility haplotype covering the entire coding region and 3 > untranslated region (UTR) of NR3C1.

    Conclusions: This study contributes to the growing evidence for a role of the glucocorticoid receptor gene (NR3C1) in vulnerability to mood disorders, and BPD in particular, and warrants further in vitro investigation of the at-risk haplotypes with respect to disease etiology. However, this association might be restricted to this specific population, as it is observed in a rather small sample from an isolated population without replication, and data from large meta-analyses for genome-wide association studies in BPD do not show the GR as a very strong candidate.

  • 26.
    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, p. 130-4Article 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.

  • 27.
    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, p. 181-6Article 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.

  • 28.
    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, p. 19-26Article 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.

  • 29.
    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, p. 251-9Article in journal (Refereed)
  • 30.
    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, p. 45-54Article 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.

  • 31.
    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, p. 429-37Article 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.

  • 32.
    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, p. 61-70Article 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.

  • 33. 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, p. 117-21Article 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.

  • 34. Crowley, James
    et al.
    Mudgal, Poorva
    Nordin Adolfsson, Annelie
    Umeå University.
    Åberg, Karolina
    Alaerts, Maaike
    Genovese, Giulio
    McCarroll, Steven
    Del-Favero, Jurgen
    Adolfsson, Rolf
    Umeå University.
    Sullivan, Patrick
    The genomics of bipolar and schizophrenic disorders in a large pedigree from a northern Swedish isolate2019In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 29, p. S902-S903Article in journal (Other academic)
  • 35. 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, p. 1018-1025Article 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.

  • 36. 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, p. 533-539Article 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.

  • 37. 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, p. P112-P118Article 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.

  • 38. de Jong, Simone
    et al.
    Abdalla Diniz, Mateus Jose
    Saloma, Andiara
    Gadelha, Ary
    Santoro, Marcos L.
    Ota, Vanessa K.
    Noto, Cristiano
    Curtis, Charlesg
    Newhouse, Stephen J.
    Patel, Hamel
    Hall, Lynsey S.
    O'Reilly, Paul F.
    Belangero, Sintia, I
    Bressan, Rodrigo A.
    Breen, Gerome
    Wray, Naomi R.
    Ripke, Stephan
    Mattheisen, Manuel
    Trzaskowski, Maciej
    Byrne, Enda M.
    Abdellaoui, Abdel
    Adams, Mark J.
    Agerbo, Esben
    Air, Tracy M.
    Andlauer, Till F. M.
    Bacanu, Silviu-Alin
    Baekvad-Hansen, Marie
    Beekman, Aartjan T. F.
    Bigdeli, Tim B.
    Binder, Elisabeth B.
    Blackwood, Douglas H. R.
    Bryois, Julien
    Buttenschon, Henriette N.
    Bybjerg-Grauholm, Jonas
    Cai, Na
    Castelao, Enrique
    Christensen, Jane Hvarregaard
    Clarke, Toni-Kim
    Coleman, Jonathan R., I
    Colodro-Conde, Lucia
    Couvy-Duchesne, Baptiste
    Craddock, Nick
    Crawford, Gregory E.
    Davies, Gail
    Deary, Ian J.
    Degenhardt, Franziska
    Derks, Eske M.
    Direk, Nese
    Dolan, Conor, V
    Dunn, Erin C.
    Eley, Thalia C.
    Escott-Price, Valentina
    Kiadeh, Farnush Farhadi Hassan
    Finucane, Hilary K.
    Forstner, Andreas J.
    Frank, Josef
    Gaspar, Helena A.
    Gill, Michael
    Goes, Fernando S.
    Gordon, Scott D.
    Grove, Jakob
    Hansen, Christine Soholm
    Hansen, Thomas F.
    Herms, Stefan
    Hickie, Ian B.
    Hoffmann, Per
    Homuth, Georg
    Horn, Carsten
    Hottenga, Jouke-Jan
    Hougaard, David M.
    Ising, Marcus
    Jansen, Rick
    Jones, Ian
    Jones, Lisa A.
    Jorgenson, Eric
    Knowles, James A.
    Kohane, Isaac S.
    Kraft, Julia
    Kretzschmar, Warren W.
    Krogh, Jesper
    Kutalik, Zoltan
    Li, Yihan
    Lind, Penelope A.
    MacIntyre, Donald J.
    MacKinnon, Dean F.
    Maier, Robert M.
    Maier, Wolfgang
    Marchini, Jonathan
    Mbarek, Hamdi
    Mcgrath, Patrick
    Mcguffin, Peter
    Medland, Sarah E.
    Mehta, Divya
    Middeldorp, Christel M.
    Mihailov, Evelin
    Milaneschi, Yuri
    Milani, Lili
    Mondimore, Francis M.
    Montgomery, Grant W.
    Mostafavi, Sara
    Mullins, Niamh
    Nauck, Matthias
    Ng, Bernard
    Nivard, Michel G.
    Nyholt, Dale R.
    Oskarsson, Hogni
    Owen, Michael J.
    Painter, Jodie N.
    Pedersen, Carsten Bocker
    Pedersen, Marianne Giortz
    Peterson, Roseann E.
    Pettersson, Erik
    Peyrot, Wouter J.
    Pistis, Giorgio
    Posthuma, Danielle
    Quiroz, Jorge A.
    Qvist, Per
    Rice, John P.
    Riley, Brien P.
    Rivera, Margarita
    Mirza, Saira Saeed
    Schoevers, Robert
    Schulte, Eva C.
    Shen, Ling
    Shyn, Stanley, I
    Sigurdsson, Engilbert
    Sinnamon, Grant C. B.
    Smit, Johannes H.
    Smith, Daniel J.
    Stefansson, Hreinn
    Steinberg, Stacy
    Streit, Fabian
    Strohmaier, Jana
    Tansey, Katherine E.
    Teismann, Henning
    Teumer, Alexander
    Thompson, Wesley
    Thomson, Pippa A.
    Thorgeirsson, Thorgeir E.
    Traylor, Matthew
    Treutlein, Jens
    Trubetskoy, Vassily
    Uitterlinden, Andre G.
    Umbricht, Daniel
    Van der Auwera, Sandra
    van Hemert, Albert M.
    Viktorin, Alexander
    Visscher, Peter M.
    Wang, Yunpeng
    Webb, Bradley T.
    Weinsheimer, Shantel Marie
    Wellmann, Juergen
    Willemsen, Gonneke
    Witt, Stephanie H.
    Wu, Yang
    Xi, Hualin S.
    Yang, Jian
    Zhang, Futao
    Arolt, Volker
    Baune, Bernhard T.
    Berger, Klaus
    Boomsma, Dorret, I
    Cichon, Sven
    Dannlowski, Udo
    de Geus, E. J. C.
    DePaulo, J. Raymond
    Domenici, Enrico
    Domschke, Katharina
    Esko, Tonu
    Grabe, Hans J.
    Hamilton, Steven P.
    Hayward, Caroline
    Heath, Andrew C.
    Kendler, Kenneth S.
    Kloiber, Stefan
    Lewis, Glyn
    Li, Qingqin S.
    Lucae, Susanne
    Madden, Pamela A. F.
    Magnusson, Patrik K.
    Martin, Nicholas G.
    McIntosh, Andrew M.
    Metspalu, Andres
    Mors, Ole
    Mortensen, Preben Bo
    Mueller-Myhsok, Bertram
    Nordentoft, Merete
    Noethen, Markus M.
    O'Donovan, Michael C.
    Paciga, Sara A.
    Pedersen, Nancy L.
    Penninx, Brenda W. J. H.
    Perlis, Roy H.
    Porteous, David J.
    Potash, James B.
    Preisig, Martin
    Rietschel, Marcella
    Schaefer, Catherine
    Schulze, Thomas G.
    Smoller, Jordan W.
    Stefansson, Kari
    Tiemeier, Henning
    Uher, Rudolf
    Voelzke, Henry
    Weissman, Myrna M.
    Werge, Thomas
    Lewis, Cathryn M.
    Levinson, Douglas F.
    Borglum, Anders D.
    Sullivan, Patrick F.
    Meier, Sandra
    Strauss, John
    Xu, Wei
    Vincent, John B.
    Matthews, Keith
    Ferreira, Manuel
    O'Dushlaine, Colm
    Purcell, Shaun
    Raychaudhuri, Soumya
    Ruderfer, Douglas M.
    Sklar, Pamela
    Scott, Laura J.
    Flickinger, Matthew
    Burmeister, Margit
    Li, Jun
    Guan, Weihua
    Absher, Devin
    Thompson, Robert C.
    Meng, Fan Guo
    Schatzberg, Alan F.
    Bunney, William E.
    Barchas, Jack D.
    Watson, Stanley J.
    Myers, Richard M.
    Akil, Huda
    Boehnke, Michael
    Chambert, Kimberly
    Moran, Jennifer
    Scolnick, Edward
    Djurovic, Srdjan
    Melle, Ingrid
    Morken, Gunnar
    Corvin, Aiden
    Anjorin, Adebayo
    Kandaswamy, Radhika
    Lawrence, Jacob
    McLean, Alan W.
    Pickard, Benjamin S.
    Bergen, Sarah E.
    Nimgaonkar, Vishwajit
    Landen, Mikael
    Schalling, Martin
    Osby, Urban
    Backlund, Lena
    Frisen, Louise
    Langstrom, Niklas
    Stahl, Eli
    Dobbyn, Amanda
    Jamain, Stephane
    Etain, Bruno
    Bellivier, Frank
    Leber, Markus
    Maaser, Anna
    Fischer, Sascha B.
    Reinbold, Celine S.
    Kittel-Schneider, Sarah
    Fullerton, Janice M.
    Oruc, Lilijana
    Para, Jose G.
    Mayoral, Fermin
    Rivas, Fabio
    Czerski, Piotr M.
    Kammerer-Ciernioch, Jutta
    Vedder, Helmut
    Borrmann-Hassenbach, Margitta
    Pfennig, Andrea
    Brennan, Paul
    McKay, James D.
    Kogevinas, Manolis
    Schwarz, Markus
    Schofield, Peter R.
    Muehleisen, Thomas W.
    Schumacher, Johannes
    Bauer, Michael
    Wright, Adam
    Mitchell, Philip B.
    Hautzinger, Martin
    Kelsoe, John R.
    Greenwood, Tiffany A.
    Nievergelt, Caroline M.
    Shilling, Paul D.
    Smith, Erin N.
    Bloss, Cinnamon S.
    Edenberg, Howard J.
    Koller, Daniel L.
    Gershon, Elliot S.
    Liu, Chunyu
    Badner, Judith A.
    Scheftner, William A.
    Lawson, William B.
    Nwulia, Evaristus A.
    Hipolito, Maria
    Coryell, William
    Rice, John
    Byerley, William
    McMahon, Francis J.
    Lohoff, Falk W.
    Zandi, Peter P.
    Mahon, Pamela B.
    McInnis, Melvin G.
    Zollner, Sebastian
    Zhang, Peng
    Szelinger, Szabolcs
    St Clair, David
    Caesar, Sian
    Gordon-Smith, Katherine
    Fraser, Christine
    Green, Elaine K.
    Grozeva, Detelina
    Hamshere, Marian L.
    Kirov, George
    Nikolov, Ivan
    Collier, David A.
    Elkin, Amanda
    Williamson, Richard
    Young, Allan H.
    Ferrier, I. Nicol
    Milanova, Vihra
    Alda, Martin
    Cervantes, Pablo
    Cruceanu, Cristiana
    Rouleau, Guy A.
    Turecki, Gustavo
    Paciga, Sara
    Winslow, Ashley R.
    Grigoroiu-Serbanescu, Maria
    Ophoff, Roel
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Del-Favero, Jurgen
    Pato, Carlos
    Biernacka, Joanna M.
    Frye, Mark A.
    Morris, Derek
    Schork, Nicholas J.
    Reif, Andreas
    Lissowska, Jolanta
    Hauser, Joanna
    Szeszenia-Dabrowska, Neonila
    McGhee, Kevin
    Quinn, Emma
    Moskvina, Valentina
    Holmans, Peter A.
    Farmer, Anne
    Kennedy, James L.
    Andreassen, Ole A.
    Mattingsdal, Morten
    Bass, Nicholas J.
    Gurling, Hugh
    McQuillin, Andrew
    Breuer, Rene
    Hultman, Christina
    Lichtenstein, Paul
    Huckins, Laura M.
    Leboyer, Marion
    Lathrop, Mark
    Nurnberger, John
    Steffens, Michael
    Foroud, Tatiana M.
    Berrettini, Wade H.
    Craig, David W.
    Shi, Jianxin
    Applying polygenic risk scoring for psychiatric disorders to a large family with bipolar disorder and major depressive disorder2018In: Communications Biology, ISSN 2399-3642, Vol. 1, article id 163Article in journal (Refereed)
    Abstract [en]

    Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree (n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected individuals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.

  • 39.
    Degerman, Sofie
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Josefsson, Maria
    Umeå University, Faculty of Social Sciences, Centre for Demographic and Ageing Research (CEDAR).
    Nordin Adolfsson, Annelie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Wennstedt, Sigrid
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Landfors, Mattias
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Haider, Zahra
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Pudas, Sara
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hultdin, Magnus
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Maintained memory in aging is associated with young epigenetic age2017In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 55, p. 167-171Article in journal (Refereed)
    Abstract [en]

    Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden. A lower delta DNAm age was observed for those with maintained memory functions compared with those with average (p = 0.035) or accelerated decline (p = 0.037). Moreover, separate analyses revealed that DNAm age at follow-up, but not chronologic age, was a significant predictor of dementia (p = 0.019). Our findings suggest that young epigenetic age contributes to maintained memory in aging.

  • 40. 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, p. 11647-11656Article 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.

  • 41.
    Ekholm, Birgit
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Ekholm, Andreas
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Vares, Maria
    Osby, Urban
    Sedvall, Göran C
    Jönsson, Erik G
    Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses.2005In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 59, no 6, p. 457-464Article in journal (Refereed)
    Abstract [en]

    We aimed to estimate the value of structured interviews, medical records and Swedish register diagnoses for assessing lifetime diagnosis of patients with schizophrenia. Psychiatric records and diagnostic interviews of 143 Swedish patients diagnosed by their treating physician with schizophrenia and related disorders were scrutinized. Based on record analysis only, or a combined record and interview analysis, DSM-IV diagnoses were obtained by the OPCRIT algorithm. Independent of the OPCRIT algorithm, a standard research DSM-IV diagnosis, based on both record and interview analysis, was given by the research psychiatrist. Concordance rates for the different psychosis diagnoses were calculated. DSM-IV diagnoses based on records only, showed a good to excellent agreement with diagnoses based on records and interviews. Swedish register diagnoses displayed generally poor agreement with the research diagnoses. Nevertheless, 94% of subjects sometimes registered with a diagnosis of schizophrenic psychoses (i.e. schizophrenia, schizoaffective psychosis or schizophreniform disorder) displayed a standard research DSM-IV diagnosis of these disorders. For patients in long-term treatment for schizophrenia in Sweden, psychiatric record reviews should be optimal, cost effective and sufficient for assessment of lifetime research diagnoses of schizophrenia. For these patients a research interview adds little new information. The results further indicate that a Swedish register diagnosis of schizophrenic psychoses has a high positive predictive power to a standard research DSM-IV diagnosis of the disorders. It is concluded that for future Swedish large-scale genetic studies focusing on a broad definition of schizophrenia, it would be sufficient to rely on the Swedish register diagnoses of schizophrenic psychosis.

  • 42. Ekström, Ingrid
    et al.
    Sjölund, Sara
    Nordin, Steven
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    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.
    Nilsson, Lars-Göran
    Larsson, Maria
    Olofsson, Jonas K.
    Smell Loss Predicts Mortality Risk Regardless of Dementia Conversion2017In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 6, p. 1238-1243Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine whether dementia could explain the association between poor olfactory performance and mortality risk within a decade-long follow-up period. Design: Prospective cohort study. SettingBetula Study, Umea, Sweden. ParticipantsA population-based sample of adult participants without dementia at baseline aged 40 to 90 (N = 1,774). Measurements: Olfactory performance using the Scandinavian Odor-Identification Test (SOIT) and self-reported olfactory function; several social, cognitive, and medical risk factors at baseline; and incident dementia during the following decade. Results: Within the 10-year follow-up, 411 of 1,774 (23.2%) participants had died. In a Cox model, the association between higher SOIT score and lower mortality was significant (hazard ratio (HR) = 0.74 per point interval, 95% confidence interval (CI) = 0.71-0.77, P < .001). The effect was attenuated, but remained significant, after controlling for age, sex, education, and health-related and cognitive variables (HR = 0.92, 95% CI = 0.87-0.97, P = .001). The association between SOIT score and mortality was retained after controlling for dementia conversion before death (HR = 0.92, 95% CI = 0.87-0.97, P = .001). Similar results were obtained for self-reported olfactory dysfunction. Conclusion: Poor odor identification and poor self-reported olfactory function are associated with greater likelihood of future mortality. Dementia does not attenuate the association between olfactory loss and mortality, suggesting that olfactory loss might mark deteriorating health, irrespective of dementia.

  • 43. 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, p. 31-40Article 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.

  • 44.
    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.

  • 45.
    Eriksson Sörman, Daniel
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Aging Research Center (ARC), Karolinska Institutet, Stockholm, Sweden .
    Social relationships and risk of dementia: a population-based study2015In: International psychogeriatrics, ISSN 1041-6102, E-ISSN 1741-203X, Vol. 27, no 8, p. 1391-1399Article in journal (Refereed)
    Abstract [en]

    Background: The objective was to examine whether aspects of social relationships in old age are associated with all-cause dementia and Alzheimer's disease (AD).

    Methods: We studied 1,715 older adults (≥ 65 years) who were dementia-free at baseline over a period of up to 16 years. Data on living status, contact/visit frequency, satisfaction with contact frequency, and having/not having a close friend were analyzed using Cox proportional hazards regressions with all-cause dementia or AD as the dependent variable. To control for reverse causality and to identify potential long-term effects, we additionally performed analyses with delayed entry.

    Results: We identified 373 incident cases of dementia (207 with AD) during follow-up. The variable visiting/visits from friends was associated with reduced risk of all-cause dementia. Further, a higher value on the relationships index (sum of all variables) was associated with reduced risk of all-cause dementia and AD. However, in analyses with delayed entry, restricted to participants with a survival time of three years or more, none of the social relationship variables was associated with all-cause dementia or AD.

    Conclusions: The results indicate that certain aspects of social relationships are associated with incident dementia or AD, but also that these associations may reflect reverse causality. Future studies aimed at identifying other factors of a person's social life that may have the potential to postpone dementia should consider the effects of reverse causality.

  • 46.
    Eriksson Sörman, Daniel
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Sundström, Anna
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Social Sciences, Centre for Population Studies (CPS).
    Rönnlund, Michael
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University, Sweden .
    Leisure Activity in Old Age and Risk of Dementia: a 15-Year Prospective Study2014In: The journals of gerontology. Series B, Psychological sciences and social sciences, ISSN 1079-5014, E-ISSN 1758-5368, Vol. 69, no 4, p. 493-501Article in journal (Refereed)
    Abstract [en]

    Objectives. The aim of this study was to investigate whether leisure activity is associated with incident dementia in an older sample.

    Method. We examined a sample of 1,475 elderly (>= 65 years) who were dementia free at baseline over a follow-up period of up to 15 years. In addition to analyses involving the total time period, separate analyses of three time periods were performed, 1-5, 6-10, and 11-15 years, following baseline measurement of leisure activity.

    Results. After controlling for a variety of potential confounders, analyses of data for the total time period revealed that higher levels of "Total activity" and "Social activity," but not "Mental activity," were associated with decreased risk of dementia. However, analyses of the separate time periods showed that this association was only significant in the first time period, 1-5 years after baseline.

    Discussion. The results from this study provide little support for the hypothesis that frequent engagement in leisure activities among elderly serve to protect against dementia diseases across a longer time frame. The finding of a relationship for the first time period, 1-5 years after baseline, could indicate short-term protective effects but could also reflect reverse causality.

  • 47.
    Fernandes, Carla Patricia Duarte
    et al.
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Westlye, Lars Tjelta
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Giddaluru, Sudheer
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Christoforou, Andrea
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Kauppi, Karolina
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, Lars-Göran
    Department of Psychology, Stockholm University and Stockholm Brain Institute, Uppsala, Sweden.
    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.
    Lundervold, Astri Johansen
    Department of Biological and Medical Psychology, K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital.
    Reinvang, Ivar
    Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Steen, Vidar Martin
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Le Hellard, Stéphanie
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
    Espeseth, Thomas
    K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Department of Psychology, University of Oslo, Oslo N-0317, Norway.
    Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations2014In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 222, no 1-2, p. 60-66Article in journal (Refereed)
    Abstract [en]

    The rs1344706 single nucleotide polymorphism within intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuroimaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomical atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.

  • 48.
    Figueira, Joao
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nordin Adolfsson, Annelie
    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.
    Serum Metabolite Markers of Dementia Through Quantitative NMR Analysis: The Importance of Threonine-Linked Metabolic Pathways2019In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 69, no 3, p. 763-774Article in journal (Refereed)
    Abstract [en]

    There is a great need for diagnostic biomarkers of impending dementia. Metabolite markers in blood have been investigated in several studies, but inconclusive findings encourage further investigation, particularly in the pre-diagnostic phase. In the present study, the serum metabolomes of 110 dementia or pre-diagnostic dementia individuals and 201 healthy individuals matched for age, gender, and education were analyzed by nuclear magnetic resonance spectroscopy in combination with multivariate data analysis. 58 metabolites were quantified in each of the 311 samples. Individuals with dementia were discriminated from controls using a panel of seven metabolites, while the pre-diagnostic dementia subjects were distinguished from controls using a separate set of seven metabolites, where threonine was a common significant metabolite in both panels. Metabolite and pathway alterations specific for dementia and pre-diagnostic dementia were identified, in particular a disturbed threonine catabolism at the pre-diagnostic stage that extends to several threonine-linked pathways at the dementia stage.

  • 49.
    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, p. 2562-2571Article 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.

  • 50. 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, p. 68-74Article 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.

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