We discuss the strategies employed in data quality control and quality assurance for the cognitive core of Neurobiological Predictors of Huntington's Disease (PREDICT-HD), a long-term observational study of over 1,000 participants with prodromal Huntington disease. In particular, we provide details regarding the training and continual evaluation of cognitive examiners, methods for error corrections, and strategies to minimize errors in the data. We present five important lessons learned to help other researchers avoid certain assumptions that could potentially lead to inaccuracies in their cognitive data.
Young adults with psychiatric illnesses are more likely to use cannabis and experience problems from use. It is not known whether those with a lifetime psychiatric illness experience a prolonged cannabis withdrawal syndrome with abstinence. Participants were fifty young adults, aged 18-25, recruited from the Boston-area in 2015-2016, who used cannabis at least weekly, completed the Structured Clinical Interview for DSM-IV to identify Axis I psychiatric diagnoses (PD+ vs PD-), and attained cannabis abstinence with a four-week contingency management protocol. Withdrawal symptom severity was assessed at baseline and at four weekly abstinent visits using the Cannabis Withdrawal Scale. Cannabis dependence, age of initiation, and rate of abstinence were similar in PD+ and PD- groups. There was a diagnostic group by abstinent week interaction, suggesting a difference in time course for resolution of withdrawal symptoms by group, F(4,46)=3.8, p=0.009, controlling for sex, baseline depressive and anxiety symptoms, and frequency of cannabis use in the prior 90days. In post hoc analyses, there was a difference in time-course of cannabis withdrawal. PD- had significantly reduced withdrawal symptom severity in abstinent week one [t(46)=-2.2, p=0.03], while PD+ did not report improved withdrawal symptoms until the second abstinent week [t(46)=-4.1, p=0.0002]. Cannabis withdrawal symptoms improved over four weeks in young people with and without a lifetime psychiatric diagnosis. However, those with a psychiatric illness reported one week delayed improvement in withdrawal symptom severity. Longer duration of cannabis withdrawal may be a risk factor for cannabis dependence and difficulty quitting.
People seek weight loss support on online social networks, but little is known about how to build a supportive community. We created four Twitter accounts portraying women interested in weight loss (two obese, two normal weight/overweight) and followed health care professional and peer accounts for 2-5 weeks. We examined follow back rates, interactions, and organic follows from professionals and peers by weight status. Follow back rates did not differ by weight status when following professionals (6.8 % normal weight/overweight vs 11.0 % for obese; p = 0.4167) or peers (6.7 % for normal weight/overweight vs 10.8 % for obese; p = 0.1548). Number of interactions and organic followers also did not differ by weight status. Peers interacted with study accounts significantly more than professionals (p = 0.0138), but interactions were infrequent. Women seeking weight loss support on Twitter may need to be present for more than 5 weeks to build an interactive weight loss community.
Perinatal mood and anxiety disorders are among the most common mental health conditions encountered by women of reproductive age. When left untreated, perinatal mood and anxiety disorders can have profound adverse effects on women and their children, ranging from increased risk of poor adherence to medical care, exacerbation of medical conditions, loss of interpersonal and financial resources, smoking and substance use, suicide, and infanticide. Perinatal mood and anxiety disorders are associated with increased risks of maternal and infant mortality and morbidity and are recognized as a significant patient safety issue. In 2015, the Council on Patient Safety in Women's Health Care convened an interdisciplinary workgroup to develop an evidence-based patient safety bundle to address maternal mental health. The focus of this bundle is perinatal mood and anxiety disorders. The bundle is modeled after other bundles released by the Council on Patient Safety in Women's Health Care and provides broad direction for incorporating perinatal mood and anxiety disorder screening, intervention, referral, and follow-up into maternity care practice across health care settings. This commentary provides information to assist with bundle implementation.
Quantitative EEG during normal aging: association with the Alzheimer's disease genetic risk variant in PICALM gene
Genome-wide association studies have identified novel risk variants for Alzheimer's disease (AD). Among these, a gene carrying one of the highest risks for AD is PICALM. The PICALM rs3851179 A allele is thought to have a protective effect, whereas the G allele appears to confer risk for AD. The influence of the PICALM genotype on brain function in nondemented subjects remains largely unknown. We examined the possible effect of the PICALM rs3851179 genotype on quantitative electroencephalography recording at rest in 137 nondemented volunteers (age range: 20-79 years) subdivided into cohorts of those younger than and those older than 50 years of age. The homozygous presence of the AD risk variant PICALM GG was associated with an increase in beta relative power, with the effect being more pronounced in the older cohort. Beta power elevation in resting-state electroencephalography has previously been linked to cortical disinhibition and hyperexcitability. The increase in beta relative power in the carriers of the AD risk PICALM GG genotype suggests changes in the cortical excitatory-inhibitory balance, which are heightened during normal aging.
Supervisor and Organizational Factors Associated with Supervisor Support of Job Accommodations for Low Back Injured Workers
Purpose Temporary job accommodations contribute to the prevention of chronic work disability due to low back pain (LBP) through the facilitation of early return to work; yet, workplace dimensions of job accommodation are poorly understood. The objective of this study was to determine supervisor and organizational factors associated with supervisors' support for temporary job accommodations for LBP injured workers. Methods Supervisors were recruited from 19 workplaces in the USA and Canada and completed an online survey regarding job accommodation practices and potential associated factors with respect to a case vignette of a worker with LBP. Multivariable linear regression was used to identify the most parsimonious set of factors associated with supervisors' support for accommodations. Results A total of 804 supervisors participated with 796 eligible for inclusion in the analysis. The final set of factors explained 21 % of the variance in supervisors' support for temporary job accommodations. Considerate leadership style (beta = 0.261; 95 % CI 0.212, 0.310), workplace disability management policies and practices (beta = 0.243; 95 % CI 0.188, 0.298), and supervisor autonomy for designing and providing workplace accommodations (beta = 0.156; 95 % CI 0.071, 0.241) had the largest effect on supervisor support for accommodations. Conclusion Factors predicting supervisors' likelihood to accommodate LBP injured workers include use of considerate leadership style, workplace disability management policies and practices, and supervisor autonomy. Workplace interventions targeting these factors should be developed and evaluated for their ability to improve work disability prevention outcomes.
OBJECTIVE: There is an evolving debate about pathological affective responses in patients with anorexia nervosa (AN). We examined startle responses in different stages of AN.
METHODS: We applied a startle reflex paradigm with standardized visual stimuli (International Affective Pictures System; food and body pictures) in 64 female participants (17 acute AN, 16 chronically ill AN, 15 long-term recovered AN, 16 healthy controls). We measured subjective ratings of valence and anxiety, and electromyographic startle responses.
RESULTS: Participants with acute and chronic AN displayed the same subjective valence ratings to affective stimuli but showed less startle reactivity to affective pictures (F(6, 116) = 2.75, p = .02) compared with healthy control. Food pictures were rated as more unpleasant and higher anxiety provoking by currently ill AN (F(3, 59) = 3.32, p=.03).
DISCUSSION: We observed diverging subjective and psychophysiological reactions in different stages of AN. Psychophysiological methods can help to attain a more comprehensive understanding of biological alterations in the long-term course of AN.
We provide three examples of how addiction stigma is sanctioned: (a) discrimination against people with addictions is often legal; (b) public health communications frequently use stigma to promote prevention; (c) some programmes, such as '12 steps' promote self-stigma. The implications of sanctioned stigma for stigma-change programmes are then discussed.
Impaired cue identification and intention retrieval underlie prospective memory deficits in patients with first-episode schizophrenia
OBJECTIVE: Schizophrenia is associated with impairment in prospective memory, the ability to remember to carry out an intended action in the future. It has been established that cue identification (detection of the cue event signaling that an intended action should be performed) and intention retrieval (retrieval of an intention from long-term memory following the recognition of a prospective cue) are two important processes underlying prospective memory. The purpose of this study was to examine prospective memory deficit and underlying cognitive processes in patients with first-episode schizophrenia.
METHODS: This study examined cue identification and intention retrieval components of event-based prospective memory using a dual-task paradigm in 30 patients with first-episode schizophrenia and 30 healthy controls. All participants were also administered a set of tests assessing working memory and retrospective memory.
RESULTS: Both cue identification and intention retrieval were impaired in patients with first-episode schizophrenia compared with healthy controls ( ps < 0.05), with a large effect size for cue identification (Cohen's d = 0.98) and a medium effect size for intention retrieval (Cohen's d = 0.62). After controlling for working memory and retrospective memory, the difference in cue identification between patients and healthy controls remained significant. However, the difference in intention retrieval between the two groups was no longer significant. In addition, there was a significant inverse relationship between cue identification and negative symptoms ( r = -0.446, p = 0.013) in the patient group.
CONCLUSION: These findings suggest that both cue identification and intention retrieval in event-based prospective memory are impaired in patients with first-episode schizophrenia. Cue identification and intention retrieval could be potentially used as biomarkers for early detection and treatment prognosis of schizophrenia. In addition, addressing cue identification deficit through cognitive enhancement training may potentially improve negative symptoms as well.
Using Factor Mixture Models to Evaluate the Type A/B Classification of Alcohol Use Disorders in a Heterogeneous Treatment Sample
BACKGROUND: The type A/B classification model for alcohol use disorders (AUDs) has received considerable empirical support. However, few studies examine the underlying latent structure of this subtyping model, which has been challenged as a dichotomization of a single drinking severity dimension. Type B, relative to type A, alcoholics represent those with early age of onset, greater familial risk, and worse outcomes from alcohol use.
METHOD: We examined the latent structure of the type A/B model using categorical, dimensional, and factor mixture models in a mixed gender community treatment-seeking sample of adults with an AUD.
RESULTS: Factor analytic models identified 2-factors (drinking severity/externalizing psychopathology and internalizing psychopathology) underlying the type A/B indicators. A factor mixture model with 2-dimensions and 3-classes emerged as the best overall fitting model. The classes reflected a type A class and two type B classes (B1 and B2) that differed on the respective level of drinking severity/externalizing pathology and internalizing pathology. Type B1 had a greater prevalence of women and more internalizing pathology and B2 had a greater prevalence of men and more drinking severity/externalizing pathology. The 2-factor, 3-class model also exhibited predictive validity by explaining significant variance in 12-month drinking and drug use outcomes.
CONCLUSIONS: The model identified in the current study may provide a basis for examining different sources of heterogeneity in the course and outcome of AUDs.
Use of Veterans Health Administration Mental Health and Substance Use Disorder Treatment After Exiting Prison: The Health Care for Reentry Veterans Program
The Veterans Health Administration (VA) Health Care for Reentry Veterans (HCRV) program links veterans exiting prison with treatment. Among veterans served by HCRV, national VA clinical data were used to describe contact with VA health care, and mental health and substance use disorder diagnoses and treatment use. Of veterans seen for an HCRV outreach visit, 56 % had contact with VA health care. Prevalence of mental health disorders was 57 %; of whom 77 % entered mental health treatment within a month of diagnosis. Prevalence of substance use disorders was 49 %; of whom 37 % entered substance use disorder treatment within a month of diagnosis. For veterans exiting prison, increasing access to VA health care, especially for rural veterans, and for substance use disorder treatment, are important quality improvement targets.
Using Getting To Outcomes to facilitate the use of an evidence-based practice in VA homeless programs: a cluster-randomized trial of an implementation support strategy
BACKGROUND: Incorporating evidence-based integrated treatment for dual disorders into typical care settings has been challenging, especially among those serving Veterans who are homeless. This paper presents an evaluation of an effort to incorporate an evidence-based, dual disorder treatment called Maintaining Independence and Sobriety Through Systems Integration, Outreach, and Networking-Veterans Edition (MISSION-Vet) into case management teams serving Veterans who are homeless, using an implementation strategy called Getting To Outcomes (GTO).
METHODS: This Hybrid Type III, cluster-randomized controlled trial assessed the impact of GTO over and above MISSION-Vet Implementation as Usual (IU). Both conditions received standard MISSION-Vet training and manuals. The GTO group received an implementation manual, training, technical assistance, and data feedback. The study occurred in teams at three large VA Medical Centers over 2 years. Within each team, existing sub-teams (case managers and Veterans they serve) were the clusters randomly assigned. The trial assessed MISSION-Vet services delivered and collected via administrative data and implementation barriers and facilitators, via semi-structured interview.
RESULTS: No case managers in the IU group initiated MISSION-Vet while 68% in the GTO group did. Seven percent of Veterans with case managers in the GTO group received at least one MISSION-Vet session. Most case managers appreciated the MISSION-Vet materials and felt the GTO planning meetings supported using MISSION-Vet. Case manager interviews also showed that MISSION-Vet could be confusing; there was little involvement from leadership after their initial agreement to participate; the data feedback system had a number of difficulties; and case managers did not have the resources to implement all aspects of MISSION-Vet.
CONCLUSIONS: This project shows that GTO-like support can help launch new practices but that multiple implementation facilitators are needed for successful execution of a complex evidence-based program like MISSION-Vet.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01430741.
Alterations of the topological organization of abnormal regions or network-level structural aberrations are still poorly understood for post-traumatic stress disorder (PTSD). Herein, we investigated brain structural networks in recent-onset PTSD patients, all affected by the coalmine-flood disaster. Cortical networks were studied in recent onset PTSD patients (n = 15) and matched healthy controls (n = 25). Cortical networks were constructed by thresholding correlation matrices of 150 regions and quantified using graph theoretical approaches. Contributions of high-degree nodes, and regional and global network measures, including degree and betweenness, were studied. Compared with healthy controls, PTSD patients showed altered quantitative values in global network properties, characterized by shorter path length and higher clustering. Moreover, PTSD patients exhibited decreased connectivity in the right lingual gyrus, parahippocampal gyrus, left supramarginal gyrus, parahippocampal gyrus, bilateral superior and inferior frontal gyrus, superior frontal gyrus, and posterior cingulate gyrus. Nodal centrality decreased predominantly in the occipital regions (lingual gyrus) and default-mode regions, while increased correlations and centralities were observed in the medial temporal lobe and posterior cingulate cortex. PTSD-related networks exhibited a less efficient organization and regional connectivity. According to these findings, we conclude that regional connections involving fear-processing and re-experiential-processing cortex may play a role in maintaining or adapting to PTSD pathology.
There has been an explosion of interest in mindfulness-based programs (MBPs) such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy. This is demonstrated in increased research, implementation of MBPs in healthcare, educational, criminal justice and workplace settings, and in mainstream interest. For the sustainable development of the field there is a need to articulate a definition of what an MBP is and what it is not. This paper provides a framework to define the essential characteristics of the family of MBPs originating from the parent program MBSR, and the processes which inform adaptations of MBPs for different populations or contexts. The framework addresses the essential characteristics of the program and of teacher. MBPs: are informed by theories and practices that draw from a confluence of contemplative traditions, science, and the major disciplines of medicine, psychology and education; underpinned by a model of human experience which addresses the causes of human distress and the pathways to relieving it; develop a new relationship with experience characterized by present moment focus, decentering and an approach orientation; catalyze the development of qualities such as joy, compassion, wisdom, equanimity and greater attentional, emotional and behavioral self-regulation, and engage participants in a sustained intensive training in mindfulness meditation practice, in an experiential inquiry-based learning process and in exercises to develop understanding. The paper's aim is to support clarity, which will in turn support the systematic development of MBP research, and the integrity of the field during the process of implementation in the mainstream.
Aligning Mental Health Treatments with the Developmental Stage and Needs of Late Adolescents and Young Adults
Transitional age youth (TAY) are in a discrete developmental stage, different from both adolescents and mature adults. Serious mental illness can result in their delayed psychosocial development and morbidity. Systemic, provider, and individual barriers result in poor access to care for these youth, potentially impeding their transition to mature adulthood. Current strategies for TAY treatment include patient centered care, vocational and educational support, and shared decision making. There is a paucity of evidence-based practices to effectively treat this population or provide practice guidelines. The research required to do so should be a priority.
Transitional age foster youth do not typically receive the types of family supports their nonfoster peers enjoy. Many foster youth experience multiple adversities and often fare worse than nonfoster peers on long-term functional outcomes. Governments increasingly recognize their responsibility to act as parents for state dependents transitioning to adulthood and the need to provide services to address social/emotional supports, living skills, finances, housing, education, employment, and physical and mental health. More research is needed to inform the development of effective programs. Transitional age foster youth benefit from policies promoting a developmentally appropriate, comprehensive, and integrated transition system of care.
Research has provided us with a tremendously rich understanding of the perinatal period and the kind of psychotherapeutic techniques that can effectively address issues that arise during this time. It is now time to more fully integrate and disseminate this knowledge to providers who are working with the perinatal population so it can be widely used in thoughtful and nuanced ways.
Yeast one-hybrid (Y1H) assays are used to identify which transcription factor (TF) "preys" can bind a DNA fragment of interest that is used as the "bait." Undertaking Y1H assays requires the generation of a yeast "bait strain" for each DNA fragment of interest that features the DNA bait coupled to a reporter(s). Plasmids encoding TFs fused to the Gal4 activation domain (AD) are then introduced into the bait strain, and activation of the reporter(s) indicates that a TF-DNA interaction has occurred. Here, we present a protocol for the first part of the strategy-the generation of a bait strain for Y1H assays. We assume that the DNA bait has already been cloned into two different reporter constructs: One places the fragment of interest upstream of HIS3, an auxotrophic growth marker, whereas the other places the DNA bait upstream of LacZ, a colorimetric marker that changes colorless X-gal into a blue compound. Briefly, generation of the bait strain involves using homologous recombination to integrate the two reporters into the genome of the yeast strain, screening individual integrants for background reporter expression (i.e., expression in the absence of a TF), and using polymerase chain reaction (PCR) and sequencing to confirm the DNA bait identity from both integrated reporter cassettes.
Yeast one-hybrid (Y1H) assays are used to identify which transcription factor (TF) "prey" molecules can bind a DNA fragment of interest that is used as "bait". Y1H assays involve introducing plasmids that encode TFs into a yeast "bait strain" in which the DNA fragment of interest is integrated upstream of one or more reporters, and activation of these reporters indicates that a TF-DNA interaction has occurred. These plasmids express each TF as a hybrid protein (hence the "one-hybrid" name) fused to the activation domain (AD) of the yeast TF Gal4. The AD moiety activates reporter expression even if the TF to which it is fused typically functions as a repressor. Here, we describe how to perform a Y1H screen of a library of cDNA fragments cloned into a pPC86 plasmid expressing the protein encoded by the cDNA as an AD fusion. The method assumes availability of either commercially available libraries or libraries generated in house using mRNA extracted from a tissue of interest. We also assume that users have access to a yeast bait strain that possesses the DNA fragment of interest integrated upstream of two different reporters-HIS3, an auxotrophic marker, and LacZ, a colorimetric marker that changes colorless X-gal into a blue compound. Briefly, the screen involves transforming the AD-cDNA library into the yeast bait strain, identifying colonies that show activation of both reporters, retesting the interaction in a freshly grown bait strain, and sequencing the cDNA insert to identify the interacting TF.
In this protocol, we present a qualitative assay for monitoring the level of expression of beta-galactosidase, an enzyme encoded by the LacZ gene, in yeast. This is useful both for determining autoactivity of LacZ expression in yeast DNA "bait" strains and for assessing LacZ reporter gene activation mediated by a transcription factor "prey" interaction with a DNA bait of interest in yeast one-hybrid (Y1H) assays. In this colorimetric assay, yeast are lysed in liquid nitrogen and then assayed for beta-galactosidase expression using the colorless compound X-gal, which turns blue in the presence of this enzyme.