Karolinska Institutet

About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Poison control. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.

Evidence for the existence of monoamine neurons in the central nervous system. 3. the monoamine nerve terminal.

Abstract: With the help of the highly specific and sensitive fluorescence method of Falck and Hillarp together with the histochemical and pharmacological criteria for the specificity of the fluorescence reaction convincing evidence has been obtained that the fine, varicose nerve fibres observed in a vast number of regions in the mammalian central nervous system (mouse, hamster, rat, guineapig, rabbit, cat), which exhibit a green or yellow fluorescence, contain primary catecholamines and 5-HT respectively. Strong support has been given for the view that CA fibres showing a rapid recovery after administration of α-MMT contain DA, while those showing a slow recovery contain NA. There is little doubt that the monoamine-containing fibres in the brain represent the terminal ramifications of axons belonging to specific monoamine neurons and that they are true synaptic terminals. They seem to make their contacts via the varicosities which have extremely high concentrations of amines and in all probability represent the presynaptic structures, specialized for synthesis, storage and release of the amines. The central monoamine terminals thus have the same characteristic appearance as the adrenergic synaptic terminals in the peripheral nervous system. All the data strongly support the view that the specific central neurons giving rise to the terminals are monoaminergic, i.e. function by releasing their amines from the synaptic terminals. Consequently, DA, NA and 5-HT seem to be central neurotransmitters. Not only the median eminence but also the nuc. caudatus putamen, tuberculum olfactorium, nuc. accumbens and the small circumscribed areas medial to nuc. accumbens contain very fine (partly sublightmicroscopical) CA terminals. These areas react to treatment with reserpine, nialamide-dopa and α-MMT in the same way and since the nuc. caudatus putamen and tuberculum olfactorium are known to have a high DA content it seems likely that abundant DA terminals are accumulated in these special areas.

Integrative approaches for large-scale transcriptome-wide association studies.

Abstract: Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ∼ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.

Rare chromosomal deletions and duplications increase risk of schizophrenia

Abstract: Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73 - 90% ( ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants ( CNVs) have been identified in individual patients with schizophrenia(2-7) and also in neurodevelopmental disorders(8-11), but large- scale genome- wide surveys have not been performed. Here we report a genome- wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high- density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15- fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single- occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo- cardio- facial syndrome, which includes psychotic symptoms in 30% of patients(12). Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome- wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome- wide and at specific loci.

The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity.

Abstract: IntroductionThe International Physical Activity Questionnaire (IPAQ) was developed to measure health-related physical activity (PA) in populations. The short version of the IPAQ has been tested extensively and is now used in many international studies. The present study aimed to explore the validity characteristics of the long-version IPAQ.Subjects and methodsForty-six voluntary healthy male and female subjects (age, mean±standard deviation: 40.7±10.3 years) participated in the study. PA indicators derived from the long, self-administered IPAQ were compared with data from an activity monitor and a PA log book for concurrent validity, and with aerobic fitness, body mass index (BMI) and percentage body fat for construct validity.ResultsStrong positive relationships were observed between the activity monitor data and the IPAQ data for total PA (ρ = 0.55, P < 0.001) and vigorous PA (ρ = 0.71, P < 0.001), but a weaker relationship for moderate PA (ρ = 0.21, P = 0.051). Calculated MET-h day−1 from the PA log book was significantly correlated with MET-h day−1 from the IPAQ (ρ = 0.67, P < 0.001). A weak correlation was observed between IPAQ data for total PA and both aerobic fitness (ρ = 0.21, P = 0.051) and BMI (ρ = 0.25, P = 0.009). No significant correlation was observed between percentage body fat and IPAQ variables. Bland–Altman analysis suggested that the inability of activity monitors to detect certain types of activities might introduce a source of error in criterion validation studies.ConclusionsThe long, self-administered IPAQ questionnaire has acceptable validity when assessing levels and patterns of PA in healthy adults.