A latent class analysis of parental bipolar disorder: examining associations with offspring psychopathology

Bipolar disorder (BD) is highly heterogeneous, and course variations are associated with patient outcomes. This diagnostic complexity challenges identification of patients in greatest need of intervention. Additionally, course variations have implications for offspring risk. First, latent class analysis (LCA) categorized parents with BD based on salient illness characteristics: BD type, onset age, polarity of index episode, pole of majority of episodes, rapid cycling, psychosis, anxiety comorbidity, and substance dependence. Fit indices favored three parental classes with some substantively meaningful patterns. Two classes, labeled “Earlier-Onset Bipolar-I” (EO-I) and “Earlier-Onset Bipolar-II” (EO-II), comprised parents who had a mean onset age in mid-adolescence, with EO-I primarily BD-I parents and EO-II entirely BD-II parents. The third class, labeled “Later-Onset BD” (LO) had an average onset age in adulthood. Classes also varied on probability of anxiety comorbidity, substance dependence, psychosis, rapid cycling, and pole of majority of episodes. Second, we examined rates of disorders in offspring (ages 4–33, Mage=13.46) based on parental latent class membership. Differences emerged for offspring anxiety disorders only such that offspring of EO-I and EO-II parents had higher rates, compared to offspring of LO parents, particularly for daughters. Findings may enhance understanding of BD and its nosologyThis study was funded by two Brain & Behavior Research Foundation (formerly NARSAD) Independent Investigator Awards (PI: Nierenberg), a Brain & Behavior Research Foundation Young Investigator Award (PI: Henin) generously supported in part by the SHINE Initiative, and an MGH Claflin Award (PI: Henin). We thank David A. Langer, Ph.D., Thomas M. Olino, Ph.D., and Meredith Lotz Wallace, Ph.D. for their consultation. (Brain & Behavior Research Foundation; Brain & Behavior Research Foundation Young Investigator Award; SHINE Initiative; MGH Claflin Award)Accepted manuscrip

Probing dark matter substructure in the gravitational lens HE0435-1223 with the WFC3 grism

Strong gravitational lensing provides a powerful test of Cold Dark Matter (CDM) as it enables the detection and mass measurement of low mass haloes even if they do not contain baryons. Compact lensed sources such as Active Galactic Nuclei (AGN) are particularly sensitive to perturbing subhalos, but their use as a test of CDM has been limited by the small number of systems which have significant radio emission which is extended enough avoid significant lensing by stars in the plane of the lens galaxy, and red enough to be minimally affected by differential dust extinction. Narrow-line emission is a promising alternative as it is also extended and, unlike radio, detectable in virtually all optically selected AGN lenses. We present first results from a WFC3 grism narrow-line survey of lensed quasars, for the quadruply lensed AGN HE0435-1223. Using a forward modelling pipeline which enables us to robustly account for spatial blending, we measure the [OIII] 5007 \AA~ flux ratios of the four images. We find that the [OIII] fluxes and positions are well fit by a simple smooth mass model for the main lens. Our data rule out a $M_{600}>10^{8} (10^{7.2}) M_\odot$ NFW perturber projected within $\sim$1\farcs0 (0\farcs1) arcseconds of each of the lensed images, where $M_{600}$ is the perturber mass within its central 600 pc. The non-detection is broadly consistent with the expectations of $\Lambda$CDM for a single system. The sensitivity achieved demonstrates that powerful limits on the nature of dark matter can be obtained with the analysis of $\sim20$ narrow-line lenses.Comment: Accepted for publication in MNRAS, 15 pages, 8 figure

The recency ratio is associated with reduced CSF glutamate in late-life depression

Glutamate is the principal excitatory neurotransmitter in the central nervous system, and is thought to be involved in the process of memory encoding and storage. Glutamate disturbances have also been reported in psychiatric disorders, such as schizophrenia and major depressive disorder (MDD), and in Alzheimer’s disease. In this paper, we set out to study the relationship between cerebrospinal fluid (CSF) glutamate levels and memory performance, which we believe has not been reported previously. In particular, we focused on recall performance broken down by serial position. Our prediction was that the recency ratio (Rr), a novel cognitive marker of intellectual impairment, would be linked with CSF glutamate levels. We studied data from a group of cognitively intact elderly individuals, 28 of whom had MDD, while 19 were controls. Study results indicated that Rr levels, but no other memory score, were inversely correlated with CSF glutamate levels, although this was found only in individuals with late-life MDD. For comparison, glutamine or GABA were not correlated with any memory performance measure

Hippocampus and basal forebrain volumes modulate effects of anticholinergic treatment on delayed recall in healthy older adults

Introduction Volumes of hippocampus and cholinergic basal forebrain are associated with delayed recall performance and may modulate the effect of a muscarinic receptor antagonist on delayed recall in healthy volunteers Methods We studied 15 older adults before and after the oral administration of a single dose of 1 or 2 mg of the preferential M1 muscarinic receptor antagonist trihexyphenidyl (Artane™) or placebo in a double-blind randomized cross-over design. Hippocampus and basal forebrain volumes were measured using magnetic resonance imaging. Results We found a significant interaction between treatment and hippocampus volume and a trend level effect between treatment and anterior basal forebrain volume on task performance, with an attenuation of the association between volume size and performance with trihexyphenidyl. Discussion These findings suggest a reduction of delayed recall performance with increasing doses of the muscarinic antagonist that is related to an uncoupling of the association of task performance with cholinergic basal forebrain and hippocampus volume

Cultivating equality: delivering just and sustainable food systems in a changing climate

T oday, the world faces a greater challenge perhaps than ever before: tackling hunger and malnutrition in the face of climate change and increasing natural resource scarcity. Civil society, governments, researchers, donors, and the private sector are simultaneously debating and collaborating to find solutions. But the dialogue is over-emphasizing food production. Improving yields is important, particularly in places where there is not enough food or where food producers live in poverty. But simply producing more is not enough to tackle hunger. Furthermore, acknowledging that lack of food is not the sole cause of hunger is important. Inequality shapes who has access to food and the resources to grow it and buy it. It governs who eats first and who eats worst. Inequality determines who can adapt more readily to a changing climate. Hunger and poverty are not an accident – they are the result of social and economic injustice and inequality at all levels, from household to global. The reality of inequality is no truer for anyone than it is for women – half the world’s population, with far less than their fair share of the world’s resources. If we are to achieve the new Sustainable Development Goal of ending hunger by 2030, we must address the underlying inequalities in food systems. In a changing climate, agriculture and food systems must be sustainable and productive – but our efforts cannot end there. They must be profitable for those for whom it is a livelihood; they must be equitable, to facilitate a level playing field in the market, to secure rights to resources for food producers, and to ensure access to nutritious food for all; they must be resilient to build the capacity of populations vulnerable to economic shocks, political instability, and increasing, climate-induced natural hazards to recover and still lift themselves out of poverty

Increased levels of ascorbic acid in the cerebrospinal fluid of cognitively intact patients with major depression: a preliminary study

Major depressive disorder (MDD) in the elderly is a risk factor for dementia, but the precise biological basis remains unknown, hampering the search for novel biomarkers and treatments. In this study, we performed metabolomics analysis of cerebrospinal fluid (CSF) from cognitively intact elderly patients (N = 28) with MDD and age- and gender-matched healthy controls (N = 18). The CSF levels of 177 substances were measured, while 288 substances were below the detection limit. Only ascorbic acid was significantly different, with higher levels in the MDD group at baseline. There were no correlations between CSF ascorbic acid levels and clinical variables in MDD patients at baseline. At the 3-year follow-up, there was no difference of CSF ascorbic acid levels between two groups. There was a negative correlation between CSF ascorbic acid and CSF amyloid-β42 levels in all subjects. However, there were no correlations between ascorbic acid and other biomarkers (e.g., amyloid-β40, total and phosphorylated tau protein). This preliminary study suggests that abnormalities in the transport and/or release of ascorbic acid might play a role in the pathogenesis of late-life depression

Patient-powered research networks: building capacity for conducting patient-centered clinical outcomes research.

The Patient-Centered Outcomes Research Institute (PCORI) recently launched PCORnet to establish a single inter-operable multicenter data research network that will support observational research and randomized clinical trials. This paper provides an overview of the patient-powered research networks (PPRNs), networks of patient organizations focused on a particular health condition that are interested in sharing health information and engaging in research. PPRNs will build on their foundation of trust within the patient communities and draw on their expertise, working with participants to identify true patient-centered outcomes and direct a patient-centered research agenda. The PPRNs will overcome common challenges including enrolling a diverse and representative patient population; engaging patients in governance; designing the data infrastructure; sharing data securely while protecting privacy; prioritizing research questions; scaling small networks into a larger network; and identifying pathways to sustainability. PCORnet will be the first distributed research network to bring PCOR to national scale

Basal Forebrain Mediated Increase in Brain CRF is Associated with Increased Cholinergic Tone and Depression

Major depression is a devastating disease that generates significant suffering and cost. After controlling for the main effects of diagnosis and Cerebrospinal Fluid Corticotropin-Releasing Factor (CSF CRF), the interaction between CSF CRF and major depression disorder diagnosis was a significant predictor of basal forebrain cholinergic nuclei volume, but not of hippocampal volume. By investigating both markers concurrently in participants with and without depression, we describe the extent to which the interaction between CSF CRF levels and depression diagnosis is associated with the volume of the forebrain cholinergic nuclei and of the hippocampus. These results contribute to our understanding of the role of brain’s stress axis in depression

Properties of satellite galaxies in the SDSS photometric survey: luminosities, colours and projected number density profiles

We analyze photometric data in SDSS-DR7 to infer statistical properties of faint satellites associated to isolated bright galaxies (M_r<-20.5) in the redshift range 0.03<z<0.1. The mean projected radial profile shows an excess of companions in the photometric sample around the primaries, with approximately a power law shape that extends up to ~700kpc. Given this overdensity signal, a suitable background subtraction method is used to study the statistical properties of the population of bound satellites, down to magnitude M_r=-14.5, in the projected radial distance range 100 < r_p/kpc < 3 R_{vir}. We have also considered a color cut consistent with the observed colors of spectroscopic satellites in nearby galaxies so that distant redshifted galaxies do not dominate the statistics. We have tested the implementation of this procedure using a mock catalog. We find that the method is effective in reproducing the true projected radial satellite number density profile and luminosity distributions, providing confidence in the results derived from SDSS data. The spatial extent of satellites is larger for bright, red primaries. Also, we find a larger spatial distribution of blue satellites. For the different samples analyzed, we derive the average number of satellites and their luminosity distributions down to M_r=-14.5. The mean number of satellites depends very strongly on host luminosity. Bright primaries (M_r<-21.5) host on average ~6 satellites with M_r<-14.5, while primaries with -21.5<M_r<-20.5 have less than 1 satellite per host. We provide Schechter function fits to the luminosity distributions of satellite galaxies with faint-end slopes -1.3+/-0.2. This shows that satellites of bright primaries lack an excess population of faint objects, in agreement with the results in the Milky Way and nearby galaxies.Comment: 14 pages, 13 figures. Accepted for publication in Astronomical Journa