Association of CHRM2 with IQ: Converging Evidence for a Gene Influencing Intelligence

The cholinergic neurotransmitter system is thought to be involved in many aspects of memory, attention, and higher cognition. In the Collaborative Study on the Genetics of Alcoholism (COGA) sample, we have previously reported linkage and association to the cholinergic muscarinic 2 receptor gene (CHRM2) on chromosome 7 with evoked EEG oscillations (Jones et al. 2004), providing evidence that this gene may be involved in human brain dynamics and cognition. In addition, a small number of genetic markers were genotyped in CHRM2 in the Minnesota Twin and Family Study (Comings et al. 2003) and a Dutch family study (Gosso et al. 2006, in press) and both research groups found evidence that this gene may be involved in intelligence. In the COGA sample, we have extensively genotyped SNPs within and flanking the CHRM2 gene. We find evidence of association with multiple SNPs across CHRM2 and Performance IQ, as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R). These results remain significant after taking into account alcohol dependence and depression diagnoses in the sample. Edited by Danielle Posthuma Henri Begleiter—Deceased     

Alterations in presenilin 1 processing by amyloid-β peptide in the rat retina

Accumulating evidence indicates that mutations in the presenilin 1 (PS1) gene are responsible for most cases of familial Alzheimer’s disease (AD). Although its biological functions are not yet fully understood, it appears that PS1 plays a role in the processing and trafficking of the amyloid precursor protein (APP). However, little is known about factors that are involved in regulating the metabolism of PS1 especially in relation to AD pathology. In this study, we have examined the effect of optic nerve crush, intravitreal injection of the inflammatory agent lipopolysaccharide (LPS) or injection of amyloid β_1-42 (Aβ_1-42) on the expression and processing of PS1 in the rat retina. We found that 48 h after injection of Aβ_1-42 there was a dramatic alteration in the banding pattern of PS1 on Western blots, as indicated by marked changes in the levels of expression of some of its C- and N-terminal fragments in retinal homogenates. These results suggest an Aβ_1-42-induced potentiation of a non-specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model.     

Long‐term impacts of early‐life exposure to malaria: Evidence from Taiwan's Eradication Campaign in the 1950s

This paper utilizes the eradication campaign in Taiwan in the 1950s to estimate the long‐term impacts of early‐life (in utero and postnatal) exposure to malaria. Matching adults in the 1992–2012 Taiwan Social Change Survey to the malaria intensity in their individual place and year of birth, difference‐in‐difference estimation shows strong evidence that the eradication increased men's own educational attainment as well as their family income in adulthood. We also use the 1980 census data to show there was a sharp education increase after the eradication. Furthermore, the eradication increased the educational attainment of married men's spouses. Finally, quantile regressions show that the effect concentrated on the lower percentile of the income distribution. Overall, our results suggest negative effects of early‐life exposure to malaria.     

The effects of parenteral nutrition on food intake and gastric motility

Frequently, patients receiving parenteral nutrition (PN) report hunger during the parenteral infusion, yet experience early satiety once PN is tapered off. Post-PN satiety can interfere with the ability to consume enough nutrients to maintain body weight and nutritional status. Factors such as caloric quantity of infusate, gastric motility changes, and disease pathology have been related to appetite changes. To investigate the effects of PN on food intake and gastric motility without the complicated interactions associated with disease pathology, four normal, healthy rhesus monkeys (Macaca mulatta) were studied. The monkeys were administered PN in amounts ranging from 25% to 100% of their normal daily caloric intake. Food and water were continuously available. PN consistently suppressed voluntary food intake in direct relationship to the amount of nutrient infused. The frequency of large-amplitude hunger-type gastric contractions decreased from control conditions. Upon cessation of PN, appetite remained suppressed for one to two weeks, indicating a self-limiting physiological basis to post-PN satiety. Thus, reduced appetite following PN termination might occur in the clinical setting and the patients' feelings of satiety may not be completely attributed to lack of cooperation or disease pathology.     

A dual‐tracer study of extrastriatal 6‐[18F]fluoro‐m‐tyrosine and 6‐[18F]‐fluoro‐l‐dopa Uptake in Parkinson's disease

6‐[¹⁸F]‐Fluoro‐l ‐dopa (FDOPA) has been widely used as a biomarker for catecholamine synthesis, storage, and metabolism—its intense uptake in the striatum, and fainter uptake in other brain regions, is correlated with the symptoms and pathophysiology of Parkinson's disease (PD). 6‐[¹⁸F]fluoro‐m‐tyrosine (FMT), which also targets l ‐amino acid decarboxylase, has potential advantages over FDOPA as a radiotracer because it does not form catechol‐O‐methyltransferase (COMT) metabolites. The purpose of the present study was to compare the regional distribution of these radiotracers in the brains of PD patients. Fifteen Parkinson's patients were studied with FMT and FDOPA positron emission tomography (PET) as well as high‐resolution structural magnetic resonance imaging (MRI). MRI's were automatically parcellated into neuroanatomical regions of interest (ROIs) in Freesurfer ( http://surfer.nmr.mgh.harvard.edu ); region‐specific uptake rate constants (K_occ) were generated from coregistered PET using a Patlak graphical approach. The essential findings were as follows: (1) regional K_occ were highly correlated between the radiotracers and in agreement with a previous FDOPA studies that used different ROI selection techniques; (2) FMT K_occ were higher in extrastriatal regions of relatively large uptake such as amygdala, pallidum, brainstem, hippocampus, entorhinal cortex, and thalamus, whereas cortical K_occ were similar between radiotracers; (3) while subcortical uptake of both radiotracers was related to disease duration and severity, cortical uptake was not. These results suggest that FMT may have advantages for examining pathologic changes within allocortical loop structures, which may contribute to cognitive and emotional symptoms of PD. Synapse 68:325–331, 2014 . © 2014 Wiley Periodicals, Inc.