Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Psychotherapy Processes Underlying Sudden Gains in Treatment of PTSD

Thesis (Ph.D.)--University of Washington, 2015-12To date, there is a dearth of empirical evidence within the "black box" between pre- and post-treatment to fully understand how and why our interventions work. It is essential to take a process-oriented approach with research to elucidate trajectories and mechanisms of individual change in PTSD treatment. Sudden gains, defined as rapid, large symptom improvements during between-session intervals, have been investigated across different samples and interventions and have consistently been associated with better treatment outcome. Utilizing sudden gains as markers of critical points of transition, the in-session therapist-patient interactions prior to the gains were examined using a process-oriented, detailed coding system for potential processes of change associated with sudden gains. This was the first study to systematically examine in-session therapy content for potential mechanisms triggering sudden gains in PTSD treatment. Pre-treatment trait-like factors of distress tolerance and neuroticism and more proximal factors of fear activation, between-session, and within-session distress reductions were also examined as potential predictors of sudden gains. When examining the pre-gain sessions, patients who experienced sudden gains expressed more positive hope and had more cognitive-emotional processing than those who did not exhibit sudden gains, suggesting these are key elements for discontinuous change. Sudden gains occurred similarly in both PE only and PE combined with sertraline treatment. However, when examining pre-gain in-session content, patients receiving PE only had more cognitive-emotional processing than patients receiving PE combined with sertraline, highlighting potential different mechanisms between the two treatments. Finally, distress tolerance-related absorption predicted the occurrence of sudden gains, suggesting that individuals who pay more attention to negative emotional states and thoughts are more likely to experience a sudden gain. However, no other predictors of neuroticism, fear activation, between-session distress reduction, and within-session distress reduction were associated with sudden gains. All together, the findings of this study bring a better understanding of the sudden gain phenomenon and elucidate what are the key elements of change in PTSD treatment. By enhancing these key elements of change, the efficacy and efficiency of the interventions can be maximized and will allow the tailoring of interventions to specific patients based on his or her needs and strengths of achieving change

Component analysis of a synchronous and asynchronous blended care CBT intervention for symptoms of depression and anxiety: Pragmatic retrospective study.

BackgroundDepression and anxiety are leading causes of disability worldwide. Though effective treatments exist, depression and anxiety remain undertreated. Blended care psychotherapy, combining the scalability of online interventions with the personalization and engagement of a live therapist, is a promising approach for increasing access to evidence-based care.ObjectivesTo evaluate the effectiveness and individual contribution of two components - i) digital tools and ii) video-based therapist-led sessions - in a blended care CBT-based intervention under real world conditions.MethodsA retrospective cohort design was used to analyze N = 1372 US-based individuals who enrolled in blended care psychotherapy. Of these, at baseline, 761 participants had depression symptoms in the clinical range (based on PHQ-9), and 1254 had anxiety symptoms in the clinical range (based on GAD-7). Participants had access to the program as a mental health benefit offered by their employer. The CBT-based blended care psychotherapy program consisted of regular video sessions with therapists, complemented by digital lessons and digital exercises assigned by the clinician and completed in between sessions. Depression and anxiety levels and clients' treatment engagement were tracked throughout treatment. A 3-level individual growth curve model incorporating time-varying covariates was utilized to examine symptom trajectories of PHQ-9 scores (for those with clinical range of depression at baseline) and GAD-7 scores (for those with clinical range of anxiety at baseline).ResultsOn average, individuals exhibited a significant decline in depression and anxiety symptoms during the initial weeks of treatment (P < .001), and a continued decline over subsequent weeks at a slower rate (P < .001). Engaging in a therapy session in a week was associated with lower GAD-7 (b = -0.81) and PHQ-9 (b = -1.01) scores in the same week, as well as lower GAD-7 (b = -0.58) and PHQ-9 (b = -0.58) scores the following week (all P < .01). Similarly, engaging with digital lessons was independently associated with lower GAD-7 (b = -0.19) and PHQ-9 (b = -0.18) scores during the same week, and lower GAD-7 (b = -0.25) and PHQ-9 (b = -0.27) the following week (all P < .01).ConclusionsTherapist-led video sessions and digital lessons had separate contributions to improvements in symptoms of depression and anxiety over the course of treatment. Future research should investigate whether clients' characteristics are related to differential effects of therapist-led and digital components of care

Problematic driving in former service members: An evaluation of the Driving Behavior Survey in veterans with posttraumatic stress disorder

Despite high levels of traffic-related mortality, injury, and impairment among former service members, measures validated to assess problematic driving in this population remain limited. The current study examined characteristics of the Driving Behavior Survey (DBS) in male veterans (76.3% White; age: M = 56.4, SD = 12.3) meeting criteria for PTSD. Confirmatory factor analyses indicated acceptable fit of a 3-factor model specifying dimensions of anxiety-based performance deficits, exaggerated safety/caution, and hostile/aggressive driving behavior. Concurrent associations with indices of anxiety, depression, trauma history, and clinician-rated PTSD were consistent with small (r = .10–.29) to medium (r = .30–.49) effects. Discriminative validity was noted through elevations in performance deficit (d = .26), safety/caution (d = .50), and hostile/aggressive (d = .39) scales relative to published data from student drivers. Scores comparable to civilian motorists with accident-related PTSD help to qualify the severity of problematic driving behavior in trauma-exposed veterans

Pharmacological treatment of anxiety disorders: Current treatments and future directions

Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey three approaches to the development of innovative anxiety treatments: the continued development of drugs based on specific neuroreceptors; the pharmacologigcal manipulation of fear-related memory; and the electrical or electromagnetic stimulation of specific brain areas. We highlight directions for future research, as none of these approaches is ready for clinical use. This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.Medical Research Council (MC_UU_12015/1), Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135), MRC (MC_PC_13048), Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149