The effect of 5-HTTLPR and a serotonergic multi-marker score on amygdala,prefrontal and anterior cingulate cortex reactivity and habituation in a large,healthy fMRI cohort

Major depressive disorder (MDD) is characterized by low mood for at least two weeks. Impaired emotion regulation has been suggested to be the consequence of dysfunctional serotonergic regulation of limbic and prefrontal regions, especially the amygdala, the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The impact of genetic variation on brain function can be investigated with intermediate phenotypes. A suggested intermediate phenotype of MDD is emotion recognition: The 5-HTTLPR polymorphism of SLC6A4 as well as other serotonergic genes have been associated with amygdala and prefrontal function during emotion recognition. Previously, it has been suggested that habituation is a more reliable index of emotion recognition than functional activation. We examined the relationship of genes involved in serotonergic signaling with amygdala as well as prefrontal functional activation and habituation during an emotion recognition task in 171 healthy subjects. While effects of 5-HTTLPR and of a serotonergic multi-marker score (5-HTTLPR, TPH1(rs1800532), TPH2(rs4570625), HTR1A(rs6295) and HTR2A(rs6311)) on amygdala activation did not withstand correction for multiple regions of interest, we observed a strong correlation of the multi-marker score and habituation in the amygdala, DLPFC, and ACC. We replicated a well-studied intermediate phenotype for association with 5-HTTLPR and provided additional evidence for polygenic involvement. Furthermore, we showed that task habituation may be influenced by genetic variation in serotonergic signaling, particularly by a serotonergic multi-marker score. We provided preliminary evidence that PFC activation is an important intermediate phenotype of MDD. Future studies are needed to corroborate the results in larger samples.     

Role of conditioned taste aversion in the development of activity anorexia

Activity anorexia (AA) occurs when rats are restricted to one meal period (60-90 min) each day and have unlimited access to a running wheel the rest of the time. This AA procedure also contains the conditions necessary for conditioned taste aversion (CTA). The food eaten during the meal period is the conditioned stimulus paired with the unconditioned stimulus produced by wheel running. Thus, CTA to food may account in part for the decreased eating in AA. To test this possibility, male rats were subjected to the AA procedure. They had daily 90-min exposures to their familiar chow and spent the rest of the day in running wheels (experimental condition) or home cages (control condition). A second, concurrent experiment had the same procedure except that novel, rather than familiar, food was used. In both experiments, AA occurred; the rats allowed to wheel run ate less than those in the control condition. Several days after AA training, a two-food preference test assessed whether CTA occurred. Wheel running induced CTA when food was novel but not when it was familiar. Since AA is typically studied with procedures using familiar food, the present findings indicate that CTA plays little or no role in AA.     

Exemptions to school immunization requirements: the role of school-level requirements, policies, and procedures

OBJECTIVES: Our goal was to determine whether school-level variability in implementation of immunization requirements is associated with the likelihood of a child having received an exemption to school immunization requirements. METHODS: We surveyed 1000 school immunization personnel in Colorado, Massachusetts, Missouri, and Washington. We explored associations between school implementation of immunization requirements and the likelihood of a child having an exemption using logistic regression models. RESULTS: School policies associated with an increased likelihood of children having exemptions included lack of provision of written instructions for completing the school immunization requirement before enrollment, administrative procedures making it easier to claim an exemption, and granting of philosophical exemptions. In the 2 states we surveyed where philosophical exemptions are not authorized (Massachusetts and Missouri), 17.0% and 18.1% of schools reported permitting philosophical exemptions. CONCLUSIONS: Inconsistencies in the interpretation and implementation of school immunization laws contribute to variability in rates of exemptions. School policies should be reviewed to ensure consistency with the intent of state laws.     

The hedonic effects of amphetamine and pentobarbital in goldfish

Goldfish were confined in a distinctive chamber while drugged with amphetamine in Experiment A or pentobarbital in Experiment P. During a later test, the goldfish in Experiment A showed a preference for the chamber associated with amphetamine, whereas those in Experiment P showed an aversion to the chamber associated with pentobarbital. Thus, amphetamine produced a rewarding effect while pentobarbital was aversive. The mechanism of pentobarbital's aversive effect is unknown. However, there is convincing evidence that amphetamine produces a rewarding effect in rats, monkeys and humans by increasing the synaptic concentration of dopamine in the central reward system. Since the goldfish brain has cells containing dopamine, the same mechanism is likely to be responsible for amphetamine's rewarding effect in goldfish. This similarity suggests that the central reward systems of such diverse species as goldfish, rats, monkeys, and humans have a common evolutionary origin.     

Large accumulations of maize streak virus in the filter chamber and midgut cells of the leafhopper vector <Emphasis Type="Italic">Cicadulina mbila</Emphasis>

Maize streak virus (MSV, Mastrevirus, Geminiviridae) is persistently transmitted by Cicadulina mbila, apparently without propagation in its leafhopper vector. MSV was shown earlier by quantitative PCR to accumulate in the alimentary canal of C. mbila. We examined the alimentary canals of C. mbila leafhoppers that acquired MSV from diseased plants for various acquisition access periods (AAP) by immunofluorescence confocal laser scanning microscopy (iCLSM) and by immunogold labelling transmission electron microscopy (iTEM). Following a 7-day AAP and a 7-day inoculation period (IP) on healthy seedlings, MSV was detected by iCLSM mainly in the filter chamber and anterior midgut. Using iTEM, large accumulations of MSV particles, usually enclosed in membranous vesicles, were detected only in cells of the midgut, inside and outside the filter chamber, following 14- or 30-day AAPs, and also following 7-day AAP and 7-day IP on healthy plants. No virus was detected in the control non-vector species C. chinaï. Coated pits or vesicles, typical of clathrin-mediated endocytosis, were not observed. We discuss an alternative endocytosis pathway and suggest that the MSV accumulations are stored in endosomes in the midgut epithelial cells.     

Prolonged, but not acute, glutathione depletion promotes Fas-mediated mitochondrial permeability transition and apoptosis in mice

Glutathione depletion either decreased or increased death-receptor-mediated apoptosis in previous studies. Comparison of the durations of glutathione depletion before death-receptor stimulation in these studies might suggest a different effect of prolonged versus acute thiol depletion. We compared the effects of the prolonged glutathione depletion caused by a sulfur amino acid-deficient (SAA(-)) diet and the acute depletion caused by a single dose of phorone on hepatic apoptosis triggered by the administration of an agonistic anti-Fas antibody. The chronic SAA(-) diet did not affect hepatic Fas or Bcl-XL, but increased p53 and Bax, and exacerbated Fas-mediated mitochondrial membrane depolarization, electron-microscopy-proven outer mitochondrial membrane rupture, cytochrome c translocation to the cytosol, and caspase 3 activation. These effects were prevented by cyclosporin A, an inhibitor of mitochondrial permeability transition. The SAA(-) diet increased internucleosomal DNA fragmentation, the percentage of apoptotic hepatocytes, serum alanine transaminase (ALT) activity, and mortality after Fas stimulation. Despite a similar decrease in hepatic glutathione, administration of a single dose of phorone 1 hour before the anti-Fas antibody did not change p53 or Bax, and did not enhance Fas-induced mitochondrial permeability transition and toxicity. However, 4 repeated doses of phorone (causing more prolonged glutathione depletion) increased Bax and Fas-mediated toxicity. In conclusion, a chronic SAA(-) diet, but not acute phorone administration, increases p53 and Bax, and enhances Fas-induced mitochondrial permeability transition and apoptosis. Thiol depletion could cause oxidative stress that requires several hours to increase p53; the latter induces Bax, which translocates to mitochondria after Fas stimulation.     

Persistence of measles antibody after revaccination.

To evaluate persistence of measles antibody after revaccination, antibody levels were measured 6 years after revaccination of 40 hemagglutination-inhibition (HAI) antibody-negative students who had participated in a serosurvey in Massachusetts. Twelve subjects who had been HAI antibody-positive and were not revaccinated were included as a comparison group. Before revaccination, 7 revaccinees had no detectable plaque reduction neutralization (PRN) antibody (group 1) and 33 had low levels of PRN antibody (group 2). Three weeks after revaccination, all in group 1 and 30 (90%) of 33 in group 2 had developed a fourfold or greater rise in PRN antibody. Six years after revaccination, all subjects had PRN-detectable antibody. However, 12 in group 2 (36%) had antibody titers less than or equal to 1:120 compared with none in group 1 (P less than .01). Persons without PRN antibody will respond to revaccination and maintain protective antibody titers. In contrast, persons with low levels of PRN antibody may respond initially to revaccination, but their antibody titers may fall again to low levels.