Maarit A. Laaksonen

Serum vitamin D and subsequent occurrence of type 2 diabetes.

Background: Low vitamin D status has been suggested as a risk factor for type 2 diabetes. Although the epidemiologic evidence is scarce, 2 recent studies have suggested an association. The present study investigated the relation of serum vitamin D with type 2 diabetes incidence using pooled data from these 2 cohorts. Methods: Two nested case-control studies, collected by the Finnish Mobile Clinic in 1973–1980, were pooled for analysis. The study populations consisted of men and women aged 40–74 years and free of diabetes at baseline. During a follow-up period of 22 years, 412 incident type 2 diabetes cases occurred, and 986 controls were selected by individual matching. Serum vitamin D (serum 25(OH)D) was determined from frozen samples, stored at baseline. Pooled estimates of the relationship between serum vitamin D concentration and type 2 diabetes incidence were calculated. Results: Men had higher serum vitamin D concentrations than women and showed a reduced risk of type 2 diabetes in their highest vitamin D quartile. The relative odds between the highest and lowest quartiles was 0.28 (95% confidence interval = 0.10–0.81) in men and 1.14 (0.60–2.17) in women after adjustment for smoking, body mass index, physical activity, and education. Conclusions: The results support the hypothesis that high vitamin D status provides protection against type 2 diabetes. Residual confounding may contribute to this association.

Randomized trial on the effectiveness of long-and short-term psychodynamic psychotherapy and solution-focused therapy on psychiatric symptoms during a 3-year follow-up

BACKGROUND Insufficient evidence exists for a viable choice between long- and short-term psychotherapies in the treatment of psychiatric disorders. The present trial compares the effectiveness of one long-term therapy and two short-term therapies in the treatment of mood and anxiety disorders. METHOD In the Helsinki Psychotherapy Study, 326 out-patients with mood (84.7%) or anxiety disorder (43.6%) were randomly assigned to three treatment groups (long-term psychodynamic psychotherapy, short-term psychodynamic psychotherapy, and solution-focused therapy) and were followed up for 3 years from start of treatment. Primary outcome measures were depressive symptoms measured by self-report Beck Depression Inventory (BDI) and observer-rated Hamilton Depression Rating Scale (HAMD), and anxiety symptoms measured by self-report Symptom Check List Anxiety Scale (SCL-90-Anx) and observer-rated Hamilton Anxiety Rating Scale (HAMA). RESULTS A statistically significant reduction of symptoms was noted for BDI (51%), HAMD (36%), SCL-90-Anx (41%) and HAMA (38%) during the 3-year follow-up. Short-term psychodynamic psychotherapy was more effective than long-term psychodynamic psychotherapy during the first year, showing 15-27% lower scores for the four outcome measures. During the second year of follow-up no significant differences were found between the short-term and long-term therapies, and after 3 years of follow-up long-term psychodynamic psychotherapy was more effective with 14-37% lower scores for the outcome variables. No statistically significant differences were found in the effectiveness of the short-term therapies. CONCLUSIONS Short-term therapies produce benefits more quickly than long-term psychodynamic psychotherapy but in the long run long-term psychodynamic psychotherapy is superior to short-term therapies. However, more research is needed to determine which patients should be given long-term psychotherapy for the treatment of mood or anxiety disorders.

Prospective study of coffee consumption and risk of Parkinson's disease

Objective:To examine the prediction of coffee consumption on the incidence of Parkinsons disease.Subjects and methods:The study population comprised 6710 men and women, aged 50–79 years and free from Parkinsons disease at the baseline. At baseline, enquiries were made about coffee consumption in a self-administered questionnaire as the average number of cups per day. During a 22-year follow-up, 101 incident cases of Parkinsons disease occurred. Parkinsons disease cases were identified through a nationwide registry of patients receiving medication reimbursement, which is based on certificates from neurologist.Results:After adjustments for age, sex, marital status, education, community density, alcohol consumption, leisure-time physical activity, smoking, body mass index, hypertension and serum cholesterol, the relative risk for subjects drinking 10 or more cups of coffee per day compared with non-drinkers was 0.26 (95% confidence interval 0.07–0.99, P-value for trend=0.18). The association was stronger among overweight persons and among persons with lower serum cholesterol level (P-value for interaction=0.04 and 0.03, respectively).Conclusions:The results support the hypothesis that coffee consumption reduces the risk of Parkinsons disease, but protective effect of coffee may vary by exposure to other factors.

Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption

Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968-72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases.

Quasi-experimental study on the effectiveness of psychoanalysis, long-term and short-term psychotherapy on psychiatric symptoms, work ability and functional capacity during a 5-year follow-up

BACKGROUND Psychotherapy is apparently an insufficient treatment for some patients with mood or anxiety disorder. In this study the effectiveness of short-term and long-term psychotherapies was compared with that of psychoanalysis. METHODS A total of 326 psychiatric outpatients with mood or anxiety disorder were randomly assigned to solution-focused therapy, short-term psychodynamic and long-term psychodynamic psychotherapies. Additionally, 41 patients suitable for psychoanalysis were included in the study. The patients were followed from the start of the treatment and assessed 9 times during a 5-year follow-up. The primary outcome measures on symptoms were the Beck Depression Inventory, the Hamilton Depression and Anxiety Rating Scales, and the Symptom Check List, anxiety scale. Primary work ability and functional capacity measures were the Work Ability Index, the Work-subscale of the Social Adjustment Scale, and the Perceived Psychological Functioning Scale. RESULTS A reduction in psychiatric symptoms and improvement in work ability and functional capacity was noted in all treatment groups during the 5-year follow-up. The short-term therapies were more effective than psychoanalysis during the first year, whereas the long-term therapy was more effective after 3years of follow-up. Psychoanalysis was most effective at the 5-year follow-up, which also marked the end of the psychoanalysis. CONCLUSIONS Psychotherapy gives faster benefits than psychoanalysis, but in the long run psychoanalysis seems to be more effective. Results from trials, among patients suitable for psychoanalysis and with longer follow-up, are needed before firm conclusions about the relative effectiveness of psychoanalysis and psychotherapy in the treatment of mood and anxiety disorders can be drawn.

A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern

BACKGROUND The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases. OBJECTIVE To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP. METHODS We ascertained ERP on the basis of electrocardiograms in 3 large community-based cohorts from Europe and the United States: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed genome-wide association studies in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached P ≤ 1 × 10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages. RESULTS Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9 ± 8.9 years, 30.3% women; ERP negative: 47.5 ± 9.4 years, 54.2% women). After meta-analysis, 8 single nucleotide polymorphisms reached P ≤ 1 × 10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95% confidence interval 0.36-0.61; P = 6.9 × 10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95% confidence interval 1.25-1.69; P = 8.5 × 10(-7)). In the replication step (7151 individuals), none of the 8 variants replicated, and combined meta-analysis results failed to reach genome-wide significance. CONCLUSIONS In a genome-wide association study, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations.

A Metabolic Shift Favoring Sphingosine 1-Phosphate at the Expense of Ceramide Controls Glioblastoma Angiogenesis

Background: The sphingolipid metabolite sphingosine 1-phosphate (S1P) is a potent angiogenic factor. Results: S1P content is 9-fold higher in glioblastomas compared with normal brain, and S1P production is necessary for glioblastoma cells to trigger endothelial cell angiogenesis. Conclusion: Excessive S1P synthesis is a major contributor to glioblastoma angiogenesis. Significance: Inhibiting S1P synthesis may be a valuable antiangiogenic approach in glioblastoma. Studies in cell culture and mouse models of cancer have indicated that the soluble sphingolipid metabolite sphingosine 1-phosphate (S1P) promotes cancer cell proliferation, survival, invasiveness, and tumor angiogenesis. In contrast, its metabolic precursor ceramide is prodifferentiative and proapoptotic. To determine whether sphingolipid balance plays a significant role in glioma malignancy, we undertook a comprehensive analysis of sphingolipid metabolites in human glioma and normal gray matter tissue specimens. We demonstrate, for the first time, a systematic shift in sphingolipid metabolism favoring S1P over ceramide, which increases with increasing cancer grade. S1P content was, on average, 9-fold higher in glioblastoma tissues compared with normal gray matter, whereas the most abundant form of ceramide in the brain, C18 ceramide, was on average 5-fold lower. Increased S1P content in the tumors was significantly correlated with increased sphingosine kinase 1 (SPHK1) and decreased sphingosine phosphate phosphatase 2 (SGPP2) expression. Inhibition of S1P production by cultured glioblastoma cells, using a highly potent and selective SPHK1 inhibitor, blocked angiogenesis in cocultured endothelial cells without affecting VEGF secretion. Our findings validate the hypothesis that an altered ceramide/S1P balance is an important feature of human cancers and support the development of SPHK1 inhibitors as antiangiogenic agents for cancer therapy.

Sagittal Abdominal Diameter as a New Predictor for Incident Diabetes

OBJECTIVE Obesity, particularly visceral adiposity, is a major risk factor for type 2 diabetes. The commonly used obesity indicators, BMI, waist girth, and waist-to-hip ratio (WHR), have limited ability to measure the visceral adipose tissue. Sagittal abdominal diameter (SAD) has been shown to predict the amount of visceral fat. So far no study has been published on its ability to predict diabetes occurrence. RESEARCH DESIGN AND METHODS We assessed and compared the prediction of the four obesity indicators for diabetes incidence in a prospective study based on 5,168 participants from the nationally representative Health 2000 study. RESULTS During a mean follow-up lasting 8.1 years, 222 incident diabetes cases occurred. In multivariate models adjusted for lifestyle factors, BMI, waist girth, WHR, and SAD were significant predictors of diabetes incidence. The relative risks (95% CI) between high and low levels were 15.0 (6.94–32.6), 11.4 (5.39–23.8), 12.5 (6.47–24.2), and 14.7 (6.89–31.2), respectively. Pairwise interaction analysis showed that the co-occurrence of high BMI and high SAD was associated with the highest diabetes incidence, with a relative risk of 37.0 (11.2–122). After adjustment for waist girth and the components of the metabolic syndrome, the relative risk was 9.88 (2.81–34.7). The corresponding population-attributable fraction estimate was 84% (49–95). CONCLUSIONS The combination of SAD and BMI measurements yields a new predictor of diabetes incidence.

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg 2/σP 2 = 25%, h 2 = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10−5 were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases.

Use of auxiliary psychiatric treatment during a 5-year follow-up among patients receiving short- or long-term psychotherapy

BACKGROUND The need for treatment is, despite of its obvious usefulness, a scarcely used measure of effectiveness in psychotherapy trials. This study considers changes in the need for auxiliary psychiatric treatment after starting short- and long-term psychotherapy and psychoanalysis. METHODS Altogether 326 psychiatric outpatients with mood or anxiety disorder were randomly assigned to solution-focused therapy (SFT), short-term psychodynamic psychotherapy (SPP), or long-term psychodynamic psychotherapy (LPP) while 41 self-selected patients were allocated to psychoanalysis (PA). The patients were followed for 5 years from start of treatment. Outcome measures were use of auxiliary psychotherapy, psychotropic medication, and hospitalization for mental reasons. RESULTS About 60% of the patients used auxiliary treatment during the follow-up. It was most common in the short-term therapy groups and its incidence was highest during the first year after the start of therapy. The average numbers of all therapy sessions among patients starting the therapy were 60, 70, 240, and 670 in SFT, SPP, LPP, and PA, respectively, whereas the corresponding average numbers of study therapy sessions alone were 10, 19, 232, and 646. Over 50% of the patients receiving short-term therapy received on average 4-6 times more therapy sessions than initially assigned. LIMITATIONS Post-randomization withdrawal was uneven. CONCLUSIONS Auxiliary treatment is usual among patients receiving short- and long-term therapies, and apparently becomes common shortly after the start of treatment. Auxiliary treatment can be used as an outcome measure indicating the need for treatment, should be monitored clinically and considered when interpreting the results of effectiveness studies.