Neural correlates of executive function and working memory in the 'at risk mental state'

Background and Aims: People with ‘prodromal’ symptoms have a very high risk of developing psychosis. We used functional MRI to examine the neurocognitive basis of this vulnerability. Method: Cross-sectional comparison of subjects with an ARMS (n=17), first episode schizophreniform psychosis (n=10) and healthy volunteers (n=15). Subjects were studied using functional MRI while they performed an overt verbal fluency task, a random movement generation paradigm and an N-Back working memory task. Results: During an N-Back task the ARMS group engaged inferior frontal and posterior parietal cortex less than controls but more than the first episode group. During a motor generation task, the ARMS group showed less activation in the left inferior parietal cortex than controls, but greater activation than the first episode group. During verbal fluency using ‘Easy’ letters, the ARMS group demonstrated intermediate activation in the left inferior frontal cortex, with first episode groups showing least, and controls most, activation. When processing ‘Hard’ letters, differential activation was evident in two left inferior frontal regions. In its dorsolateral portion, the ARMS group showed less activation than controls but more than the first episode group, while in the opercular part of the left inferior frontal gyrus / anterior insula activation was greatest in the first episode group, weakest in controls and intermediate in the ARMS group. Conclusions: The ARMS is associated with abnormalities of regional brain function that are qualitatively similar to those in patients who have just developed psychosis but less severe

Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival