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Behavioral determinants with the largest effects are often those related to the environments in which behaviors occur. This suggests the merits of a shift in focus of changing behavior at scale away from interventions based on deliberation and decision-making and toward interventions that involve changing cues – physical, digital, social, and economic – in environments. This chapter focuses on changing cues in small-scale physical environments – sometimes known as choice architecture or nudge interventions. Despite attracting much interest, these interventions have been little explored from a theoretical perspective. Exploring the mechanisms by which some of these interventions exert their effects provides a starting point. Examining evidence of three interventions – increasing availability of healthier food options, reducing glass size, and putting warning labels on food and alcohol products – suggests no single theory explains their effects. The mechanisms by which these interventions affect behavior change also necessitate different levels of explanation and demand a theoretical framework that applies at different levels. Recognizing the distinction between model-free and model-based learning and behavior may be central to this. Advancing knowledge on changing behavior by changing environments requires robustly designed field studies to estimate effect sizes, complemented by laboratory studies testing mechanisms to optimize interventions and develop theoretical understanding.
Large population-based cohort studies of neuropsychological factors that characterise or precede depressive symptoms are rare. Most studies use small case-control or cross-sectional designs, which may cause selection bias and cannot test temporality. In a large UK population-based cohort, we investigated cross-sectional and longitudinal associations between inhibitory control of positive and negative information and adolescent depressive symptoms.
Cohort study of 2328 UK adolescents who completed an affective go/no-go task at age 18. Depressive symptoms were assessed with the Clinical Interview Schedule Revised (CIS-R) and short Mood and Feeling Questionnaire (sMFQ) at age 18, and with the sMFQ 1 year later (age 19). Analyses were multilevel and traditional linear regressions, before and after adjusting for confounders.
Cross-sectionally, we found little evidence that adolescents with more depressive symptoms made more inhibitory control errors [after adjustments, errors increased by 0.04% per 1 s.d. increase in sMFQ score (95% confidence interval 0.02–0.06)], but this association was not observed for the CIS-R. There was no evidence for an influence of valence. Longitudinally, there was no evidence that reduced inhibitory control was associated with future depressive symptoms.
Inhibitory control of positive and negative information does not appear to be a marker of current or future depressive symptoms in adolescents and would not be a useful target in interventions to prevent adolescent depression. Our lack of convincing evidence for associations with depressive symptoms suggests that the affective go/no-go task is not a promising candidate for future neuroimaging studies of adolescent depression.
We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
To evaluate the efficacy of aripiprazole adjunctive antidepressant therapy (ADT) with regard to functioning in patients with major depressive disorder (MDD) who did not achieve an adequate response with standard ADT.
Pooled data were analyzed from three nearly identically designed randomized, double-blind, placebo-controlled trials: CN138-139, CN138-163 and CN138-165. These included patients with MDD, without psychotic features, who had failed at least one ADT treatment in the present episode. Patients completing an 8-week prospective ADT phase with inadequate response were randomized to 6-weeks’ treatment with adjunctive aripiprazole (n=508) or placebo (n=494). Functioning was assessed using the Sheehan Disability Scale (SDS). Comparisons of mean change from baseline in total SDS score, and domains of family life, social life and work/school were performed using ANCOVA.
Adjunctive aripiprazole produced significant improvements in total SDS (-1.2 on an adjusted scale of 1-10, with 10=worst level of functioning/1=best) vs adjunctive placebo (-0.7, p< 0.001). Adjunctive aripiprazole produced significant changes in the family life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001) and the social life domain (-1.4 for adjunctive aripiprazole vs -0.7 for adjunctive placebo, p< 0.001). No difference between groups was observed on the work/school domain (-0.8 for adjunctive aripiprazole and -0.6 for adjunctive placebo, p=0.34).
Adjunctive aripiprazole showed significant improvements in overall SDS scores, and family and social life domains. Less change was observed in the work/school domain. The results emphasize that assessment of patient functioning may have utility both in clinical trials and clinical practice.
To evaluate the long-term safety and efficacy of adjunctive aripiprazole (ARI) to lithium (LI) or valproate (VAL) in delaying time to relapse in bipolar I disorder.
Bipolar I disorder subjects with a current manic or mixed episode received LI or VAL for at least 2 weeks; inadequate responders (YMRS score ≥ 16 and ≤35% decrease from baseline at 2 weeks) received adjunctive ARI. Subjects maintaining mood stability (YMRS and MADRS ≤ 12 for 12 consecutive weeks) were randomised 1:1 to double-blind ARI (10 to 30 mg/day) or placebo (PBO) plus LI or VAL. Relapse was monitored up to 52 weeks.
337 subjects were randomised to continuation of mood stabiliser plus adjunctive ARI or PBO; 61.3% and 52.7%, respectively, completed the study. Adjunctive ARI significantly delayed the time to any relapse, hazard ratio = 0.544 (95% CI: 0.33, 0.89, log-rank p = 0.014). Overall relapse rates at 52 weeks were 14.9% and 25.4% in ARI vs PBO subjects. A superior reduction in CGI-BP Mania Severity of Illness from baseline at 52 weeks was also observed (0.3 vs. 0.0, respectively, p = 0.01). Adverse events generally were as expected per known drug and illness profiles with no significant difference in mean change in body weight between adjunctive PBO (0.60 kg) and adjunctive ARI (1.07 kg) (p = 0.49 Week 52, LOCF).
Continuation of aripiprazole treatment increased time to relapse to any mood episode compared with placebo plus LI/VAL over 1 year, indicating a long-term benefit in continuing adjunctive aripiprazole to a mood stabiliser after sustained remission is achieved.
There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene–environment correlation.
The association between schizophrenia polygenic scores (PGS) and experiencing childhood trauma was investigated using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother, Father and Child Cohort Study (MoBa). Schizophrenia PGS were derived in each cohort for children, mothers, and fathers where genetic data were available. Measures of trauma exposure were derived based on data collected throughout childhood and adolescence (0–17 years; ALSPAC) and at age 8 years (MoBa).
Within ALSPAC, we found a positive association between schizophrenia PGS and exposure to trauma across childhood and adolescence; effect sizes were consistent for both child or maternal PGS. We found evidence of an association between the schizophrenia PGS and the majority of trauma subtypes investigated, with the exception of bullying. These results were comparable with those of MoBa. Within ALSPAC, genetic liability to a range of additional psychiatric traits was also associated with a greater trauma exposure.
Results from two international birth cohorts indicate that genetic liability for a range of psychiatric traits is associated with experiencing childhood trauma. Genome-wide association study of psychiatric phenotypes may also reflect risk factors for these phenotypes. Our findings also suggest that youth at higher genetic risk might require greater resources/support to ensure they grow-up in a healthy environment.
Hepatitis B vaccination is recommended for men who have sex with men (MSM) in many countries, but information on vaccine coverage is scarce. We studied hepatitis B vaccination programmes and coverage among MSM in Europe to guide prevention. From a large (N = 174 209) pan-European MSM survey (EMIS-2010), we used data on self-reported hepatitis B vaccination, age, education, settlement size and disclosure of the same-sex sexual orientation (‘outness’). We excluded participants with a history of hepatitis B. In multilevel (participants, countries) logistic regression models, we calculated adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). We analysed data of 163 987 MSM in 38 European countries: 38.3% were ‘out’ to all or almost all, 56.4% reported vaccination against hepatitis B and 65.5% lived in countries with free recommended hepatitis B vaccination for MSM. In the final model the odds for being vaccinated increased with outness (‘out to all or almost all’: aOR 1.76, 95% CI 1.70–1.83 vs. ‘out to no one’) and with living in countries, where hepatitis B vaccination was recommended and free-of-charge for MSM (aOR 2.21, 95% CI 1.47–3.32 vs. ‘no or unclear recommendation’). To increase hepatitis B vaccination coverage among MSM, implementation of MSM-specific recommendations and improvement of the societal climate for MSM is needed.
It is unclear what session frequency is most effective in cognitive–behavioural therapy (CBT) and interpersonal psychotherapy (IPT) for depression.
Compare the effects of once weekly and twice weekly sessions of CBT and IPT for depression.
We conducted a multicentre randomised trial from November 2014 through December 2017. We recruited 200 adults with depression across nine specialised mental health centres in the Netherlands. This study used a 2 × 2 factorial design, randomising patients to once or twice weekly sessions of CBT or IPT over 16–24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II at baseline, before session 1, and 2 weeks, 1, 2, 3, 4, 5 and 6 months after start of the intervention. Intention-to-treat analyses were conducted.
Compared with patients who received weekly sessions, patients who received twice weekly sessions showed a statistically significant decrease in depressive symptoms (estimated mean difference between weekly and twice weekly sessions at month 6: 3.85 points, difference in effect size d = 0.55), lower attrition rates (n = 16 compared with n = 32) and an increased rate of response (hazard ratio 1.48, 95% CI 1.00–2.18).
In clinical practice settings, delivery of twice weekly sessions of CBT and IPT for depression is a way to improve depression treatment outcomes.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to evaluate specific aspects of instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 660c, the fourth generation of this powder diffraction SRM, which is used primarily for calibrating powder diffractometers with respect to line position and line shape for the determination of the instrument profile function (IPF). It is certified with respect to lattice parameter and consists of approximately 6 g of lanthanum hexaboride (LaB6) powder. So that this SRM would be applicable for the neutron diffraction community, the powder was prepared from an isotopically enriched 11B precursor material. The microstructure of the LaB6 powder was engineered specifically to yield a crystallite size above that where size broadening is typically observed and to minimize the crystallographic defects that lead to strain broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the LaB6 powder. Both Type A, statistical, and Type B, systematic, uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.415 682 6 ± 0.000 008 nm (95% confidence).
Healthy diet has been linked to better age-related functioning, but evidence on the relationship of diet quality in late midlife and measures of physical capability in later life is limited. Research on potential sex differences in this relationship is scarce. The aim was to investigate the prospective association between overall diet quality, as assessed by the Healthy Eating Index-2015 (HEI-2015) at 60–64 years and measures of walking speed 7 years later, among men and women from the Insight 46, a neuroscience sub-study of the Medical Research Council National Survey of Health and Development. Diet was assessed at 60–64 years using 5-d food diaries, from which total HEI-2015 was calculated. At 69–71 years, walking speed was estimated during four 10-m walks at self-selected pace, using inertial measurement units. Multivariable linear regression models with sex as a modifier, controlling for age, follow-up, lifestyle, health/social variables and physical performance, were used. The final sample consists of 164 women and 167 men (n 331). Women had higher HEI-2015 and slower walking speed than men. A 10-point increase in HEI-2015 was associated with faster walking speed among women (B 0·024, 95 % CI 0·006, 0·043), but not men. The association remained significant in the multivariable model (B 0·021, 95 % CI 0·003, 0·040). In women, higher diet quality in late midlife is associated with faster walking speed. A healthy diet in late midlife is likely to contribute towards better age-related physical capability, and sex differences are likely to affect this relationship.
Psychotherapies for depression are equally effective on average, but individual responses vary widely. Outcomes can be improved by optimizing treatment selection using multivariate prediction models. A promising approach is the Personalized Advantage Index (PAI) that predicts the optimal treatment for a given individual and the magnitude of the advantage. The current study aimed to extend the PAI to long-term depression outcomes after acute-phase psychotherapy.
Data come from a randomized trial comparing cognitive therapy (CT, n = 76) and interpersonal psychotherapy (IPT, n = 75) for major depressive disorder (MDD). Primary outcome was depression severity, as assessed by the BDI-II, during 17-month follow-up. First, predictors and moderators were selected from 38 pre-treatment variables using a two-step machine learning approach. Second, predictors and moderators were combined into a final model, from which PAI predictions were computed with cross-validation. Long-term PAI predictions were then compared to actual follow-up outcomes and post-treatment PAI predictions.
One predictor (parental alcohol abuse) and two moderators (recent life events; childhood maltreatment) were identified. Individuals assigned to their PAI-indicated treatment had lower follow-up depression severity compared to those assigned to their PAI-non-indicated treatment. This difference was significant in two subsets of the overall sample: those whose PAI score was in the upper 60%, and those whose PAI indicated CT, irrespective of magnitude. Long-term predictions did not overlap substantially with predictions for acute benefit.
If replicated, long-term PAI predictions could enhance precision medicine by selecting the optimal treatment for a given depressed individual over the long term.
Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
In contrast to arbitrariness, a recent perspective is that words contain both arbitrary and iconic aspects. We investigated iconicity in word recognition, and the possibility that iconic words have special links between phonological and semantic features that may facilitate their processing. In Experiment 1, participants completed a lexical decision task (“Is this letter string a word?”) including words varying in their iconicity. Notably, we manipulated stimulus presentation conditions such that the items were visually degraded for half of the participants; this manipulation has been shown to increase reliance on phonology. Responses to words higher in iconicity were faster and more accurate, but this did not interact with condition. In Experiment 2 we explicitly directed participants’ attention to phonology by using a phonological lexical decision task (“Does this letter string sound like a word?”). Responses to words that were higher in iconicity were once again faster. These results demonstrate facilitatory effects of iconicity in lexical processing, thus showing that the benefits of iconic mappings extend beyond those reported for language learning and those argued for language evolution.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.
We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.
We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.
Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).
These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.
Declaration of interest
W.v.d.B received fees in the past 3 years from Indivior, C&A Pharma, Opiant and Angelini. G.M.G. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator, holds shares in P1vital and has served as consultant, advisor or CME speaker in the past 3 years for Allergan, Angelini, Compass Pathways, MSD, Lundbeck (/Otsuka and /Takeda), Medscape, Minervra, P1Vital, Pfizer, Sage, Servier, Shire and Sun Pharma.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Buddhist and Hindu discourse often juxtapose statements about the inexpressibility of ultimate reality with descriptions drawing on metaphor and paradox. This raises the question of how particular types of metaphor fulfill the role of expressing what is believed to be inexpressible. The current study employs a cognitive linguistic framework to examine how modern Buddhist and Hindu religious teachers use metaphor to talk about enlightenment. Adopting a usage-based approach focusing on how figurative language is recontexualized by the same speaker within a stretch of discourse, the study identifies a recurrent pattern within the discourse on enlightenment that consists of four elements. The first is source domain reversal, which we define as a speaker making use of a particular source domain to refer to a target, and then later, in the same discourse segment, using a source domain with a seemingly opposite meaning to refer to the same target. The other three involve a movement from force to object-based schemas, from the perceived revelation of more conventional to deeper truths, and from description of a process to description of a state. We conclude by briefly discussing our findings within the context of research on apophatic discourse in other religions.