Genetic risk for aortic aneurysm in adolescent idiopathic scoliosis

BACKGROUND: Scoliosis is a feature of several genetic disorders that are also associated with aortic aneurysm, including Marfan syndrome, Loeys-Dietz syndrome, and type-IV Ehlers-Danlos syndrome. Life-threatening complications of aortic aneurysm can be decreased through early diagnosis. Genetic screening for mutations in populations at risk, such as patients with adolescent idiopathic scoliosis, may improve recognition of these disorders. METHODS: The coding regions of five clinically actionable genes associated with scoliosis (COL3A1, FBN1, TGFBR1, TGFBR2, and SMAD3) and aortic aneurysm were sequenced in 343 adolescent idiopathic scoliosis cases. Gene variants that had minor allele frequencies of <0.0001 or were present in human disease mutation databases were identified. Variants were classified as pathogenic, likely pathogenic, or variants of unknown significance. RESULTS: Pathogenic or likely pathogenic mutations were identified in 0.9% (three) of 343 adolescent idiopathic scoliosis cases. Two patients had pathogenic SMAD3 nonsense mutations consistent with type-III Loeys-Dietz syndrome and one patient had a pathogenic FBN1 mutation with subsequent confirmation of Marfan syndrome. Variants of unknown significance in COL3A1 and FBN1 were identified in 5.0% (seventeen) of 343 adolescent idiopathic scoliosis cases. Six FBN1 variants were previously reported in patients with Marfan syndrome, yet were considered variants of unknown significance based on the level of evidence. Variants of unknown significance occurred most frequently in FBN1 and were associated with greater curve severity, systemic features of Marfan syndrome, and joint hypermobility. CONCLUSIONS: Clinically actionable pathogenic mutations in genes associated with adolescent idiopathic scoliosis and aortic aneurysm are rare in patients with adolescent idiopathic scoliosis who are not suspected of having these disorders, although variants of unknown significance are relatively common. CLINICAL RELEVANCE: Routine genetic screening of all patients with adolescent idiopathic scoliosis for mutations in clinically actionable aortic aneurysm disease genes is not recommended on the basis of the high frequency of variants of unknown significance. Clinical evaluation and family history should heighten indications for genetic referral and testing

Enhanced response inhibition during intensive meditation training predicts improvements in self-reported adaptive socioemotional functioning.

We examined the impact of training-induced improvements in self-regulation, operationalized in terms of response inhibition, on longitudinal changes in self-reported adaptive socioemotional functioning. Data were collected from participants undergoing 3 months of intensive meditation training in an isolated retreat setting (Retreat 1) and a wait-list control group that later underwent identical training (Retreat 2). A 32-min response inhibition task (RIT) was designed to assess sustained self-regulatory control. Adaptive functioning (AF) was operationalized as a single latent factor underlying self-report measures of anxious and avoidant attachment, mindfulness, ego resilience, empathy, the five major personality traits (extroversion, agreeableness, conscientiousness, neuroticism, and openness to experience), diffi-culties in emotion regulation, depression, anxiety, and psychological well-being. Participants in Retreat 1 improved in RIT performance and AF over time whereas the controls did not. The control participants later also improved on both dimensions during their own retreat (Retreat 2). These improved levels of RIT performance and AF were sustained in follow-up assessments conducted approximately 5 months after the training. Longitudinal dynamic models with combined data from both retreats showed that improvement in RIT performance during training influenced the change in AF over time, which is consistent with a key claim in the Buddhist literature that enhanced capacity for self-regulation is an important precursor of changes in emotional well-being

Self-reported mindfulness and cortisol during a Shamatha meditation retreat.

Objective: Cognitive perseverations that include worry and rumination over past or future events may prolong cortisol release, which in turn may contribute to predisease pathways and adversely affect physical health. Meditation training may increase self-reported mindfulness, which has been linked to reductions in cognitive perseverations. However, there are no reports that directly link self-reported mindfulness and resting cortisol output. Here, the authors investigate this link. Methods: In an observational study, we measured self-reported mindfulness and p.m. cortisol near the beginning and end of a 3-month meditation retreat (N = 57). Results: Mindfulness increased from pre- to post-retreat, F(1, 56) = 36.20, p < .001. Cortisol did not significantly change. However, mindfulness was inversely related to p.m. cortisol at pre-retreat, r(53) = −.31, p < .05, and post-retreat, r(53) = −.30, p < .05, controlling for age and body mass index. Pre to postchange in mindfulness was associated with pre to postchange in p.m. cortisol, β = −.37, t(49) = 2.30, p < .05: Larger increases in mindfulness were associated with decreases in p.m. cortisol, whereas smaller increases (or slight decreases) in mindfulness were associated with an increase in p.m. cortisol. Conclusions: These data suggest a relation between self-reported mindfulness and resting output of the hypothalamic-pituitary-adrenal system. Future work should aim to replicate this finding in a larger cohort and determine stronger inference about causality by using experimental designs that include control-group conditions

A global collaboration to study intimate partner violence-related head trauma: The ENIGMA consortium IPV working group

Intimate partner violence includes psychological aggression, physical violence, sexual violence, and stalking from a current or former intimate partner. Past research suggests that exposure to intimate partner violence can impact cognitive and psychological functioning, as well as neurological outcomes. These seem to be compounded in those who suffer a brain injury as a result of trauma to the head, neck or body due to physical and/or sexual violence. However, our understanding of the neurobehavioral and neurobiological effects of head trauma in this population is limited due to factors including difficulty in accessing/recruiting participants, heterogeneity of samples, and premorbid and comorbid factors that impact outcomes. Thus, the goal of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium Intimate Partner Violence Working Group is to develop a global collaboration that includes researchers, clinicians, and other key community stakeholders. Participation in the working group can include collecting harmonized data, providing data for meta- and mega-analysis across sites, or stakeholder insight on key clinical research questions, promoting safety, participant recruitment and referral to support services. Further, to facilitate the mega-analysis of data across sites within the working group, we provide suggestions for behavioral surveys, cognitive tests, neuroimaging parameters, and genetics that could be used by investigators in the early stages of study design. We anticipate that the harmonization of measures across sites within the working group prior to data collection could increase the statistical power in characterizing how intimate partner violence-related head trauma impacts long-term physical, cognitive, and psychological health

Spatiospectral Decomposition of Multi-subject EEG: EvaluatingBlind Source Separation Algorithms on Real and RealisticSimulated Data

Electroencephalographic (EEG) oscillationspredominantly appear with periods between 1 s (1 Hz) and20 ms (50 Hz), and are subdivided into distinct frequencybands which appear to correspond to distinct cognitiveprocesses. A variety of blind source separation (BSS)approaches have been developed and implemented withinthe past few decades, providing an improved isolation ofthese distinct processes. Within the present study, wedemonstrate the feasibility of multi-subject BSS forderiving distinct EEG spatiospectral maps. Multi-subjectspatiospectral EEG decompositions were implementedusing the EEGIFT toolbox (http://mialab.mrn.org/software/eegift/) with real and realistic simulated datasets (thesimulation code is available at http://mialab.mrn.org/software/simeeg). Twelve different decomposition algorithmswere evaluated. Within the simulated data, WASOBI andCOMBI appeared to be the best performing algorithms, asthey decomposed the four sources across a range ofcomponent numbers and noise levels. RADICAL ICA,ERBM, INFOMAX ICA, ICA EBM, FAST ICA, andJADE OPAC decomposed a subset of sources within asmaller range of component numbers and noise levels.INFOMAX ICA, FAST ICA, WASOBI, and COMBIgenerated the largest number of stable sources within thereal dataset and provided partially distinct views ofunderlying spatiospectral maps. We recommend the multisubjectBSS approach and the selected algorithms for furtherstudies examining distinct spatiospectral networkswithin healthy and clinical populations.Keywords Blind source separation Multi-subjectdecomposition Resting EEG Simulated EEG Wavelets IC