Altered interaction with environmental reinforcers in major depressive disorder: Relationship to anhedonia

Anhedonia—defined as loss of interest or pleasure—is one of two core symptoms of major depressive disorder (MDD). Anhedonia may involve decreased enjoyment of potentially rewarding activities and decreased motivation to engage in such activities. Increased engagement with reinforcers—activities with the potential to be positive experiences—is a frequent target of cognitive-behavioral therapies. Nevertheless, how environmental reinforcers are perceived, and how decisions to approach or avoid them are made by individuals with MDD, is largely unknown. We developed an experimental Behavioral Approach Motivation Paradigm to study how activities are evaluated and approached in MDD. Twenty-one MDD participants and 23 healthy controls performed an experimental task that rated activity words for their hedonic value, then engaged in an approach-avoidance joystick task with each individual’s unique set of ‘liked’ and ‘disliked’ activity words. A negative correlation was observed between anhedonia and the number of ‘liked’ activities across participants. No significant difference between approach and avoidance behavior was found in direct comparisons between healthy controls and MDD participants; however, weaker avoidance and greater approach toward ‘disliked’ activities was found in MDD participants. This suggests negative bias in selecting environmental opportunities, potentially further compromising access to hedonic experiences in MDD

Ketamine and Attentional Bias Toward Emotional Faces: Dynamic Causal Modeling of Magnetoencephalographic Connectivity in Treatment-Resistant Depression

The glutamatergic modulator ketamine rapidly reduces depressive symptoms in individuals with treatment-resistant major depressive disorder (TRD) and bipolar disorder. While its underlying mechanism of antidepressant action is not fully understood, modulating glutamatergically-mediated connectivity appears to be a critical component moderating antidepressant response. This double-blind, crossover, placebo-controlled study analyzed data from 19 drug-free individuals with TRD and 15 healthy volunteers who received a single intravenous infusion of ketamine hydrochloride (0.5 mg/kg) as well as an intravenous infusion of saline placebo. Magnetoencephalographic recordings were collected prior to the first infusion and 6–9 h after both drug and placebo infusions. During scanning, participants completed an attentional dot probe task that included emotional faces. Antidepressant response was measured across time points using the Montgomery-Asberg Depression Rating Scale (MADRS). Dynamic causal modeling (DCM) was used to measure changes in parameter estimates of connectivity via a biophysical model that included realistic local neuronal architecture and receptor channel signaling, modeling connectivity between the early visual cortex, fusiform cortex, amygdala, and inferior frontal gyrus. Clinically, ketamine administration significantly reduced depressive symptoms in TRD participants. Within the model, ketamine administration led to faster gamma aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) transmission in the early visual cortex, faster NMDA transmission in the fusiform cortex, and slower NMDA transmission in the amygdala. Ketamine administration also led to direct and indirect changes in local inhibition in the early visual cortex and inferior frontal gyrus and to indirect increases in cortical excitability within the amygdala. Finally, reductions in depressive symptoms in TRD participants post-ketamine were associated with faster α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) transmission and increases in gain control of spiny stellate cells in the early visual cortex. These findings provide additional support for the GABA and NMDA inhibition and disinhibition hypotheses of depression and support the role of AMPA throughput in ketamine's antidepressant effects.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT00088699?term=NCT00088699&draw=2&rank=1, identifier NCT00088699

Effects of arterial cannulation stress on regional cerebral blood flow in major depressive disorder

Individuals with major depressive disorder (MDD) display abnormal neurophysiological responses to psychological stress but little is known about their neurophysiological responses to physiological stressors. Using [15O-H2O] positron emission tomography we assessed whether the regional cerebral blood flow (rCBF) response to arterial cannulation differed between patients with MDD and healthy controls (HCs). Fifty-one MDD patients and 62 HCs were scanned following arterial cannulation and 15 MDD patients and 17 HCs were scanned without arterial cannulation. A region-of-interest analysis showed that a significantly increased rCBF of the anterior cingulate cortex and right amygdala was associated with arterial cannulation in MDD. A whole brain analysis showed increased rCBF of the right post-central gyrus, left temporopolar cortex, and right amygdala during arterial cannulation in MDD patients. The rCBF in the right amygdala was significantly correlated with depression severity. Conceivably, the limbic response to invasive physical stress is greater in MDD subjects than in HCs

Cloud System Evolution in the Trades (CSET): Following the Evolution of Boundary Layer Cloud Systems with the NSFNCAR GV

The Cloud System Evolution in the Trades (CSET) study was designed to describe and explain the evolution of the boundary layer aerosol, cloud, and thermodynamic structures along trajectories within the North Pacific trade winds. The study centered on seven round trips of the National Science FoundationNational Center for Atmospheric Research (NSFNCAR) Gulfstream V (GV) between Sacramento, California, and Kona, Hawaii, between 7 July and 9 August 2015. The CSET observing strategy was to sample aerosol, cloud, and boundary layer properties upwind from the transition zone over the North Pacific and to resample these areas two days later. Global Forecast System forecast trajectories were used to plan the outbound flight to Hawaii with updated forecast trajectories setting the return flight plan two days later. Two key elements of the CSET observing system were the newly developed High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Cloud Radar (HCR) and the high-spectral-resolution lidar (HSRL). Together they provided unprecedented characterizations of aerosol, cloud, and precipitation structures that were combined with in situ measurements of aerosol, cloud, precipitation, and turbulence properties. The cloud systems sampled included solid stratocumulus infused with smoke from Canadian wildfires, mesoscale cloudprecipitation complexes, and patches of shallow cumuli in very clean environments. Ultraclean layers observed frequently near the top of the boundary layer were often associated with shallow, optically thin, layered veil clouds. The extensive aerosol, cloud, drizzle, and boundary layer sampling made over open areas of the northeast Pacific along 2-day trajectories during CSET will be an invaluable resource for modeling studies of boundary layer cloud system evolution and its governing physical processes

The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

Epigenomeâ wide association of PTSD from heterogeneous cohorts with a common multiâ site analysis pipeline

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138305/1/ajmgb32568.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138305/2/ajmgb32568_am.pd

Track Finding Efficiency in BaBar

We describe several studies to measure the charged track reconstruction efficiency and asymmetry of the BaBar detector. The first two studies measure the tracking efficiency of a charged particle using $\tau$ and initial state radiation decays. The third uses the $\tau$ decays to study the asymmetry in tracking, the fourth measures the tracking efficiency for low momentum tracks, and the last measures the reconstruction efficiency of $K_S^0$ particles. The first section also examines the stability of the measurements vs BaBar running periods.Comment: 20 pages, 30 figures, Submitted to Nuclear Instruments and Methods in Physics Research

Introduced deer and their potential role in disease transmission to livestock in Australia

1. The transmission of pathogens between wildlife and livestock is a globally recognised threat to the livestock industry, as well as to human and wildlife health. Wild cervids are susceptible to many diseases affecting livestock. This presents a challenge for wildlife and domestic animal disease management because the frequent use of agricultural areas by wild cervids may hamper the effectiveness of disease control strategies. 2. Six deer species have established wild populations in Australia and are expanding in range and abundance. A comprehensive literature review of diseases impacting deer and livestock was undertaken, resulting in consideration of 38 pathogens. A qualitative risk assessment was then carried out to assess the overall risk posed by the pathogens to the livestock industry. 3. Five diseases (bovine tuberculosis, foot and mouth disease, malignant catarrhal fever, surra, and screw‐worm fly infestation) ranked highly in our risk assessment. Of these five diseases, only one (malignant catarrhal fever) is currently present in Australia, but all five are notifiable diseases at a national level. Data on these diseases in deer are limited, especially for one of the most abundant species, the sambar deer Rusa unicolor, highlighting a further potential risk attributable to a lack of understanding of disease epidemiology. 4. This paper provides a detailed review of the pathogens affecting both cervids and livestock in Australia, and applies a qualitative framework for assessing the risk posed by deer to the livestock industry. The qualitative framework used here could easily be adapted to assess disease risk in other contexts, making this work relevant to scientists and wildlife managers, as well as to livestock industry workers, worldwide

Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table