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Cannabis use has been linked to psychotic disorders but this association has been primarily observed in the Global North. This study investigates patterns of cannabis use and associations with psychoses in three Global South (regions within Latin America, Asia, Africa and Oceania) settings.
Methods
Case–control study within the International Programme of Research on Psychotic Disorders (INTREPID) II conducted between May 2018 and September 2020. In each setting, we recruited over 200 individuals with an untreated psychosis and individually-matched controls (Kancheepuram India; Ibadan, Nigeria; northern Trinidad). Controls, with no past or current psychotic disorder, were individually-matched to cases by 5-year age group, sex and neighbourhood. Presence of psychotic disorder assessed using the Schedules for Clinical Assessment in Neuropsychiatry and cannabis exposure measured by the World Health Organisation Alcohol, Smoking and Substance Involvement Screening Test (ASSIST).
Results
Cases reported higher lifetime and frequent cannabis use than controls in each setting. In Trinidad, cannabis use was associated with increased odds of psychotic disorder: lifetime cannabis use (adj. OR 1.58, 95% CI 0.99–2.53); frequent cannabis use (adj. OR 1.99, 95% CI 1.10–3.60); cannabis dependency (as measured by high ASSIST score) (adj. OR 4.70, 95% CI 1.77–12.47), early age of first use (adj. OR 1.83, 95% CI 1.03–3.27). Cannabis use in the other two settings was too rare to examine associations.
Conclusions
In line with previous studies, we found associations between cannabis use and the occurrence and age of onset of psychoses in Trinidad. These findings have implications for strategies for prevention of psychosis.
Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.
Methods:
We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.
Results:
BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.
Conclusions:
We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
To monitor for drug-related cardiac arrhythmias, psychiatrists regularly perform and interpret 12-lead (12L) and, increasingly often, six-lead (6L) electrocardiograms (ECGs). It is not known how training on this complex skill is updated or how well psychiatrists can interpret relevant arrhythmias on either device.
We conducted an online survey and ECG interpretation test of cardiac rhythms relevant to psychiatrists.
A total of 183 prescribers took part; 75% did not regularly update their ECG interpretation skills, and only 22% felt confident in interpreting ECGs. Most participants were able to recognise normal ECGs. For both 6L and 12L ECGs, the majority of participants were able to recognise abnormal ECGs, but fewer than 50% were able to correctly identify relevant arrhythmias (complete heart block and long QTc). A small number prescribed in the presence of potentially fatal arrhythmias. These findings suggest a need for mandatory ECG interpretation training to improve safe prescribing practice.
Extensive evidence indicates that rates of psychotic disorder are elevated in more urban compared with less urban areas, but this evidence largely originates from Northern Europe. It is unclear whether the same association holds globally. This study examined the association between urban residence and rates of psychotic disorder in catchment areas in India (Kancheepuram, Tamil Nadu), Nigeria (Ibadan, Oyo), and Northern Trinidad.
Methods
Comprehensive case detection systems were developed based on extensive pilot work to identify individuals aged 18–64 with previously untreated psychotic disorders residing in each catchment area (May 2018–April/May/July 2020). Area of residence and basic demographic details were collected for eligible cases. We compared rates of psychotic disorder in the more v. less urban administrative areas within each catchment area, based on all cases detected, and repeated these analyses while restricting to recent onset cases (<2 years/<5 years).
Results
We found evidence of higher overall rates of psychosis in more urban areas within the Trinidadian catchment area (IRR: 3.24, 95% CI 2.68–3.91), an inverse association in the Nigerian catchment area (IRR: 0.68, 95% CI 0.51–0.91) and no association in the Indian catchment area (IRR: 1.18, 95% CI 0.93–1.52). When restricting to recent onset cases, we found a modest positive association in the Indian catchment area.
Conclusions
This study suggests that urbanicity is associated with higher rates of psychotic disorder in some but not all contexts outside of Northern Europe. Future studies should test candidate mechanisms that may underlie the associations observed, such as exposure to violence.
Depression in dementia is common, disabling and causes significant distress to patients and carers. Despite widespread use of antidepressants for depression in dementia, there is no evidence of therapeutic efficacy, and their use is potentially harmful in this patient group. Depression in dementia has poor outcomes and effective treatments are urgently needed. Understanding why antidepressants are ineffective in depression in dementia could provide insight into their mechanism of action and aid identification of new therapeutic targets. In this review we discuss why depression in dementia may be a distinct entity, current theories of how antidepressants work and how these mechanisms of action may be affected by disease processes in dementia. We also consider why clinicians continue to prescribe antidepressants in dementia, and novel approaches to understand and identify effective treatments for patients living with depression and dementia.
Three experiments (N = 550) examined the effect of an interval construction elicitation method used in several expert elicitation studies on judgment accuracy. Participants made judgments about topics that were either searchable or unsearchable online using one of two order variations of the interval construction procedure. One group of participants provided their best judgment (one step) prior to constructing an interval (i.e., lower bound, upper bound, and a confidence rating that the correct value fell in the range provided), whereas another group of participants provided their best judgment last, after the three-step confidence interval was constructed. The overall effect of this elicitation method was not significant in 8 out of 9 univariate tests. Moreover, the calibration of confidence intervals was not affected by elicitation order. The findings warrant skepticism regarding the benefit of prior confidence interval construction for improving judgment accuracy.
Individuals often assess themselves as being less susceptible to common biases compared to others. This bias blind spot (BBS) is thought to represent a metacognitive error. In this research, we tested three explanations for the effect: The cognitive sophistication hypothesis posits that individuals who display the BBS more strongly are actually less biased than others. The introspection bias hypothesis posits that the BBS occurs because people rely on introspection more when assessing themselves compared to others. The conversational processes hypothesis posits that the effect is largely a consequence of the pragmatic aspects of the experimental situation rather than true metacognitive error. In two experiments (N = 1057) examining 18 social/motivational and cognitive biases, there was strong evidence of the BBS. Among the three hypotheses examined, the conversational processes hypothesis attracted the greatest support, thus raising questions about the extent to which the BBS is a metacognitive effect.
Many decisions in everyday life involve a choice between exploring options that are currently unknown and exploiting options that are already known to be rewarding. Previous work has suggested that humans solve such “explore-exploit” dilemmas using a mixture of two strategies: directed exploration, in which information seeking drives exploration by choice, and random exploration, in which behavioral variability drives exploration by chance. One limitation of this previous work was that, like most studies on explore-exploit decision making, it focused exclusively on the domain of gains, where the goal was to maximize reward. In many real-world decisions, however, the goal is to minimize losses and it is well known from Prospect Theory that behavior can be quite different in this domain. In this study, we compared explore-exploit behavior of human subjects under conditions of gain and loss. We found that people use both directed and random exploration regardless of whether they are exploring to maximize gains or minimize losses and that there is quantitative agreement between the exploration parameters across domains. Our results also revealed an overall bias towards the more uncertain option in the domain of losses. While this bias towards uncertainty was qualitatively consistent with the predictions of Prospect Theory, quantitatively we found that the bias was better described by a Bayesian account, in which subjects had a prior that was optimistic for losses and pessimistic for gains. Taken together, our results suggest that explore-exploit decisions are driven by three independent processes: directed and random exploration, and a baseline uncertainty seeking that is driven by a prior.
HIV and severe wasting are associated with post-discharge mortality and hospital readmission among children with complicated severe acute malnutrition (SAM); however, the reasons remain unclear. We assessed body composition at hospital discharge, stratified by HIV and oedema status, in a cohort of children with complicated SAM in three hospitals in Zambia and Zimbabwe. We measured skinfold thicknesses and bioelectrical impedance analysis (BIA) to investigate whether fat and lean mass were independent predictors of time to death or readmission. Cox proportional hazards models were used to estimate the association between death/readmission and discharge body composition. Mixed effects models were fitted to compare longitudinal changes in body composition over 1 year. At discharge, 284 and 546 children had complete BIA and skinfold measurements, respectively. Low discharge lean and peripheral fat mass were independently associated with death/hospital readmission. Each unit Z-score increase in impedance index and triceps skinfolds was associated with 48 % (adjusted hazard ratio 0·52, 95 % CI (0·30, 0·90)) and 17 % (adjusted hazard ratio 0·83, 95 % CI (0·71, 0·96)) lower hazard of death/readmission, respectively. HIV-positive v. HIV-negative children had lower gains in sum of skinfolds (mean difference −1·49, 95 % CI (−2·01, −0·97)) and impedance index Z-scores (–0·13, 95 % CI (−0·24, −0·01)) over 52 weeks. Children with non-oedematous v. oedematous SAM had lower mean changes in the sum of skinfolds (–1·47, 95 % CI (−1·97, −0·97)) and impedance index Z-scores (–0·23, 95 % CI (−0·36, −0·09)). Risk stratification to identify children at risk for mortality or readmission, and interventions to increase lean and peripheral fat mass, should be considered in the post-discharge care of these children.
The aim of this study was to use longitudinal population-based data to examine the associations between childhood sexual abuse (CSA) and risk for adverse outcomes in multiple life domains across adulthood. In 937 individuals followed from birth to age 45y, we assessed associations between CSA (retrospectively reported at age 26y) and the experience of 22 adverse outcomes in seven domains (physical, mental, sexual, interpersonal, economic, antisocial, multi-domain) from young adulthood to midlife (26 to 45y). Analyses controlled for sex, socioeconomic status, prospectively reported child harm and household dysfunction adverse childhood experiences, and adult sexual assault, and considered different definitions of CSA. After adjusting for confounders, CSA survivors were more likely than their peers to experience internalizing, externalizing, and thought disorders, suicide attempts, health risk behaviors, systemic inflammation, poor oral health, sexually transmitted diseases, high-conflict relationships, benefit use, financial difficulties, antisocial behavior, and cumulative problems across multiple domains in adulthood. In sum, CSA was associated with multiple persistent problems across adulthood, even after adjusting for confounding life stressors, and the risk for particular problems incremented with CSA severity. The higher risk for most specific problems was small to moderate, but the cumulative long-term effects across multiple domains reflect considerable individual and societal burden.
Sea-level science has seen many recent developments in observations and modelling of the different contributions and the total mean sea-level change. In this overview, we discuss (1) the evolution of the Intergovernmental Panel on Climate Change (IPCC) projections, (2) how the projections compare to observations and (3) the outlook for further improving projections. We start by discussing how the model projections of 21st century sea-level change have changed from the IPCC AR5 report (2013) to SROCC (2019) and AR6 (2021), highlighting similarities and differences in the methodologies and comparing the global mean and regional projections. This shows that there is good agreement in the median values, but also highlights some differences. In addition, we discuss how the different reports included high-end projections. We then show how the AR5 projections (from 2007 onwards) compare against the observations and find that they are highly consistent with each other. Finally, we discuss how to further improve sea-level projections using high-resolution ocean modelling and recent vertical land motion estimates.
There is evidence that the COVID-19 pandemic has negatively affected mental health, but most studies have been conducted in the general population.
Aims
To identify factors associated with mental health during the COVID-19 pandemic in individuals with pre-existing mental illness.
Method
Participants (N = 2869, 78% women, ages 18–94 years) from a UK cohort (the National Centre for Mental Health) with a history of mental illness completed a cross-sectional online survey in June to August 2020. Mental health assessments were the GAD-7 (anxiety), PHQ-9 (depression) and WHO-5 (well-being) questionnaires, and a self-report question on whether their mental health had changed during the pandemic. Regressions examined associations between mental health outcomes and hypothesised risk factors. Secondary analyses examined associations between specific mental health diagnoses and mental health.
Results
A total of 60% of participants reported that mental health had worsened during the pandemic. Younger age, difficulty accessing mental health services, low income, income affected by COVID-19, worry about COVID-19, reduced sleep and increased alcohol/drug use were associated with increased depression and anxiety symptoms and reduced well-being. Feeling socially supported by friends/family/services was associated with better mental health and well-being. Participants with a history of anxiety, depression, post-traumatic stress disorder or eating disorder were more likely to report that mental health had worsened during the pandemic than individuals without a history of these diagnoses.
Conclusions
We identified factors associated with worse mental health during the COVID-19 pandemic in individuals with pre-existing mental illness, in addition to specific groups potentially at elevated risk of poor mental health during the pandemic.
Monoclonal antibody therapeutics to treat coronavirus disease (COVID-19) have been authorized by the US Food and Drug Administration under Emergency Use Authorization (EUA). Many barriers exist when deploying a novel therapeutic during an ongoing pandemic, and it is critical to assess the needs of incorporating monoclonal antibody infusions into pandemic response activities. We examined the monoclonal antibody infusion site process during the COVID-19 pandemic and conducted a descriptive analysis using data from 3 sites at medical centers in the United States supported by the National Disaster Medical System. Monoclonal antibody implementation success factors included engagement with local medical providers, therapy batch preparation, placing the infusion center in proximity to emergency services, and creating procedures resilient to EUA changes. Infusion process challenges included confirming patient severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, strained staff, scheduling, and pharmacy coordination. Infusion sites are effective when integrated into pre-existing pandemic response ecosystems and can be implemented with limited staff and physical resources.