Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

BACKGROUND—Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)–Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS—We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS—In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen’s d = −0.17, p = .00054), and smaller amygdalae (d = −0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p \u3c .0063). CONCLUSIONS—Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain’s response to trauma

Diverging volumetric trajectories following pediatric traumatic brain injury.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2-5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2-5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory

Functional Brain Hyperactivations Are Linked to an Electrophysiological Measure of Slow Interhemispheric Transfer Time after Pediatric Moderate/Severe Traumatic Brain Injury.

Increased task-related blood oxygen level dependent (BOLD) activation is commonly observed in functional magnetic resonance imaging (fMRI) studies of moderate/severe traumatic brain injury (msTBI), but the functional relevance of these hyperactivations and how they are linked to more direct measures of neuronal function remain largely unknown. Here, we investigated how working memory load (WML)-dependent BOLD activation was related to an electrophysiological measure of interhemispheric transfer time (IHTT) in a sample of 18 msTBI patients and 26 demographically matched controls from the UCLA RAPBI (Recovery after Pediatric Brain Injury) study. In the context of highly similar fMRI task performance, a subgroup of TBI patients with slow IHTT had greater BOLD activation with higher WML than both healthy control children and a subgroup of msTBI patients with normal IHTT. Slower IHTT treated as a continuous variable was also associated with BOLD hyperactivation in the full TBI sample and in controls. Higher WML-dependent BOLD activation was related to better performance on a clinical cognitive performance index, an association that was more pronounced within the patient group with slow IHTT. Our previous work has shown that a subgroup of children with slow IHTT after pediatric msTBI has increased risk for poor white matter organization, long-term neurodegeneration, and poor cognitive outcome. BOLD hyperactivations after msTBI may reflect neuronal compensatory processes supporting higher-order capacity demanding cognitive functions in the context of inefficient neuronal transfer of information. The link between BOLD hyperactivations and slow IHTT adds to the multi-modal validation of this electrophysiological measure as a promising biomarker

Adaptive Identification of Cortical and Subcortical Imaging Markers of Early Life Stress and Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is a heterogeneous condition associated with a range of brain imaging abnormalities. Early life stress (ELS) contributes to this heterogeneity, but we do not know how a history of ELS influences traditionally defined brain signatures of PTSD. Here, we used a novel machine learning method – evolving partitions to improve classification (EPIC) – to identify shared and unique structural neuroimaging markers of ELS and PTSD in 97 combat-exposed military veterans. METHODS: We used EPIC with repeated cross-validation (CV) to determine how combinations of cortical thickness, surface area, and subcortical brain volumes could contribute to classification of PTSD (n = 40) versus controls (n = 57), and classification of ELS within the PTSD (ELS+ n = 16; ELS− n = 24) and control groups (ELS+ n = 16; ELS− n = 41). Additional inputs included intracranial volume, age, sex, adult trauma, and depression. RESULTS: On average, EPIC classified PTSD with 69% accuracy (SD = 5%), and ELS with 64% accuracy in the PTSD group (SD = 10%), and 62% accuracy in controls (SD = 6%). EPIC selected unique sets of individual features that classified each group with 75–85% accuracy in post hoc analyses; combinations of regions marginally improved classification from the individual atlas-defined brain regions. Across analyses, surface area in the right posterior cingulate was the only variable that was repeatedly selected as an important feature for classification of PTSD and ELS. CONCLUSIONS: EPIC revealed unique patterns of features that distinguished PTSD and ELS in this sample of combat-exposed military veterans, which may represent distinct biotypes of stress-related neuropathology

Preventing Pandemics via International Development: A Systems Approach

Tiffany Bogich and colleagues find that breakdown or absence of public health infrastructure is most often the driver in pandemic outbreaks, whose prevention requires mainstream development funding rather than emergency funding

THE K2 M67 STUDY: REVISITING OLD FRIENDS WITH K2 REVEALS OSCILLATING RED GIANTS IN THE OPEN CLUSTER M67

Observations of stellar clusters have had a tremendous impact in forming our understanding of stellar evolution. The open cluster M67 has a particularly important role as a calibration benchmark for stellar evolution theory due to its near-solar composition and age. As a result, it has been observed extensively, including attempts to detect solar-like oscillations in its main sequence and red giant stars. However, any asteroseismic inference has so far remained elusive due to the difficulty in measuring these extremely low-amplitude oscillations. Here we report the first unambiguous detection of solar-like oscillations in the red giants of M67. We use data from the Kepler ecliptic mission, K2, to measure the global asteroseismic properties. We find a model-independent seismic-informed distance of 816 ±11 pc, or (m - M)0 = 9.57 ± 0.03 mag, an average red giant mass of 1.36 ± 0.01 M⊙, in agreement with the dynamical mass from an eclipsing binary near the cluster turn-off, and ages of individual stars compatible with isochrone fitting. We see no evidence of strong mass loss on the red giant branch. We also determine seismic of all the cluster giants with a typical precision of ∼0.01 dex. Our results generally show good agreement with independent methods and support the use of seismic scaling relations to determine global properties of red giant stars with near-solar metallicity. We further illustrate that the data are of such high quality that future work on individual mode frequencies should be possible, which would extend the scope of seismic analysis of this cluster

Bryozoan genera Fenestrulina and Microporella no longer confamilial; multi-gene phylogeny supports separation

Bryozoans are a moderately diverse, mostly marine phylum with a fossil record extending to the early Ordovician. Compared to other phyla, little is known about their phylogenetic relationships at both lower and higher taxonomic levels. Hence, an effort is being made to elucidate the phylogenetic relationships among bryozoans. Here, we present newly sequenced nuclear and mitochondrial genes for 21 cheilostome bryozoans and compile these with existing orthologous molecular data. Using these data, we focus on reconstructing the phylogenetic relationships of Fenestrulina and Microporella, two species-rich genera. They are currently placed in a globally distributed family, Microporellidae, defined by having a semicircular primary orifice and a proximal ascopore, although there are indirect inferences in the morphological literature that suggest they might not be confamilial. Our six-gene phylogenetic analysis reveals that the genera Fenestrulina and Microporella are each monophyletic, with the sister clade to Microporella comprising non-microporellids. These genera thus have a polyphyletic relationship and should not be placed in the same family. Our result supports the reinstatement of the family Fenestrulinidae Jullien, 1888 for Fenestrulina and genera with comparable frontal shield and ooecial morphologies. Our well-supported phylogeny based on independent molecular data lends credit to existing phylogenetic hypotheses based on morphological observations but does not conform to the current classification of these particular bryozoans. This illustrates the general need for a rethink of bryozoan higher-level systematics, ideally based on both morphological and molecular data

Replication of an emergency department-based recovery coaching intervention and pilot testing of pragmatic trial protocols within the context of Indiana's Opioid State Targeted Response plan

Solving the opioid crisis requires immediate, innovative, and sustainable solutions. A number of promising strategies are being carried out by U.S. states and territories as part of their Opioid State Targeted Response (STR) plans funded through the 21st Century Cures Act, and they provide an opportunity for researchers to assess effectiveness of these interventions using pragmatic approaches. This paper describes a pilot study of Project Planned Outreach, Intervention, Naloxone, and Treatment (POINT), the intervention that served as the basis for Indiana's STR-funded, emergency department (ED)-based peer specialist expansion that was conducted in preparation for a larger, multisite pragmatic trial. Through the pilot, we identified, documented, and corrected for challenges encountered while implementing planned study protocols. Per the project's funding mechanism, the ability to move to the larger trial was determined by the achievement of 3 milestones: (1) successful replication of the intervention; (2) demonstrated ability to obtain the necessary sample size; and (3) observe a higher level of engagement in medication for addiction treatment in the POINT group compared to standard care. Overall implementation of the study protocols was successful, with only minor refinements to proposed procedures being required in light of challenges with (1) data access, (2) recruitment, and (3) identification of the expansion hospitals. All three milestones were reached. Challenges in implementing protocols and reaching milestones resulted in refinements that improved the study design overall. The subsequent trial will add to the limited but growing evidence on ED-based peer supports. Capitalizing on STR efforts to study an already scaling and promising intervention is likely to lead to faster and more sustainable results with greater generalizability than traditional, efficacy-focused clinical research

Maternal psychological distress in primary care and association with child behavioural outcomes at age three

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers’ mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0777-2) contains supplementary material, which is available to authorized users