Showing papers by "Catharina Lavebratt published in 2012"

Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset

Abstract: Even though schizophrenia has a strong hereditary component, departures from simple genetic transmission are prominent. DNA methylation has emerged as an epigenetic explanatory candidate of schizophrenia's nonmendelian characteristics. To investigate this assumption, we examined genome-wide (global) and gene-specific DNA methylation levels, which are associated with genomic stability and gene expression activity, respectively. Analyses were conducted using DNA from leukocytes of patients with schizophrenia and controls. Global methylation results revealed a highly significant hypomethylation in patients with schizophrenia (P<2.0×10−6) and linear regression among patients generated a model in which antipsychotic treatment and disease onset explained 11% of the global methylation variance (adjusted R2=0.11, ANOVA P<0.001). Specifically, haloperidol was associated with higher (“control-like”) methylation (P=0.001), and early onset (a putative marker of schizophrenia severity) was associated with lower methyl...

Antidepressant treatment is associated with epigenetic alterations in the promoter of P11 in a genetic model of depression.

Abstract: P11 (S100A10) has been associated with the pathophysiology of depression both in human and rodent models Different types of antidepressants have been shown to increase P11 levels in distinct brain regions and P11 gene therapy was recently proven effective in reversing depressive-like behaviours in mice However, the molecular mechanisms that govern P11 gene expression in response to antidepressants still remain elusive In this study we report decreased levels of P11, associated with higher DNA methylation in the promoter region, in the prefrontal cortex of the Flinders Sensitive Line (FSL) genetic rodent model of depression This hypermethylated pattern was reversed to normal, as indicated by the control line, after chronic administration of escitalopram (a selective serotonin reuptake inhibitor; SSRI) The escitalopram-induced hypomethylation was associated with both an increase in P11 gene expression and a reduction in mRNA levels of two DNA methyltransferases that have been shown to maintain DNA methylation in adult forebrain neurons (Dnmt1 and Dnmt3a) In conclusion, our data further support a role for P11 in depression-like states and suggest that this gene is controlled by epigenetic mechanisms that can be affected by antidepressant treatment

Epigenetic regulation in obesity.

Abstract: The availability to the DNA strand and the activity of the transcription machinery is crucial for the cell to use the information in the DNA. The epigenetic mechanisms DNA methylation, modification of histone tails, other chromatin-modifying processes and interference by small RNAs regulate the cell-type-specific DNA expression. Epigenetic marks can be more or less plastic perpetuating responses to various molecular signals and environmental stimuli, but in addition apparently stochastic epigenetic marks have been found. There is substantial evidence from animal and man demonstrating that both transient and more long-term epigenetic mechanisms have a role in the regulation of the molecular events governing adipogenesis and glucose homeostasis. Intrauterine exposure such as poor maternal nutrition has consistently been demonstrated to contribute to a particular epigenotype and thereby developmental metabolic priming of the exposed offspring in animal and man. Epigenetic modifications can be passed not only from one cell generation to the next, but metabolic disease-related epigenotypes have been proposed to also be transmitted germ-line. Future more comprehensive knowledge on epigenetic regulation will complement genome sequence data for the understanding of the complex etiology of obesity and related disorder.

Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA

Abstract: Background Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals.

P2RX7: Expression Responds to Sleep Deprivation and Associates with Rapid Cycling in Bipolar Disorder Type 1

Abstract: Context: Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatmentresponsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling. Objectives: To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients. Design: Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients.