To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
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.
The National Institute of Standards and Technology (NIST) certifies a suite of Standard Reference Materials (SRMs) to be used to evaluate specific aspects of the instrument performance of both X-ray and neutron powder diffractometers. This report describes SRM 640f, the seventh generation of this powder diffraction SRM, which is designed to be used primarily for calibrating powder diffractometers with respect to line position; it also can be used for the determination of the instrument profile function. It is certified with respect to the lattice parameter and consists of approximately 7.5 g of silicon powder prepared to minimize line broadening. A NIST-built diffractometer, incorporating many advanced design features, was used to certify the lattice parameter of the Si powder. Both statistical and systematic uncertainties have been assigned to yield a certified value for the lattice parameter at 22.5 °C of a = 0.5431144 ± 0.000008 nm.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
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 long-term tolerability and effectiveness of aripiprazole adjunctive to lithium or valproate in bipolar mania.
Completers of a 6-week double-blind comparison of adjunctive aripiprazole versus placebo in bipolar mania partially responsive to monotherapy were followed up over 46-weeks on open-label aripiprazole plus lithium (ARI+LI) or valproate (ARI+VAL).
283 (ARI+LI n=108; ARI+VAL n=175) patients entered and 146 (ARI+LI n=55; ARI+VAL n=91) completed the 46-week extension. Safety results for both combinations were consistent with the known tolerability profile of aripiprazole, lithium and valproate. No clinically significant changes in lipids or glucose were observed with either ARI+LI or ARI+VAL. Mean (SE) weight change from double-blind endpoint to Week 46 (LOCF) was 2.3 (0.6) kg with ARI+LI and 2.0 (0.4) kg with ARI+VAL. Temporal analysis of the time of first onset of adverse events showed that akathisia and insomnia tended to occur early in treatment, with few new cases in patients previously treated with aripiprazole during the 6-week study.
Significant improvements from baseline in YMRS total score and MADRS total score were sustained over the 52 weeks with both ARI+LI and ARI+VAL treatment.
Mean reduction from baseline at Week 52 LOCF[95%CI], p value vs baseline
YMRS total score
-16.5 [-18.1; -14.8], p<0.001
-17.6 [-18.9; -16.3] p<0.001
MADRS total score
-1.7 [-3.3; -0.1] p<0.05
-2.7 [-4.0; -1.4] p<0.001
Long-term aripiprazole adjunctive to lithium/valproate in bipolar mania was safe and well-tolerated. Improvements in manic and depressive symptoms observed during the first 6 weeks of treatment were maintained.
To evaluate the efficacy of aripiprazole as adjunctive treatment in patients with major depressive disorder (MDD) without psychotic features and an inadequate response to standard antidepressant therapy (ADT).
Data were collected from three identical, short-term, double-blind, placebo-controlled studies (CN138-139, CN138-163, CN138-165). After a single-blind prospective phase with placebo plus ADT, patients with inadequate response were randomized to 6-weeks’ treatment with adjunctive aripiprazole or placebo. The primary efficacy endpoint was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) total score during the double-blind phase. Secondary endpoints were response (≥50% reduction in MADRS total score), remission (MADRS total score ≤10 and ≥50% reduction in MADRS total score), and mean change in Hamilton Depression Rating Scale (HAM-D17) total score.
In all three studies, adjunctive aripiprazole was associated with a significantly greater reduction in MADRS total score than adjunctive placebo, with a treatment difference ranging between -3.73 and -2.84 (p≤0.001 in each study). Response and remission rates with adjunctive aripiprazole (32.4-46.6% and 25.4-36.8%, respectively) were also significantly higher than with adjunctive placebo (17.4-26.6% [p< 0.05 in each study] and 15.2-18.9% [p< 0.05 in each study]). Mean change in HAM-D17 total score ranged from -7.64 to -6.77 with adjunctive aripiprazole and from -5.12 to -4.41 with adjunctive placebo (p< 0.001 for each study).
Results of the three studies indicate that treatment with adjunctive aripiprazole and ADT is effective in improving the symptoms of MDD in patients who have had an inadequate response to ADT.
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 efficacy and safety of aripiprazole monotherapy as acute and continuation therapy for acute bipolar I mania.
Patients with acute bipolar I mania were randomized (1:1:1) to double-blind aripiprazole (15–30 mg/day; n=155), placebo (n=165) or lithium (900–1500 mg/day; n=160) for 3 weeks. At the end of Week 3, patients randomized to placebo were blindly switched to aripiprazole. Key efficacy outcome measures were mean change from baseline in YMRS Total score at Week 3 (LOCF; primary endpoint) and Week 12.
Improvements in YMRS Total scores from baseline were significantly greater versus placebo as early as Day 2 with aripiprazole (p=0.003) and Day 7 with lithium (p=0.040; LOCF). At Week 3, improvements from baseline in mean YMRS Total scores were significantly greater with aripiprazole (–12.96; p<0.001) and lithium (–12.03; p=0.005) versus placebo (–9.01; LOCF). These improvements were maintained to Week 12 (LOCF) with both aripiprazole (–14.48) and lithium (–12.71). Response rate was significantly greater versus placebo as early as Day 2 with aripiprazole (p=0.026), and Day 10 with lithium (p=0.006; LOCF). Response rates continued to increase over the study period and at Week 12 were 56.5% with aripiprazole and 49.0% with lithium.
Aripiprazole significantly improved symptoms as early as Day 2 and throughout the 3-week, placebo-controlled portion of this study in acutely manic patients. The beneficial effects of aripiprazole were sustained through Week 12 and were similar to lithium, confirming the robust efficacy of aripiprazole in these patients.
Evaluate the time-course, severity and resolution patterns of adverse events (AEs) occurring with long-term aripiprazole treatment for irritability associated with autistic disorder.
Participants were treated with aripiprazole in a 52-week, open-label, flexibly dosed (2–15 mg/day) study. Subjects had either completed one of two 8-week randomised trials or were de novo. AEs with an incidence of ≥10% were evaluated by incidence, peak first onset, severity, percent resolved and time to resolution.
A total of 330 subjects entered open-label treatment; 199 completed 52 weeks. Mean dose for the population stabilised at around 10 mg/day after approximately 4 months. Thirteen AEs had an incidence of ≥10%; most were mild or moderate in severity. Vomiting, diarrhoea and headache had an early first onset and tended to resolve fairly quickly.
Sedation, fatigue and insomnia also appeared early and resolved in a majority of cases, but not as quickly. Increased appetite appeared early (followed by increased weight) and fewer weight-related AEs resolved. More than half of the subjects increased their weight by at least one percentile category rank; nevertheless, only a small proportion of subjects with normal baseline metabolic or glucose measures had a treatment-emergent, clinically relevant laboratory abnormality. Nasopharyngitis, upper respiratory infection, cough, nasal congestion and pyrexia all had peak onset at variable times during the study, resolving in nearly all cases, with short time to resolution.
AEs were mostly mild or moderate and of variable duration. Increased weight was observed.
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.
To evaluate the efficacy, safety and tolerability of aripiprazole plus valproate/lithium in the treatment of patients with bipolar I mania partially non-responsive to lithium or valproate monotherapy.
This multicentre, randomized study included patients with bipolar I disorder (manic/mixed episode, with/without psychotic features). Partial non-responders with therapeutic lithium (0.6–1.0 mmol/l) or valproate (50–125 μg/ml) levels were randomized (2:1) to double-blind combination aripiprazole (aripiprazole [15–30 mg/day] + lithium/valproate; n=253) or placebo + lithium/valproate (n=131). The primary endpoint was mean change from baseline in YMRS Total Score at Week 6 (LOCF).
The aripiprazole combination therapy demonstrated significant improvement from baseline in the YMRS Total score versus placebo + lithium/valproate at Week 1 and all subsequent visits (all p<0.05) up to Week 6 (–13.3 vs. –10.7, p=0.002; LOCF). Significant improvements from baseline to Week 6 were observed with aripiprazole vs. placebo + lithium/valproate in CGI-BP-S (mania) score (–1.9 vs. –1.6; p=0.014; LOCF) and the LIFE-RIFT score (–1.76 vs. –0.99; p=0.046; LOCF). At endpoint, aripiprazole plus lithium/valproate was associated with significantly greater remission rate (YMRS Total score ≤12) and response rate (≥50% improvement from baseline in YMRS Total) than placebo + lithium/valproate. Similar percentages of patients had clinically relevant weight gain (aripiprazole + lithium/valproate vs. placebo + lithium/valproate: 3.0% vs. 3.9%; p=0.718, Week 6, LOCF). Aripiprazole combination therapy was well tolerated.
In patients with bipolar mania, aripiprazole in combination with lithium/valproate is an effective and well-tolerated treatment that improves psychosocial functioning.
Previous literature has demonstrated a strong association between cigarette smoking, suicidal ideation and suicide attempts. This association has not previously been examined in a causal inference framework and could have important implications for suicide prevention strategies.
We aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation analyses.
First, in the UK Biobank, we calculated observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation to explore the relationship between smoking and suicide attempts and ideation, using genetic variants as instruments to reduce bias from residual confounding and reverse causation.
Our observational analysis showed a relationship between smoking behaviour, suicidal ideation and attempts, particularly between smoking initiation and suicide attempts (odds ratio, 2.07; 95% CI 1.91–2.26; P < 0.001). The Mendelian randomisation analysis and single-nucleotide polymorphism analysis, however, did not support this (odds ratio for lifetime smoking on suicidal ideation, 0.050; 95% CI −0.027 to 0.127; odds ratio on suicide attempts, 0.053; 95% CI, −0.003 to 0.110). Despite past literature showing a positive dose-response relationship, our results showed no clear evidence for a causal effect of smoking on suicidal ideation or attempts.
This was the first Mendelian randomisation study to explore the effect of smoking on suicidal ideation and attempts. Our results suggest that, despite observed associations, there is no clear evidence for a causal effect.
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.
There is demand for new, effective and scalable treatments for depression, and development of new forms of cognitive bias modification (CBM) of negative emotional processing biases has been suggested as possible interventions to meet this need.
We report two double blind RCTs, in which volunteers with high levels of depressive symptoms (Beck Depression Inventory ii (BDI-ii) > 14) completed a brief course of emotion recognition training (a novel form of CBM using faces) or sham training. In Study 1 (N = 36), participants completed a post-training emotion recognition task whilst undergoing functional magnetic resonance imaging to investigate neural correlates of CBM. In Study 2 (N = 190), measures of mood were assessed post-training, and at 2-week and 6-week follow-up.
In both studies, CBM resulted in an initial change in emotion recognition bias, which (in Study 2) persisted for 6 weeks after the end of training. In Study 1, CBM resulted in increases neural activation to happy faces, with this effect driven by an increase in neural activity in the medial prefrontal cortex and bilateral amygdala. In Study 2, CBM did not lead to a reduction in depressive symptoms on the BDI-ii, or on related measures of mood, motivation and persistence, or depressive interpretation bias at either 2 or 6-week follow-ups.
CBM of emotion recognition has effects on neural activity that are similar in some respects to those induced by Selective Serotonin Reuptake Inhibitors (SSRI) administration (Study 1), but we find no evidence that this had any later effect on self-reported mood in an analogue sample of non-clinical volunteers with low mood (Study 2).
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).
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.
Identification of individuals with clinically significant aggressive behavior is critical for the prevention and management of human aggressive behavior. A previous population-based taxometric study reported that the Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) intermittent explosive disorder (IED) belongs to its own discrete class (taxon) rather than existing along a continuum.
This study sought to extend previous population-based findings in a clinical research sample of adults with DSM-5 IED (n = 346), adults with non-aggressive DSM-5 disorders (n = 293), and adults without any DSM-5 disorder (n = 174), using standardized assessments of DSM-5 diagnoses, aggression, and other related measures not available in past studies.
Analyses revealed a taxonic latent structure that overlapped with the DSM-5 diagnosis of IED. Within the sample, taxon group members had higher scores on a variety of measures of psychopathology than did the complement members of the sample. Comorbidity of other diagnoses with IED did not affect these results.
These findings support the proposition that DSM-5 IED represents a distinct behavioral disorder rather than the severe end of an aggressive behavior continuum.