Medications, particularly those that influence the serotonin system, are hypothesized to desensitize the fear network from the level of the amygdala through its projects to the hypothalamus and the brainstem. Effective psychosocial treatments may also reduce contextual fear and cognitive misattributions at the level of the prefrontal cortex and hippocampus. Neuroimaging studies should help clarify whether these hypotheses are correct.

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay -these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions.Experiments carried out over the past half century have revealed that neutrinos are found in three states, or flavors, and can transform from one flavor into another. These results indicate that each neutrino flavor state is a mixture of three different nonzero mass states, and to date offer the most compelling evidence for physics beyond the Standard Model. In a single experiment, LBNE will enable a broad exploration of the three-flavor model of neutrino physics with unprecedented detail. Chief among its potential discoveries is that of matter-antimatter asymmetries (through the mechanism of charge-parity violation) in neutrino flavor mixing -a step toward unraveling the mystery of matter generation in the early Universe. Independently, determination of the unknown neutrino mass ordering and precise measurement of neutrino mixing parameters by LBNE may reveal new fundamental symmetries of Nature.Grand Unified Theories, which attempt to describe the unification of the known forces, predict rates for proton decay that cover a range directly accessible with the next generation of large underground detectors such as LBNE's. The experiment's sensitivity to key proton decay channels will offer unique opportunities for the ground-breaking discovery of this phenomenon.Neutrinos emitted in the first few seconds of a core-collapse supernova carry with them the potential for great insight into the evolution of the Universe. LBNE's capability to collect and analyze this high-statistics neutrino signal from a supernova within our galaxy would provide a rare opportunity to peer inside a newly-formed neutron star and potentially witness the birth of a black hole.To achieve its goals, LBNE is conceived around three central components: (1) a new, highintensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a fine-grained near neutrino detector installed just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is ∼1,300 km from the neutrino source at Fermilab -a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions.With its exceptional combi...

Background Serotonin 1A receptors (5-HT1A) are implicated in major depressive disorder (MDD). We previously reported higher 5-HT1A binding potential (BPF=Bavail/KD) in antidepressant naïve MDD subjects compared to controls while other studies report lower BPND(BPND=fNDBavail/KD). Discrepancies can be related to differences in study population or methodology. We sought to replicate our findings in a novel cohort and determine whether choice of reference region and outcome measure could explain discrepancies. Methods Nine new controls and 22 new not recently medicated (4 years, NRM) MDD subjects underwent positron emission tomography with [11C]WAY100635. BPF and BPND were determined using a metabolite and free fraction corrected arterial input function. BPND was also determined using cerebellar gray matter (CGM) and cerebellar white matter (CWM) reference regions as input functions. Results BPF is higher in the new NRM cohort (p=0.037) compared to new controls, which is comparable to the effect in the previous cohort (p=0.04). We combined the cohorts to examine the effects of the reference region and outcome measure. In the combined cohort, BPF is higher in the NRM compared to controls (p=0.0001). Neither BPND using CWM (p=0.86) nor VT (p=0.374) differs between groups. When CGM is used, the NRM group has lower 5HT1A BPND compared with controls (p=0.03). CGM VT is higher in NRM compared to controls (p=0.007). Conclusions Choice of reference region and outcome measure can produce different 5-HT1A findings in MDD. Higher 5-HT1A BPF in MDD was found with the method with fewest assumptions about nonspecific binding and a reference region without receptors.

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