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Professor Keith Hawton hosted the 25th British Isles Research Workshop on Suicide and Self-harm in November 2018. An annually held event which brings together researchers from the UK, Ireland and other countries.
Socio-medical factors associated with neurodevelopmental disorders on the Kenyan coast.
Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism and intellectual disability. Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast. We included 172 study participants from the Kilifi Autism study and 151 from the NeuroDev study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression. Univariable analysis in the Kilifi Autism study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 [95%CI: 4.04, 27.41] for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, maternal bleeding) (OR=3.17 [95%CI: 1.61, 6.23]). In the NeuroDev study sample, labour and birth complications (OR=7.30 [95%CI 2.17, 24.61]), neonatal jaundice (OR=5.49 [95%CI 1.61,18.72]) and infection during pregnancy (OR= 5.31 [95%CI 1.56, 18.11]) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs. Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress of these children. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed.
The relationship between lifetime trauma exposure and psychosis in a multi-country case-control study in Africa
Background: Exposure to traumatic events is a known risk factor for psychosis. Additionally, psychosis may be a risk factor for exposure to traumatic events. There are little data on the relationship between traumatic events and psychosis in sub-Saharan Africa, particularly in large, cross-country samples using the same instrument. Methods: In a case-control study, 21,606 adults were recruited with psychosis (cases) and 21,329 adults without any history of psychosis (controls) in Ethiopia, Kenya, South Africa, and Uganda from 2018 to 2023 (n = 42,935). Lifetime trauma exposure was assessed using the Life Events Checklist-5. Regression models included the: i) prevalence of any trauma exposure; ii) cumulative burden of trauma exposure; and iii) the odds of exposure to specific trauma types. Analyses were run by case-control status for the full sample and within each country; trauma types endorsed by cases and controls were further stratified by sex. Results: There was a modest increased odds of trauma among cases compared with controls. Cases had higher odds of reporting exposure to ≥1 trauma and ≥3 trauma types (adjusted odds ratio (AOR) = 1.23, 95 % CI: 1.18–1.28 and AOR = 1.19, 95 % CI: 1.15–1.23, respectively). The trauma types with the highest odds were sexual violence (AOR = 1.99, 95 % CI: 1.86–2.14), physical violence (AOR = 1.69, 95 % CI: 1.62–1.76), and network trauma (causing injury, harm, or death to someone else) (AOR = 1.52, 95 % CI: 1.38–1.67). Similar trends were seen within each country. Sexual violence and physical violence were most endorsed by female cases and male cases, respectively. Network trauma was most endorsed by male cases and particularly from South Africa. Conclusion: People in eastern and southern Africa report significant exposure to trauma with a slightly higher prevalence among individuals with psychosis. Special attention should be paid to potential trauma exposure including interpersonal violence when providing treatment for this population.
"The traditional healer said, 'I had a genie that scared me in my eyes, and that is why I fall": An ethnographic study in Mahenge, Tanzania.
BACKGROUND: In many low-income countries, individuals with epilepsy often turn to traditional healers as their first source of treatment after the onset of seizures. However, their experiences with traditional healing practices remain poorly understood. This study examines the perceptions and experiences of people with epilepsy in relation to traditional healing in Mahenge, Tanzania. METHODS: A culturally specific ethnographic approach, centred on oral history, was employed to capture rich, contextually grounded narratives. A total of 45 oral history interviews were conducted with individuals living with epilepsy from 21 villages in Mahenge. Participants were purposively selected based on the following criteria: being at least 18 years of age, having a diagnosis of epilepsy, and the ability to recount their experiences in Swahili, the primary language spoken in the region. Data were manually analysed using thematic analysis. RESULTS: Traditional healers often attribute epilepsy to supernatural causes, such as curses or witchcraft, linking seizure onset to past events believed to have triggered the condition. Their treatment practices are frequently accompanied by strict behavioural restrictions, which can be challenging for individuals with epilepsy to follow and are sometimes cited as reasons for treatment failure. Moreover, some participants reported experiences of physical, emotional, and even sexual harassment during their encounters with traditional healers. CONCLUSION: There is a strong reliance on traditional healing practices for epilepsy, where cultural beliefs and rituals can hinder accurate diagnosis and effective care. Raising awareness about epilepsy, its medical management, and the rights of people with epilepsy, both among traditional healers and the broader community, is essential to improve care and protect the well-being of those affected.
A single dose of lamotrigine induces a positive memory bias in healthy volunteers.
BACKGROUND: Lamotrigine has been shown to be effective in the long-term treatment and relapse prevention of depression in bipolar disorder. However, the neuropsychological mechanisms underlying these effects are unclear. We investigated the effects of lamotrigine on a battery of emotional processing tasks in healthy volunteers, previously shown to be sensitive to antidepressant drug action in similar experimental designs. METHODS: Healthy volunteers (n = 36) were randomized in a double-blind design to receive a single dose of placebo or 300 mg lamotrigine. Mood and subjective effects were monitored throughout the study period, and emotional processing was assessed using the Oxford Emotional Test Battery (ETB) 3 hours post-administration. RESULTS: Participants receiving lamotrigine showed increased accurate recall of positive versus negative self-descriptors, compared to those in the placebo group. There were no other significant effects on emotional processing in the ETB, and lamotrigine did not affect ratings of mood or subjective experience. CONCLUSIONS: Lamotrigine did not induce widespread changes in emotional processing. However, there was increased positive bias in emotional memory, similar to the effects of antidepressants reported in previous studies. Further work is needed to assess whether similar effects are seen in the clinical treatment of patients with bipolar disorder and the extent to which this is associated with its clinical action in relapse prevention.
Results From a Long-Term Observational Follow-Up Study of a Single Dose of Psilocybin for a Treatment-Resistant Episode of Major Depressive Disorder.
Background: The largest randomized study of psilocybin to date demonstrated the efficacy of COMP360 25 mg (Compass Pathways' investigational proprietary pharmaceutical-grade synthesized psilocybin formulation) in participants with treatment-resistant depression (COMP 001), compared with 10 mg and 1 mg doses. Here, we report findings from COMP 004, a 52-week observational follow-up of patients from COMP 001 and COMP 003, a small open-label study of the coadministration of 25 mg COMP360 with continuing antidepressant treatment. Methods: Adverse events (AEs) were collected over the full 52-week period. The primary efficacy endpoint was time to a prespecified depressive event over the 52 weeks following COMP360 administration in COMP 001 participants, presented as Kaplan-Meier estimates. A post hoc analysis included only participants that entered COMP 004. Data were collected from July 2020 to July 2022. Results: Sixty-six participants entered COMP 004 (COMP 001, n = 58 [25 mg group n = 22, 10 mg group n = 19, 1 mg group n = 17]; COMP 003, n = 8). Few AEs were reported post-entry into COMP 004, with 1 AE of mild suicidal ideation in the 1 mg group deemed possibly related to study drug. For all COMP 001 patients (n = 233), median time to depressive event was greater for the 25 mg group (92 days) compared to the 10 mg (83 days) and 1 mg (62 days) groups, with the majority of participants having had a depressive event by Week 12 (25 mg n = 37/75, 10 mg n = 38/79, 1 mg n = 44/75). The post hoc supplementary analysis of those who enrolled in COMP 004 from COMP 001 exhibited the difference between groups more strikingly (25 mg, 189 days; 10 mg, 43 days; 1 mg, 21 days); however, only 10 participants experienced a depressive event post-COMP 004 enrollment (25 mg n = 6, 10 mg n = 3, 1 mg n = 1) from COMP 001 and none from COMP 003. At COMP 004 entry, the 1 mg group had the highest number of participants on antidepressant medication (n = 10; 10 mg, n = 9; 25 mg, n = 6) and generally initiated treatment earlier. Conclusion: Over 52 weeks, a single administration of 25 mg psilocybin suggested longer maintenance of antidepressant effect than both 1 mg and 10 mg. Larger long-term studies are required to confirm these findings and provide clarity on the longer-term effects of psilocybin. Trial Registration: ClinicalTrials.gov identifier: NCT04519957.
Achieving robust labeling above the circle of Willis with vessel-encoded arterial spin labeling.
PURPOSE: To improve the robustness of noninvasive vessel-selective perfusion imaging and angiography using vessel-encoded arterial spin labeling (VEASL) when applied to complex vascular geometries, such as above the circle of Willis (CoW) in the brain. METHODS: Our proposed improved optimized encoding scheme (IOES) better accounts for vascular geometry and the VEASL encoding process, leading to more SNR-efficient encodings than previous approaches. Pseudo-continuous arterial spin labeling (PCASL) parameters were optimized for a thinner labeling region, allowing tortuous vessels to be more accurately treated as single points within the labeling plane. Our optimized approach was compared to the original OES method above the CoW in healthy volunteers, with preliminary application in two Moyamoya patients. RESULTS: In simulation, the IOES improved SNR efficiency by approximately 10% and used longer wavelength encodings that are less sensitive to subject motion. The effective labeling thickness was reduced using optimized PCASL parameters, which maintained high labeling efficiency. In healthy volunteers, these improvements allowed for the separation of at least nine arteries and their downstream tissues, with more accurate vessel decoding and closer alignment between the measured VEASL signal modulation and the encoding design. Vascular territories consistent with angiography were found in the Moyamoya patients. CONCLUSIONS: Combining IOES with optimized PCASL parameters, the vessel-decoding efficacy in a region with complex vascular geometry above the CoW was improved. The automated encoding design process and scan times under 6 min make it feasible to observe flow patterns above the CoW in clinical settings, particularly for studies of collateral circulation.
How Should We Treat Farmed Animals? Adolescents Are More Speciesist Than Adults
Adults engage in psychological processes (including species-based categorisation and post-hoc reasoning) that result in ascribing high moral value to some animals while eating others. Do adolescents engage in similar processes? We compared adolescents’ (n = 89, M age = 13.54) and adults’ (n = 113, M age = 43.73) views on four measurements. Regarding moral judgements, we found that adolescents were (a) more speciesist than adults (i.e., believed moral worth was determined by species membership) and (b) reported that farmed animals ought to be treated less well than adults did. There were (c) no differences in how morally justified adults and adolescents found eating meat. Finally, we found that (d) adolescents were less likely than adults to report that in society, farmed animals are categorised as food rather than pets. Overall, this suggests that adolescents base their view on the treatment an individual deserves more on the species it belongs to than adults do, which may serve as a first attempt to make sense of the differential treatment different animals are subjected to in society.
Learning How to Improve the Treatment of Persecutory Delusions: Using a Principal Trajectories Analysis to Examine Differential Effects of Two Psychological Interventions (Feeling Safe, Befriending) in Distinct Groups of Patients.
BACKGROUND: A theory-driven cognitive therapy (Feeling Safe) has produced much better outcomes for patients with persecutory delusions. There are four distinct response classes: very high delusion conviction with large improvement, very high delusion conviction with no response, high delusion conviction with large improvement, and high delusion conviction with modest improvement. Our objective was to apply principal trajectories analysis, a novel statistical method, to original trial data to estimate whether these groups may have responded differently to a different intervention: befriending. DESIGN: One hundred and thirty patients with persistent persecutory delusions were randomised to six months of Feeling Safe or befriending. Baseline assessments were used to assign patients allocated to befriending (who did not receive Feeling Safe) into the four Feeling Safe response classes. The treatment effect, including on potential mediators, was then estimated for these classes. RESULTS: Patients in two treatment response classes (Very high conviction/large improvement, High conviction/large improvement) benefited more from Feeling Safe, patients in one group (Very high conviction/no improvement) benefited more from befriending, and patients in the remaining group (High conviction/moderate improvement) benefited equally from the interventions. Mechanism differences were detected when Feeling Safe was superior to befriending, but not when befriending was superior. CONCLUSIONS: There may be patients with psychosis who benefit more from one type of therapy than another, likely due to different change mechanisms. The application of principal trajectories has generated testable hypotheses and a potential step toward personalised treatment. We recommend an investigation of whether sequential provision of the treatment types could enhance patient outcomes. Keywords: persecutory, delusions, outcome trajectories, psychosis, cognitive therapy.
Reasoning to Justify Eating Animals Varies With Age.
The present study examined the justifications used by children, adolescents, and adults to justify eating animals. Children (n = 100, Mage = 9.82, SD = 0.77, female n = 49) as compared to adolescents (n = 76, Mage = 14.0, SD = 1.62, female n = 36) and adults (n = 113, Mage = 44.1, SD = 14.4, female n = 54) were more ambivalent or opposed to eating animals, and they showed a distinct reasoning pattern. Children relied less on arguments about meat eating being natural or with to humane slaughter practices. These findings align with recent theoretical perspectives that reasoning may be used to counter cognitive dissonance arising from knowledge of food production systems.
Comorbidities Are Associated With Unfavorable Outcome in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Exploratory Study From the CROCTINO Cohort.
BACKGROUND: Comorbidities occur in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD), potentially contributing to a less favorable disease course. OBJECTIVES: To characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4-NMOSD. METHODS: Four hundred and forty-two participants from the CROCTINO cohort were evaluated for comorbidities. RESULTS: In AQP4-NMOSD patients (n = 360), 43.5% (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) single and 25% (n = 5) multiple. In DN-NMOSD (n = 33), 36.4% (n = 12) had comorbidities equally split. AQP4-NMOSD patients had more multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4%, n = 65) than MOGAD (20%, n = 4, p = 0.09) and DN-NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4-NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN-NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN-NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4-NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs. 0.49 ± 0.98, p
Submaximal 2-day cardiopulmonary exercise testing to assess exercise capacity and post-exertional symptom exacerbation in people with long COVID.
Long COVID has a complex pathology and a heterogeneous symptom profile that impacts quality of life and functional status. Post-exertional symptom exacerbation (PESE) affects one-third of people living with long COVID, but the physiological basis of impaired physical function remains poorly understood. Sixty-eight people (age (mean ± SD): 50 ± 11 years, 46 females (68%)) were screened for severity of PESE and completed two submaximal cardiopulmonary exercise tests separated by 24 h. Work rate was stratified relative to functional status and was set at 10, 20 or 30 W, increasing by 5 W/min for a maximum of 12 min. At the first ventilatory threshold (VT1), V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ was 0.73 ± 0.16 L/min on Day 1 and decreased on Day 2 (0.68 ± 0.16 L/min; P = 0.003). Work rate at VT1 was lower on Day 2 (Day 1 vs. Day 2; 28 ± 13 vs. 24 ± 12 W; P = 0.004). Oxygen pulse on Day 1 at VT1 was 8.2 ± 2.2 mL/beat and was reduced on Day 2 (7.5 ± 1.8 mL/beat; P = 0.002). The partial pressure of end tidal carbon dioxide was reduced on Day 2 (Day 1 vs. Day 2; 38 ± 3.8 vs. 37 ± 3.2 mmHg; P = 0.010). Impaired V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ is indicative of reduced transport and/or utilisation of oxygen. V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ at VT1 was impaired on Day 2, highlighting worsened function in the 24 h after submaximal exercise. The data suggest multiple contributing physiological mechanisms across different systems and further research is needed to investigate these areas.