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R Adolfsson

Publications and source records attributed to R Adolfsson.

At least 19 recordsLinked to original sources
PubMed2006

Increased risk of dementia following mild head injury for carriers but not for non-carriers of the APOE epsilon4 allele.

BACKGROUND: The epsilon4 allele of apolipoprotein E (APOE) and head injury are risk factors for dementia diseases, and may act synergistically to further increase the risk. The aim of this study was to examine the association between mild head injury, APOE and dementia. METHODS: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40-85 years, free of dementia at baseline, who were followed up within a 5-year interval. Dementia was classified using DSM-IV criteria. Information on previous head injury was obtained through screening of the participants' answers to health questionnaires at baseline and at follow-up. RESULTS: Subjects with head injury but without APOE epsilon4 had no increased risk of dementia. Subjects with APOE epsilon4 had an increased risk and those with both APOE epsilon4 and head injury had the highest risk of dementia (odds ratio = 5.2). CONCLUSIONS: APOE epsilon4 constitutes a risk factor for dementia, mild injury in isolation does not increase the risk, but head injury in combination with the APOE epsilon4 leads to increased risk of dementia.

Adult↗
PubMed2006

Altered brain white matter integrity in healthy carriers of the APOE epsilon4 allele: a risk for AD?

BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. METHODS: The authors used diffusion tensor imaging to investigate ultrastructural properties in brain white matter to detect pathologic processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4 allele, and 20 had the APOE epsilon34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance. RESULTS: The results showed a decline in fractional anisotropy, a marker for white matter integrity, in the posterior corpus callosum of epsilon4 carriers compared to non-carriers. Additional sites of altered white matter integrity included the medial temporal lobe. CONCLUSIONS: Although the mechanism underlying vulnerability of white matter tracts in APOE epsilon4 carriers is still unknown, these findings suggest that increased genetic risk for developing Alzheimer disease is associated with changes in microscopic white matter integrity well before the onset of dementia.

Aged↗
PubMed2004

Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease.

Malfunctioning of cyclin-dependent kinase 5 (CDK5) through aberrant proteolytic cleavage of its neuronal activators p35 and p39 is involved in neurodegeneration in Alzheimer's disease (AD) and other neurodegenerative brain diseases. By extensive genetic analysis of the genes encoding CDK5 (CDK5), p35 (CDK5R1) and p39 (CDK5R2), we excluded causal mutations in 70 familial early-onset AD patients. We performed an association study with five informative SNPs in CDK5 in two independent samples of early-onset AD patients and matched control individuals from The Netherlands and northern Sweden. Association was observed with g.149800G>C in intron 5 of CDK5, and a two times increased risk was observed in both patient samples for carriers of the C-allele. Our data are indicative for a role of the CDK5 molecular complex in the genetic etiology of early-onset AD, and suggest that a yet unknown functional variant in CDK5 or in a nearby gene might lead to increased susceptibility for early-onset AD.

Aged↗
PubMed2004

APOE influences on neuropsychological function after mild head injury: within-person comparisons.

OBJECTIVE: To examine the relationship between neuropsychological outcome following mild head injury (MHI) and APOE genotype. METHODS: Data from a population-based longitudinal study (n = 3,500) were used to identify 34 adults who experienced MHI during the course of the study. Their pre- and postinjury performances on a battery of nine neuropsychological tests were compared within person, and the postinjury performance was compared with that of age- and gender-matched control subjects. RESULTS: The within-person comparisons showed that participants with at least one APOE epsilon4 allele (n = 11) had a significantly decreased postinjury performance on three of the tests, whereas the postinjury performance for APOE epsilon4-negative participants (n = 23) was unchanged. There was no significant difference in postinjury performance between participants with/without the epsilon4 allele, and neither group was impaired relative to controls. CONCLUSIONS: APOE genotype may influence the outcome following an MHI. Pre/postinjury within-person comparisons seem more sensitive than control group comparisons for detecting injury-related effects.

Adult↗
PubMed2004

A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression.

Increasing amounts of data suggest that affective disorders might be related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the stress-response systems. Arginine vasopressin (AVP) influences several symptoms, relevant to affective disorders, notable memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). Five SNPs were identified in AVPR1b and genotyped in two well-diagnosed samples of patients with recurrent major depression and matched controls. In the Swedish sample, we observed significant allele (P=0.02) and genotype (P=0.01) association with SNP AVPR1b-s3, and in the Belgian sample, a borderline significant association with SNP AVPR1b-s5 (P=0.04). In both patient-control samples, the haplotype defined by alleles A-T-C-A-G for the AVPR1b-s SNPs s1-s2-s3-s4-s5 was significantly over-represented in controls compared to patients. Our data support a protective effect of this major haplotype for recurrent major depression.

Aged↗
PubMed2003

The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality.

BACKGROUND: Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case-control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD. METHOD: One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets. RESULTS: No association between 5-HTTLPR and SAD was found in the new case-control material, in the combined analysis of all samples, or when only including 316 patients with controls (N = 298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2.24 (1.03-4.91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set. CONCLUSIONS: These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

Adult↗
PubMed2001

A schizophrenia-susceptibility locus at 6q25, in one of the world's largest reported pedigrees.

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

Adult↗
PubMed2001

Tryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study.

BACKGROUND: Being the rate-limiting enzyme in the biosynthesis of serotonin, the tryptophan hydroxylase gene (TPH) has been considered a possible candidate gene in bipolar and unipolar affective disorders (BPAD and UPAD). Several studies have investigated the possible role of TPH polymorphisms in affective disorders and suicidal behavior. METHODS: The TPH A218C polymorphism has been investigated in 927 patients (527 BPAD and 400 UPAD) and their matched healthy control subjects collected within the European Collaborative Project on Affective Disorders. RESULTS: No difference of genotype distribution or allele distribution was found in BPAD or UPAD. No statistically significant difference was observed for allele frequency and genotypes counts. In a genotype per genotype analysis in UPAD patients with a personal history of suicide attempt, the frequency of the C-C genotype (homozygosity for the short allele) was lower in UPAD patients (24%) than in control subjects (43%) (chi(2) = 4.67, p =.03). There was no difference in allele or genotype frequency between patients presenting violent suicidal behavior (n = 48) and their matched control subjects. CONCLUSIONS: We failed to detect an association between the A218C polymorphism of the TPH gene and BPAD and UPAD in a large European sample. Homozygosity for the short allele is significantly less frequent in a subgroup of UPAD patients with a history of suicide attempt than in control subjects.

Alleles↗
PubMed2001

Seasonal affective disorder and serotonin-related polymorphisms.

Disturbances in central serotonergic systems have been hypothesized to be involved in seasonal affective disorder (SAD). Association between SAD and the shorter allele of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR) has been reported in an American sample. We have genotyped 82 SAD patients and 82 healthy controls from Sweden, Finland, and Germany for this and five other polymorphisms in the genes coding for serotonin receptors 5-HT2A and 5-HT2C, tryptophan hydroxylase and white. No associations with SAD or seasonality (seasonal variations in mood and behavior) were detected. Although minor effects cannot be excluded, our results suggest that these polymorphisms do not play a major role in the pathogenesis of SAD in the northern European population.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2001

Lack of association between GABRA3 and unipolar affective disorder: a multicentre study.

Available data on gamma amino butyric acid (GABA) support the hypothesis that a dysfunction in the brain GABAergic system activity contributes to vulnerability to affective disorders (AD), including bipolar disorder (BPAD) and unipolar disorder (UPAD). The localization of the alpha3 subunit GABA receptor (GABRA3) gene in Xq28, a region of interest for BPAD suggests that GABRA3 may be a relevant candidate gene. In the present study, we tested the genetic contribution of the GABRA3 dinucleotide polymorphism in a European multicentre UPAD case-control sample [UPAD (n = 106), controls (n = 212)]. Our negative results suggest that GABRA3 does not confer susceptibility nor is it in linkage disequilibrium with another close gene involved in the genetic aetiology of UPAD.

Adult↗
PubMed2001

Variability of 5-HT2C receptor cys23ser polymorphism among European populations and vulnerability to affective disorder.

Substantial evidence supports a role for dysfunction of brain serotonergic (5-HT) systems in the pathogenesis of major affective disorder, both unipolar (recurrent major depression) and bipolar.(1) Modification of serotonergic neurotransmission is pivotally implicated in the mechanism of action of antidepressant drugs(2) and also in the action of mood stabilizing agents, particularly lithium carbonate.(3) Accordingly, genes that code for the multiple subtypes of serotonin receptors that have been cloned and are expressed in brain,(4) are strong candidates for a role in the genetic etiology of affective illness. We examined a structural variant of the serotonin 2C (5-HT2C) receptor gene (HTR2C) that gives rise to a cysteine to serine substitution in the N terminal extracellular domain of the receptor protein (cys23ser),(5) in 513 patients with recurrent major depression (MDD-R), 649 patients with bipolar (BP) affective disorder and 901 normal controls. The subjects were drawn from nine European countries participating in the European Collaborative Project on Affective Disorders. There was significant variation in the frequency of the HT2CR ser23 allele among the 10 population groups included in the sample (from 24.6% in Greek control subjects to 9.2% in Scots, chi(2) = 20.9, df 9, P = 0.01). Logistic regression analysis demonstrated that over and above this inter-population variability, there was a significant excess of HT2CR ser23 allele carriers in patients compared to normal controls that was demonstrable for both the MDD (chi(2) = 7.34, df 1, P = 0.006) and BP (chi(2) = 5.45, df 1, P = 0.02) patients. These findings support a possible role for genetically based structural variation in 5-HT2C receptors in the pathogenesis of major affective disorder.

Amino Acid Substitution↗
PubMed2001

Season of birth variations in the temperament and character inventory of personality in a general population.

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.

Adult↗
PubMed2000

Long repeat tracts at SCA8 in major psychosis.

Expansion at a recently identified unstable trinucleotide repeat on chromosome 13q21 has been reported as the molecular cause for spinocerebellar ataxia type 8 (SCA8). The trinucleotide repeat, which consists of a [CTA]n repeat and adjacent [CTG]n repeat, was reported to have a pathogenic range of 107-127 CTG repeats (or 110-130 combined CTA and CTG repeats) in a large ataxia kindred. This repeat region was also cloned by our group from a bipolar affective disorder (BPAD) patient, who has approximately 600 combined repeats, and large alleles (>100 repeats) were reported to be present in 0.7% of controls and 1.5% of major psychosis patients (n = 710 and n = 1,120, respectively). We have followed up these findings by screening three new samples of BPAD and schizophrenia (SCZ) patients and controls, including 272 individuals from 14 BPAD families from Sweden, 130 individuals from 32 SCZ and BPAD families/trios from the Azores Islands, and 206 SCZ individuals from the United Kingdom and Ireland, and 219 matched controls. We found large repeat alleles above the SCA8 pathogenic range in individuals from 3 of 32 Azorean pedigrees and in 1 of 206 SCZ individuals from the United Kingdom, and repeat alleles within the SCA8 pathogenic range in 1 of 14 Swedish families. Although the rarity of major psychosis patients carrying the SCA8 expansion mutation would require a much larger sample size to reach statistical significance, these results support the previously reported observation of increased occurrence of large repeats at SCA8 in major psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:873-876, 2000.

Alleles↗
PubMed2000

Power of selective genotyping in genetic association analyses of quantitative traits.

A power calculation is described in which the power of selective genotyping in genetic association studies of quantitative traits is evaluated. The method of selective genotyping implies the selection of the extremely high and low scoring individuals from the continuous distribution of a quantitative trait. The selected individuals are genotyped and association is tested. In the power calculation the following parameters are varied: total sample size of the phenotyped group (1000, 1500, 2000); selection of extremely high and low scoring individuals (2.5%, 5%, 10%); allele frequency of the risk increasing allele (0.10 to 0.90); mode of inheritance and proportion of variance explained by the quantitative trait locus (QTL) (omega 2 = 0.01, 0.05, 0.10). We conclude that the method of selective genotyping is a powerful method to detect association for a quantitative trait.

Chromosome Mapping↗
PubMed1999

Tyrosine hydroxylase polymorphism and phenotypic heterogeneity in bipolar affective disorder: a multicenter association study.

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, is considered a candidate gene in bipolar affective disorder (BPAD) and has been the subject of numerous linkage and association studies. Taken together, most results do not support a major gene effect for the TH gene in BPAD. Genetic and phenotypic heterogeneity may partially explain the difficulty of confirming the exact role of this gene using both association and linkage methods. Four hundred one BPAD patients and 401 unrelated matched controls were recruited within a European collaborative project (BIOMED1 project in the area of brain research, European Community grant number CT 92-1217, project leader: J. Mendlewicz) involving 14 centers for a case-control association study with a tetranucleotide polymorphism in the TH gene. Patients and controls were carefully matched for geographical origin. Phenotypic heterogeneity was considered and subgroup analyses were performed with relevant variables: age at onset, family history, and diagnostic stability. No association was observed in the total sample or for subgroups according to age at onset (n = 172), family history alone (n = 159), or high degree of diagnostic stability and a positive family history (n = 131). The results of this association study do not confirm the possible implication of TH polymorphism in the susceptibility to BPAD.

Adult↗
PubMed1999

Linkage analysis of a large Swedish kindred provides further support for a susceptibility locus for schizophrenia on chromosome 6p23.

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

Alleles↗
PubMed1999

Platelet [3H]paroxetine and [3H]lysergic acid diethylamide binding in seasonal affective disorder and the effect of bright light therapy.

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

Adult↗