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Differential susceptibility theory (DST) posits that individuals differ in their developmental plasticity: some children are highly responsive to both environmental adversity and support, while others are less affected. According to this theory, “plasticity” genes that confer risk for psychopathology in adverse environments may promote superior functioning in supportive environments. We tested DST using a broad measure of child genetic liability (based on birth parent psychopathology), adoptive home environmental variables (e.g., marital warmth, parenting stress, and internalizing symptoms), and measures of child externalizing problems (n = 337) and social competence (n = 330) in 54-month-old adopted children from the Early Growth and Development Study. This adoption design is useful for examining DST because children are placed at birth or shortly thereafter with nongenetically related adoptive parents, naturally disentangling heritable and postnatal environmental effects. We conducted a series of multivariable regression analyses that included Gene × Environment interaction terms and found little evidence of DST; rather, interactions varied depending on the environmental factor of interest, in both significance and shape. Our mixed findings suggest further investigation of DST is warranted before tailoring screening and intervention recommendations to children based on their genetic liability or “sensitivity.”
Children with autism spectrum disorder (ASD) have increased susceptibility to anxiety disorders. Variation in a common ASD symptom, insistence on sameness behaviour, may predict future anxiety symptoms.
To describe the joint heterogeneous longitudinal trajectories of insistence on sameness and anxiety in children with ASD and to characterise subgroups at higher risk for anxiety.
In a longitudinal ASD cohort (n = 421), insistence on sameness behaviour was measured using the Autism Diagnostic Interview-Revised at approximately ages 3, 6 and 11 years. Anxiety was quantified at 8 time points between ages 3 and 11 years using the Child Behavior Checklist (CBCL) (parent report). Clusters of participants following similar trajectories were identified using group-based and joint trajectory modelling.
Three insistence on sameness trajectories were identified: (a) ‘low-stable’ (41.7% of participants), (b) ‘moderate-increasing’ (52.0%) and (c) ‘high-peaking’ (i.e. increasing then stabilising/decreasing behaviour) (6.3%). Four anxiety trajectories were identified: (a) ‘low-increasing’ (51.0%), (b) ‘moderate-decreasing’ (16.2%), (c) ‘moderate-increasing’ (19.6%) and (d) ‘high-stable’ (13.1%). Of those assigned to the ‘high-peaking’ insistence on sameness trajectory, 95% jointly followed an anxiety trajectory that surpassed the threshold for clinical concern (T-score >65) by middle childhood (anxiety trajectories 3 or 4). Insistence on sameness and anxiety trajectories were similar in severity and direction for 64% of the sample; for 36%, incongruous patterns were seen (e.g. decreasing anxiety and increasing insistence on sameness).
The concurrent assessment of insistence on sameness behaviour and anxiety in ASD may help in understanding current symptom profiles and anticipating future trajectories. High preschool insistence on sameness in particular may be associated with elevated current or future anxiety symptoms.
Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.
Commercialization of 2,4-D–tolerant crops is a major concern for sweetpotato producers because of potential 2,4-D drift that can cause severe crop injury and yield reduction. A field study was initiated in 2014 and repeated in 2015 to assess impacts of reduced rates of 2,4-D, glyphosate, or a combination of 2,4-D with glyphosate on sweetpotato. In one study, 2,4-D and glyphosate were applied alone and in combination at 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of anticipated field use rates (1.05 kg ha−1 for 2,4-D and 1.12 kg ha−1 for glyphosate) to ‘Beauregard’ sweetpotato at storage root formation (10 days after transplanting [DAP]). In a separate study, all these treatments were applied to ‘Beauregard’ sweetpotato at storage root development (30 DAP). Injury with 2,4-D alone or in combination with glyphosate was generally equal or greater than with glyphosate applied alone at equivalent herbicide rates, indicating that injury is attributable mostly to 2,4-D in the combination. There was a quadratic increase in crop injury and quadratic decrease in crop yield (with respect to most yield grades) with increased rate of 2,4-D applied alone or in combination with glyphosate applied at storage root development. However, neither the results of this relationship nor of the significance of herbicide rate were observed on crop injury or sweetpotato yield when herbicide application occurred at storage root formation, with a few exceptions. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of 2,4-D applied alone or in combination with glyphosate, although injury observed at lower rates was also a concern after initial observation by sweetpotato producers. However, in some cases, yield reduction of U.S. no.1 and marketable grades was also observed after application of 1/250×, 1/100×, or 1/10× rates of 2,4-D alone or with glyphosate when applied at storage root development.
A major concern of sweetpotato producers is the potential negative effects from herbicide drift or sprayer contamination events when dicamba is applied to nearby dicamba-resistant crops. A field study was initiated in 2014 and repeated in 2015 to assess the effects of reduced rates of N,N-Bis-(3-aminopropyl)methylamine (BAPMA) or diglycloamine (DGA) salt of dicamba, glyphosate, or a combination of these individually in separate trials with glyphosate on sweetpotato. Reduced rates of 1/10, 1/100, 1/250, 1/500, 1/750, and 1/1,000 of the 1× use rate of each dicamba formulation at 0.56 kg ha−1, glyphosate at 1.12 kg ha−1, and a combination of the two at aforementioned rates were applied to ‘Beauregard’ sweetpotato at storage root formation (10 d after transplanting) in one trial and storage root development (30 d after transplanting) in a separate trial. Injury with each salt of dicamba (BAPMA or DGA) applied alone or with glyphosate was generally equal to or greater than glyphosate applied alone at equivalent rates, indicating that injury is most attributable to the dicamba in the combination. There was a quadratic increase in crop injury and a quadratic decrease in crop yield (with respect to most yield grades) observed with an increased herbicide rate of dicamba applied alone or in combination with glyphosate applied at storage root development. However, with a few exceptions, neither this relationship nor the significance of herbicide rate was observed on crop injury or sweetpotato yield when herbicide application occurred at the storage root formation stage. In general, crop injury and yield reduction were greatest at the highest rate (1/10×) of either salt of dicamba applied alone or in combination with glyphosate, although injury observed at lower rates would be cause for concern after initial observation by sweetpotato producers. However, in some cases yield reduction of No.1 and marketable grades was observed following 1/250×, 1/100×, or 1/10× application rates of dicamba alone or with glyphosate when applied at storage root development.
Convolutional neural networks are a subclass of deep learning or artificial intelligence that are predominantly used for image analysis and classification. This proof-of-concept study attempts to train a convolutional neural network algorithm that can reliably determine if the middle turbinate is pneumatised (concha bullosa) on coronal sinus computed tomography images.
Consecutive high-resolution computed tomography scans of the paranasal sinuses were retrospectively collected between January 2016 and December 2018 at a tertiary rhinology hospital in Australia. The classification layer of Inception-V3 was retrained in Python using a transfer learning method to interpret the computed tomography images. Segmentation analysis was also performed in an attempt to increase diagnostic accuracy.
The trained convolutional neural network was found to have diagnostic accuracy of 81 per cent (95 per cent confidence interval: 73.0–89.0 per cent) with an area under the curve of 0.93.
A trained convolutional neural network algorithm appears to successfully identify pneumatisation of the middle turbinate with high accuracy. Further studies can be pursued to test its ability in other clinically important anatomical variants in otolaryngology and rhinology.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Aging is associated with numerous stressors that negatively impact older adults’ well-being. Resilience improves ability to cope with stressors and can be enhanced in older adults. Senior housing communities are promising settings to deliver positive psychiatry interventions due to rising resident populations and potential impact of delivering interventions directly in the community. However, few intervention studies have been conducted in these communities. We present a pragmatic stepped-wedge trial of a novel psychological group intervention intended to improve resilience among older adults in senior housing communities.
A pragmatic modified stepped-wedge trial design.
Five senior housing communities in three states in the US.
Eighty-nine adults over age 60 years residing in independent living sector of senior housing communities.
Raise Your Resilience, a manualized 1-month group intervention that incorporated savoring, gratitude, and engagement in value-based activities, administered by unlicensed residential staff trained by researchers. There was a 1-month control period and a 3-month post-intervention follow-up.
Validated self-report measures of resilience, perceived stress, well-being, and wisdom collected at months 0 (baseline), 1 (pre-intervention), 2 (post-intervention), and 5 (follow-up).
Treatment adherence and satisfaction were high. Compared to the control period, perceived stress and wisdom improved from pre-intervention to post-intervention, while resilience improved from pre-intervention to follow-up. Effect sizes were small in this sample, which had relatively high baseline resilience. Physical and mental well-being did not improve significantly, and no significant moderators of change in resilience were identified.
This study demonstrates feasibility of conducting pragmatic intervention trials in senior housing communities. The intervention resulted in significant improvement in several measures despite ceiling effects. The study included several features that suggest high potential for its implementation and dissemination across similar communities nationally. Future studies are warranted, particularly in samples with lower baseline resilience or in assisted living facilities.
Cultures around the world are converging as populations become more connected. On the one hand this increased connectedness can promote the recombination of existing cultural practices to generate new ones, but on the other it may lead to the replacement of traditional practices and global WEIRDing. Here we examine the process and causes of changes in cultural traits concerning wild plant knowledge in Mbendjele BaYaka hunter–gatherers from Congo. Our results show that the BaYaka who were born in town reported knowing and using fewer plants than the BaYaka who were born in forest camps. Plant uses lost in the town-born BaYaka related to medicine. Unlike the forest-born participants, the town-born BaYaka preferred Western medicine over traditional practices, suggesting that the observed decline of plant knowledge and use is the result of replacement of cultural practices with the new products of cumulative culture.
Depression and chronic inflammatory medical conditions have been linked to impaired cognitive ability. However despite frequent comorbidity, their combined association with cognitive ability has rarely been examined.
This study examined associations between self-reported depression and chronic inflammatory diseases and their interaction with cognitive performance in 456,748 participants of the UK Biobank, adjusting for sociodemographic and lifestyle factors. Numbers with available data ranged from 94,899 to 453,208 depending on the cognitive test.
Self-reported depression was associated with poorer performance compared to controls in several cognitive tests (fully adjusted models, reaction time: B = 6.08, 95% CI = 5.09, 7.07; pairs matching: incidence rate ratio = 1.02, 95% CI = 1.02, 1.03; Trail Making Test B: B = 1.37, 95% CI = 0.88, 1.87; Digit Symbol Substitution Test (DSST): B = −0.35, 95% CI = −0.44, −0.27). Self-reported chronic inflammatory conditions were associated with slower reaction time (B = 3.79, 95% CI = 2.81, 4.78) and lower DSST scores (B = −0.21, 95% CI = −0.30, −0.13). No interaction effects were observed.
In this large, population-based study we provide evidence of lower cognitive performance in both depression and a comprehensive category of chronic inflammatory conditions. Results are consistent with additive effects of both types of disorder on cognitive ability. Clinicians should be aware of such effects, particularly as cognitive impairment is linked to poorer disease outcomes and quality of life.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Major depressive disorder and neuroticism (Neu) share a large genetic basis. We sought to determine whether this shared basis could be decomposed to identify genetic factors that are specific to depression.
We analysed summary statistics from genome-wide association studies (GWAS) of depression (from the Psychiatric Genomics Consortium, 23andMe and UK Biobank) and compared them with GWAS of Neu (from UK Biobank). First, we used a pairwise GWAS analysis to classify variants as associated with only depression, with only Neu or with both. Second, we estimated partial genetic correlations to test whether the depression's genetic link with other phenotypes was explained by shared overlap with Neu.
We found evidence that most genomic regions (25/37) associated with depression are likely to be shared with Neu. The overlapping common genetic variance of depression and Neu was genetically correlated primarily with psychiatric disorders. We found that the genetic contributions to depression, that were not shared with Neu, were positively correlated with metabolic phenotypes and cardiovascular disease, and negatively correlated with the personality trait conscientiousness. After removing shared genetic overlap with Neu, depression still had a specific association with schizophrenia, bipolar disorder, coronary artery disease and age of first birth. Independent of depression, Neu had specific genetic correlates in ulcerative colitis, pubertal growth, anorexia and education.
Our findings demonstrate that, while genetic risk factors for depression are largely shared with Neu, there are also non-Neu-related features of depression that may be useful for further patient or phenotypic stratification.
Cognitive impairment is strongly linked with persistent disability in people with mood disorders, but the factors that explain cognitive impairment in this population are unclear.
To estimate the total effect of (a) bipolar disorder and (b) major depression on cognitive function, and the magnitude of the effect that is explained by potentially modifiable intermediate factors.
Cross-sectional study using baseline data from the UK Biobank cohort. Participants were categorised as having bipolar disorder (n = 2709), major depression (n = 50 975) or no mood disorder (n = 102 931 and n = 105 284). The outcomes were computerised tests of reasoning, reaction time and memory. The potential mediators were cardiometabolic disease and psychotropic medication. Analyses were informed by graphical methods and controlled for confounding using regression, propensity score-based methods and G-computation.
Group differences of small magnitude were found on a visuospatial memory test. Z-score differences for the bipolar disorder group were in the range −0.23 to −0.17 (95% CI −0.39 to −0.03) across different estimation methods, and for the major depression group they were approximately −0.07 (95% CI −0.10 to −0.03). One-quarter of the effect was mediated via psychotropic medication in the bipolar disorder group (−0.05; 95% CI −0.09 to −0.01). No evidence was found for mediation via cardiometabolic disease.
In a large community-based sample in middle to early old age, bipolar disorder and depression were associated with lower visuospatial memory performance, in part potentially due to psychotropic medication use. Mood disorders and their treatments will have increasing importance for population cognitive health as the proportion of older adults continues to grow.
Declaration of interest
I.J.D. is a UK Biobank participant. J.P.P. is a member of the UK Biobank Steering Committee.
Review findings on the role of dietary patterns in preventing depression are inconsistent, possibly due to variation in assessment of dietary exposure and depression. We studied the association between dietary patterns and depressive symptoms in six population-based cohorts and meta-analysed the findings using a standardised approach that defined dietary exposure, depression assessment and covariates.
Included were cross-sectional data from 23 026 participants in six cohorts: InCHIANTI (Italy), LASA, NESDA, HELIUS (the Netherlands), ALSWH (Australia) and Whitehall II (UK). Analysis of incidence was based on three cohorts with repeated measures of depressive symptoms at 5–6 years of follow-up in 10 721 participants: Whitehall II, InCHIANTI, ALSWH. Three a priori dietary patterns, Mediterranean diet score (MDS), Alternative Healthy Eating Index (AHEI-2010), and the Dietary Approaches to Stop Hypertension (DASH) diet were investigated in relation to depressive symptoms. Analyses at the cohort-level adjusted for a fixed set of confounders, meta-analysis used a random-effects model.
Cross-sectional and prospective analyses showed statistically significant inverse associations of the three dietary patterns with depressive symptoms (continuous and dichotomous). In cross-sectional analysis, the association of diet with depressive symptoms using a cut-off yielded an adjusted OR of 0.87 (95% confidence interval 0.84–0.91) for MDS, 0.93 (0.88–0.98) for AHEI-2010, and 0.94 (0.87–1.01) for DASH. Similar associations were observed prospectively: 0.88 (0.80–0.96) for MDS; 0.95 (0.84–1.06) for AHEI-2010; 0.90 (0.84–0.97) for DASH.
Population-scale observational evidence indicates that adults following a healthy dietary pattern have fewer depressive symptoms and lower risk of developing depressive symptoms.
The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
The concept of electoral competition plays a central role in many subfields of political science, but no consensus exists on how to measure it. One key challenge is how to conceptualize and measure electoral competitiveness at the district level across alternative electoral systems. Recent efforts to meet this challenge have introduced general measures of competitiveness which rest on explicit calculations about how votes translate into seats, but also implicit assumptions about how effort maps into votes (and how costly effort is). We investigate how assumptions about the effort-to-votes mapping affect the units in which competitiveness is best measured, arguing in favor of vote-share-denominated measures and against vote-share-per-seat measures. Whether elections under multimember proportional representation systems are judged more or less competitive than single-member plurality or runoff elections depends directly on the units in which competitiveness is assessed (and hence on assumptions about how effort maps into votes).
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.