High brain serotonin levels in migraine between attacks:A 5-HT₄ receptor binding PET study

Migraine has been hypothesized to be a syndrome of chronic low serotonin (5-HT) levels, but investigations of brain 5-HT levels have given equivocal results. Here, we used positron emission tomography (PET) imaging of the 5-HT4 receptor as a proxy for brain 5-HT levels. Given that the 5-HT4 receptor is inversely related to brain 5-HT levels, we hypothesized that between attacks migraine patients would have higher 5-HT4 receptor binding compared to controls. Eighteen migraine patients without aura (migraine free >48 h), and 16 age- and sex-matched controls underwent PET scans after injection of [11C]SB207145, a specific 5-HT4 receptor radioligand. An investigator blinded to group calculated a neocortical mean [11C]SB207145 binding potential (BPND). Three migraine patients reported a migraine attack within 48 h after the scan and were excluded from the primary analysis. Comparing 15 migraine patients and 16 controls, we found that migraine patients have significantly lower neocortical 5-HT4 receptor binding than controls (0.60 ± 0.09 vs. 0.67 ± 0.05, p = .024), corrected for 5-HTTLPR genotype, sex and age. We found no association between 5-HT4 receptor binding and attack frequency, years with migraine or time since last migraine attack. Our finding of lower 5-HT4 receptor binding in migraine patients is suggestive of higher brain 5-HT levels. This is in contrast with the current belief that migraine is associated with low brain 5-HT levels. High brain 5-HT levels may represent a trait of the migraine brain or it could be a consequence of migraine attacks. Keywords: Headache, Pain, Neuroimaging, Brain, Serotonergic mechanism

A large population-based investigation into the genetics of susceptibility to gastrointestinal infections and the link between gastrointestinal infections and mental illness.

Gastrointestinal infections can be life threatening, but not much is known about the host's genetic contribution to susceptibility to gastrointestinal infections or the latter's association with psychiatric disorders. We utilized iPSYCH, a genotyped population-based sample of individuals born between 1981 and 2005 comprising 65,534 unrelated Danish individuals (45,889 diagnosed with mental disorders and 19,645 controls from a random population sample) in which all individuals were linked utilizing nationwide population-based registers to estimate the genetic contribution to susceptibility to gastrointestinal infections, identify genetic variants associated with gastrointestinal infections, and examine the link between gastrointestinal infections and psychiatric and neurodevelopmental disorders. The SNP heritability of susceptibility to gastrointestinal infections ranged from 3.7% to 6.4% on the liability scale. Significant correlations were found between gastrointestinal infections and the combined group of mental disorders (OR = 2.09; 95% CI: 1.82-2.4, P = 1.87 × 10-25). Correlations with autism spectrum disorder, attention deficit hyperactivity disorder, and depression were also significant. We identified a genome-wide significant locus associated with susceptibility to gastrointestinal infections (OR = 1.13; 95% CI: 1.08-1.18, P = 2.9 × 10-8), where the top SNP was an eQTL for the ABO gene. The risk allele was associated with reduced ABO expression, providing, for the first time, genetic evidence to support previous studies linking the O blood group to gastrointestinal infections. This study also highlights the importance of integrative work in genetics, psychiatry, infection, and epidemiology on the road to translational medicine

SIP Draft Specification

A Submission Information Package (SIP) is defined in the OAIS standard1 as an Information Package that is delivered by the Producer to the OAIS for use in the construction or update of one or more AIPs and/or the associated Descriptive Information. Many different SIP formats are used all over the world and unfortunately there is currently no central format for a SIP which would cover all individual national and business needs identified in the E-ARK Report on Available Best Practices. Therefore, the main objective of this report is to describe a draft SIP specification for the E-ARK project – give an overview of the structure and main metadata elements for E-ARK SIP and provide initial input for the technical implementations of E-ARK ingest tools. The target group of this work are E-ARK project partners as well as all other archival institutions and software providers creating or updating their SIP format specifications. This report provides an overview of: • The general structure for submission information packages. This report explains how the E-ARK SIP is constructed by following the common rules for all other (archival, dissemination) information packages. • The SIP METS Profile. We provide a detailed overview of metadata sections and the metadata elements in these sections. The table with all metadata elements could possibly be of interest to technical stakeholders who wish to continue with the more detailed work of the E-ARK SIP implementation later. Two examples with different kinds of content (MoReq2010, SIARD-E) following the common structure for EARK submission information package can be found in the appendixes to this report