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Dr. Tom Beauchamp wrote multiple seminal articles that influenced bioethics, research ethics, and animal ethics. But his influence extends beyond his academic scholarship. Here we honor Dr. Beauchamp’s contributions as a scholar, mentor, and teacher.
The excavation of a stratified sequence of deposits spanning the Initial Late Formative period (250 BC–AD 120) at Iruhito, in the upper Desaguadero Valley of Bolivia, provides insight into this previously unrecognized, four-century period separating the well-documented Middle Formative (800–250 BC) from the Late Formative (~AD 120–590) period. By tracking subtle shifts in ceramic, architectural, lithic, and faunal data, we can explore tempos of change in social life during this dynamic time. These data lead us to suggest that, rather than being a “transitional” period or a “hiatus” in regional occupation, the Initial Late Formative period was a distinct mode of sociality characterized by the realignment and expansion of interaction networks, on the one hand, and rejection of the decorative aesthetics, monumentality, and public-oriented performances of earlier periods, on the other. We argue that the Late Formative period centers emerging after ~AD 120 intentionally cited architecture and aesthetics that were distant in time and space, constituting a sophisticated political strategy. Finally, these data suggest that the chronological schemata we use to build regional histories often obscure social variability.
Cannabis use and familial vulnerability to psychosis have been associated with social cognition deficits. This study examined the potential relationship between cannabis use and cognitive biases underlying social cognition and functioning in patients with first episode psychosis (FEP), their siblings, and controls.
Methods
We analyzed a sample of 543 participants with FEP, 203 siblings, and 1168 controls from the EU-GEI study using a correlational design. We used logistic regression analyses to examine the influence of clinical group, lifetime cannabis use frequency, and potency of cannabis use on cognitive biases, accounting for demographic and cognitive variables.
Results
FEP patients showed increased odds of facial recognition processing (FRP) deficits (OR = 1.642, CI 1.123–2.402) relative to controls but not of speech illusions (SI) or jumping to conclusions (JTC) bias, with no statistically significant differences relative to siblings. Daily and occasional lifetime cannabis use were associated with decreased odds of SI (OR = 0.605, CI 0.368–0.997 and OR = 0.646, CI 0.457–0.913 respectively) and JTC bias (OR = 0.625, CI 0.422–0.925 and OR = 0.602, CI 0.460–0.787 respectively) compared with lifetime abstinence, but not with FRP deficits, in the whole sample. Within the cannabis user group, low-potency cannabis use was associated with increased odds of SI (OR = 1.829, CI 1.297–2.578, FRP deficits (OR = 1.393, CI 1.031–1.882, and JTC (OR = 1.661, CI 1.271–2.171) relative to high-potency cannabis use, with comparable effects in the three clinical groups.
Conclusions
Our findings suggest increased odds of cognitive biases in FEP patients who have never used cannabis and in low-potency users. Future studies should elucidate this association and its potential implications.
Knowledge of Ascophyllum nodosum extracts (ANEs) is still limited to avocado ‘Hass’ in the tropics. The objective of this study was to evaluate the effects of two ANEs application methods (foliar v. drench) at four different doses (0, 2.5, 5 and 7.5 ml/l) on the physiological response of three different avocado stages (seedlings and young and adult trees). Foliar or drench ANEs applications were performed monthly for all plants for 16 weeks. The evaluated variables were recorded at 4 and 20 weeks after the start of treatment (WAT). The results showed that ANEs can be applied to the drench or foliar method at doses ≥5 ml/l in the different growth stages evaluated. In seedlings, foliar or drench ANEs applications increased total dry weight (34.5 and 57.9 g for 0 and ≥5 ml/l, respectively) and stomatal conductance (gs) (380 and 205 mmol/m2s for 0 and ≥5 ml/l, respectively) at 20 WAT. In young trees, both application methods also improved growing index (88.6 and 102 cm for 0 and ≥5 ml/l, respectively) and gs (516 and 636 mmol/m2s for 0 and ≥5 ml/l, respectively) at the last sampling point. Adult trees showed that foliar or drench applications at higher doses also caused an increase in fruit yield (3.4 and 8.7 kg/tree for 0 and ≥5 ml/l, respectively) at 20 WAT. In conclusion, the use of foliar and soil ANEs applications at higher doses (≥5 ml/l) can be considered for integrated crop management of ‘Hass’ avocado.
Coastal wetlands are hotspots of carbon sequestration, and their conservation and restoration can help to mitigate climate change. However, there remains uncertainty on when and where coastal wetland restoration can most effectively act as natural climate solutions (NCS). Here, we synthesize current understanding to illustrate the requirements for coastal wetland restoration to benefit climate, and discuss potential paths forward that address key uncertainties impeding implementation. To be effective as NCS, coastal wetland restoration projects will accrue climate cooling benefits that would not occur without management action (additionality), will be implementable (feasibility) and will persist over management-relevant timeframes (permanence). Several issues add uncertainty to understanding if these minimum requirements are met. First, coastal wetlands serve as both a landscape source and sink of carbon for other habitats, increasing uncertainty in additionality. Second, coastal wetlands can potentially migrate outside of project footprints as they respond to sea-level rise, increasing uncertainty in permanence. To address these first two issues, a system-wide approach may be necessary, rather than basing cooling benefits only on changes that occur within project boundaries. Third, the need for NCS to function over management-relevant decadal timescales means methane responses may be necessary to include in coastal wetland restoration planning and monitoring. Finally, there is uncertainty on how much data are required to justify restoration action. We summarize the minimum data required to make a binary decision on whether there is a net cooling benefit from a management action, noting that these data are more readily available than the data required to quantify the magnitude of cooling benefits for carbon crediting purposes. By reducing uncertainty, coastal wetland restoration can be implemented at the scale required to significantly contribute to addressing the current climate crisis.
Crisis resolution teams (CRTs) are a crucial component of mental health care, providing timely support to individuals experiencing acute mental health crises. This abstract delves into the concept of crisis and seeks to identify the patients who stand to benefit from these specialized services.
Objectives
Defining crisis within the context of CRTs can be complex. It encompasses not only immediate emergencies but also broader mental health distress.
Research suggests that suitable candidates for CRT interventions are those facing acute mental health crises : This includes individuals experiencing suicidal ideation, severe agitation, or severe emotional distress.
La “Escala de Evaluación de Resolución de Crisis” (Crisis Resolution Team Assessment Tool, CRTAT) de Sonia Johnson es una herramienta diseñada para para medir la efectividad de los CRT y la duración de la intervención en crisis. Establece un límite de seis semanas como el período máximo durante el cual se debe ofrecer la atención en crisis.
Existen otras escalas de evaluación para medir la eficacia de la resolución de crisis:
1.Escala de Intensidad de Crisis (CIS): se utiliza para medir la gravedad de la crisis y la necesidad de intervención inmediata.
2.Escala de Evaluación de Crisis de Brage Hansen (BCES): se enfoca en la evaluación de crisis suicidas y evalúa la intensidad de la ideación suicida y la urgencia de la intervención.
3.Escala de Evaluación de Crisis de Eriksson (ECAS): Diseñada para evaluar la intensidad de la crisis en pacientes psiquiátricos, la ECAS se centra en la agitación, la ansiedad y la angustia emocional.
Methods
- Studies have explored the effectiveness of CRTs and the perspectives of service users. Understanding how patients perceive crisis and CRT services is crucial for tailoring interventions effectively.
Results
Conclusions
- CRTs play a vital role in mental health care, offering timely support to individuals experiencing crises. While defining crisis is complex, suitable candidates often include those in acute distress requiring immediate intervention. Understanding the perspectives of service users and the diverse nature of crisis experiences informs effective crisis resolution strategies.
“Cluster suicides,” also known as “suicide clusters,” refer to a phenomenon in which a series of suicides occur within a specific community, group, or geographic area within a relatively short period of time. These suicides often appear to be interconnected, either through imitation or contagion, and may involve individuals who have some form of social or emotional connection to each other.
Objectives
- Understanding the definition and characteristics of cluster suicides.
- Analyzing common risk factors and triggers in cluster suicide cases.
- Evaluating prevention and support strategies for affected individuals and communities.
Methods
We conduct an analysis of this concept based on a sample of suicides that occurred in a Spanish region over an 8-year period (2015-2022).
We will Analyzethe following aspects:
- Definition and characteristics of cluster suicides.
- Risk factors contributing to the occurrence of cluster suicides.
- Examples of real cases or case studies illustrating this phenomenon.
- The role of imitation and contagion in cluster suicides.
- Prevention and support strategies, including education on warning signs and access to mental health services.
- The impact of media coverage and how it can amplify the contagion effect.
- Measures to reduce access to lethal means of suicide.
Results
We will discuss about the results found:
- Definition and characteristics of cluster suicides.
- Risk factors contributing to the occurrence of cluster suicides.
- Examples of real cases or case studies illustrating this phenomenon.
- The role of imitation and contagion in cluster suicides.
- Prevention and support strategies, including education on warning signs and access to mental health services.
- The impact of media coverage and how it can amplify the contagion effect.
- Measures to reduce access to lethal means of suicide.
Conclusions
The main conclusions of our presentation are :
- The importance of recognizing cluster suicides as a real and concerning phenomenon.
- The need to address specific risk factors and triggers in affected communities.
- The effectiveness of prevention and support strategies in reducing cluster suicide cases.
- The importance of promoting media responsibility in suicide coverage.
BIBLIOGRAPHY
1.Cluster Suicides: A Critical Review and Theoretical Framework” (2019) - Este estudio proporciona una revisión crítica de la literatura sobre cluster suicides y presenta un marco teórico para comprender mejor este fenómeno
2.“Clusters of Suicides and Suicide Attempts: Identification, Prediction, and Prevention” (2016) - Aunque este estudio no se centra exclusivamente en España, ofrece información sobre la identificación y prevención de clusters de suicidio que puede ser relevante.
3.“Epidemiology of Suicide in Spain, 1981–2008” (2012) - Proporciona una visión general de la epidemiología del suicidio en España, lo que podría ayudar a contextualizar los estudios específicos sobre clusters.
Sexual unwellness (SU) has been linked to a lack of sexual satisfaction and to an incapacity to maintain sexual relations.
Objectives
The objective of this cross-cultural study is to shed light on older adults’ perspectives on SU across cultures.
Methods
Eighty-three older participants (65 to 98 years of age) took part in this qualitative study. Participants lived in the community and were of two different nationalities (Portuguese and Mexican). Semi-structured interviews were conducted, and content analysis was then carried out.
Results
SU emerged in the findings of the content analysis through six themes: Dissatisfying Sexual Experiences; Feelings of Isolation; Spirituality; Medication; Unattractiveness and Pain. The most common theme among older Portuguese participants was ‘Dissatisfying Sexual Experiences’ (25.5%). ‘Feelings of Isolation’ was most common among older Mexican participants (13.7%).
Conclusions
A diversity of experiences of older adults in relation to SU was highlighted in this study. Moreover, cross-cultural research on the construct of SU is essential for understanding the cultural differences in the conceptualization of the construct and how these themes may influence the quality of sexual life in old age.
The goal of this chapter is to show the reader a systematic approach to the assessment and treatment of aggression and violence arising from psychosis and a review of evidence-based pharmacological interventions for aggression and violence arising from impulsivity in the context of traumatic brain injury or neurocognitive disorder. In turn, we consider an algorithmic approach to the assessment and treatment of psychotically driven aggression and violence, the approach to treatment-resistance in schizophrenia spectrum disorders, data-supported treatment of aggression and violence related to traumatic brain injury, and, finally, data-supported pharmacological treatment of aggression and violence in the context of major neurocognitive disorder.
This commentary takes up a challenge posed by Franklin Miller in a 2022 essay in Bioethics Forum. Dr. Miller queried whether bioethicists could be useful in public health policy contexts and while he refrained from issuing an ultimate opinion, did identify several challenges to such utility. The current piece responds to the challenges Dr. Miller identifies and argues that with appropriate training, public health ethicists can be of service in virtually any context in which public health policies are deliberated and decided.
There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior IgG anti-receptor-binding domain (RBD) and neutralization response against the Alpha and Delta variants when administered to individuals with a previous infection by SARS-CoV-2. The booster dose spiked the neutralization activity among individuals with and without a prior SARS-CoV-2 infection. The ChAdOx1-S vaccine induced weaker antibody responses in infection-naive subjects. A follow-up of 4 months post-vaccination showed a drop in antibody titre, with about 20% of the infection-naive and 100% of SARS-CoV-2 pre-exposed participants with detectable neutralization capacity against Alpha pseudovirus (Alpha-PV) and Delta PV (Delta-PV). Our observations support the use of different vaccines in a country with high seroprevalence at the vaccination time.
Social support may protect against Alzheimer’s disease and related dementias (ADRD), potentially through emotional or instrumental support elements. Black and Hispanic/Latinx older adults bear a disproportionate burden of ADRD. However, independent effects of emotional and instrumental support on cognition, a primary indicator of ADRD risk, are largely understudied in these groups. Guided by the differential vulnerability hypothesis – the theoretical framework which posits that systemic racism disadvantages Black and Hispanic/Latinx individuals’ health – we hypothesize that emotional and instrumental support may be particularly important to protect against worse cognition for Black and Hispanic/Latinx older adults, who often have fewer resources due to these inequalities (e.g., wealth, educational opportunities) to otherwise maintain health. Using the NIH Toolbox Emotion Module measures of emotional (e.g., the extent to which individuals can rely on others in challenging times) and instrumental support (e.g., the extent to which individuals can rely on others for assistance in daily activities), we aimed to identify positive social support factors (i.e., emotional and instrumental support) that may protect against ADRD risk (i.e., longitudinal executive function and memory performance) among Black and Hispanic/Latinx older adults.
Participants and Methods:
Participants were 362 Black and 265 Hispanic/Latinx adults aged 65-89 (63% female, average age=75) from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study who completed baseline and up to two additional waves of assessments (every 1.5 years), including questionnaires, neuropsychological evaluations, and the NIH toolbox. Predictors included baseline covariates (i.e., age, language of test administration, gender, education, income, self-rated health) and NIH toolbox emotional and instrumental support variables. Outcomes were baseline and longitudinal memory (visual and verbal episodic memory) and executive functioning (verbal fluency and working memory) composites from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent growth curve models were conducted separately in Black and Hispanic/Latinx participants to estimate effects of emotional and instrumental support on baseline cognition and subsequent change in each domain.
Results:
Black participants reported greater emotional support. There were no group differences in levels of instrumental support. Greater instrumental support was associated with better initial memory (standardized β= .194, 95%CI: [.063, .325]) among Black participants but not among Hispanic/Latinx participants. In Hispanic/Latinx participants, greater emotional support was associated with better initial executive functioning (standardized β= .215, 95%CI: [.079, .350]. Emotional support was not associated with either cognitive domain in Black participants. There were no associations between emotional or instrumental support on cognitive change in either group.
Conclusions:
Results point to differences between Black and Hispanic/Latinx older adults in the impact of specific aspects of social support on different cognitive domains. Positive associations between instrumental support and baseline memory in Black participants and between emotional support and executive functioning in Hispanic/Latinx participants suggest unique cognitive consequences of social support across groups. Differences in the role of specific types of social supports may be useful in identifying intervention targets specifically for Black and Hispanic/Latinx older adults, who are disproportionately affected by ADRD. Future research will examine these constructs using multiple group models to test these associations more rigorously.
Major depressive disorder (MDD) is one of the leading causes of disability. We aimed to report the MDD-attributable prevalence, incidence and years lived with disability (YLDs) in the Middle East and North Africa (MENA) region from 1990 to 2019 by age, sex and socio-demographic index (SDI).
Methods:
Publicly available data on the burden of MDD were retrieved from the Global Burden of Disease (GBD) study 2019 for the 21 countries in MENA. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals.
Results:
In 2019, MDD had an age-standardised point prevalence of 3322.1 and an incidence rate of 4921.7 per 100,000 population in MENA. Furthermore, there were 4.1 million YLDs in 2019. However, there were no substantial changes in the MDD burden over the period 1990–2019. In 2019, Palestine had the highest burden of MDD. The highest prevalence, incidence and YLDs attributable to MDD were found in the 35–39 age group. In 2019, the YLD rate in MENA was higher than the global rate for almost all age groups. Furthermore, there was a broadly negative association between the YLD rate and SDI.
Conclusion:
The study highlights the need to prevent the disorder using a multidisciplinary approach and for the provision of cost-effective treatments for those affected, in order to increase their quality of life.
Childhood adversity is common and associated with elevated risk for transdiagnostic psychopathology. Reward processing has been implicated in the link between adversity and psychopathology, but whether it serves as a mediator or moderator is unclear. This study examined whether alterations in behavioral and neural reward processing function as a mechanism or moderator of psychopathology outcomes following adversity experiences, including threat (i.e., trauma) and deprivation. A longitudinal community sample of 10–15-year-old youths was assessed across two waves (Wave 1: n = 228; Wave 2: n = 206). Wave 1 assessed adverse experiences, psychopathology symptoms, reward processing on a monetary incentive delay task, and resting-state fMRI. At Wave 2, psychopathology symptoms were reassessed. Greater threat experiences were associated with blunted behavioral reward sensitivity, which, in turn, predicted increases in depression symptoms over time and mediated the prospective association between threat and depression symptoms. In contrast, reward sensitivity moderated the association between deprivation experiences and prospective externalizing symptoms such that the positive association of deprivation with increasing externalizing symptoms was absent for children with high levels of reward sensitivity.
This study examined the incorporation of benzalkonium chloride into palygorskite and montmorillonite, assessing their potential as drug carriers. The aim was to evaluate the use of both clay minerals as viable options for antibacterial drug delivery. Various amounts (0.5, 1.0 and 2.0 times the cation-exchange capacity) of benzalkonium chloride were incorporated into both clay minerals, and the resulting materials were characterized using Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction and elemental analysis using both CHNS-O elemental analysis and energy-dispersive X-ray spectroscopy. The Fourier-transform infrared spectroscopy and elemental analysis results indicate that benzalkonium chloride was incorporated successfully into the clay minerals. The X-ray diffraction traces of organo-montmorillonite indicate that the d-value increased as benzalkonium chloride content increased, confirming the intercalation of benzalkonium chloride within the montmorillonite interlayer space. By contrast, this behaviour was not observed for palygorskite. For the benzalkonium chloride-release studies, an initial burst release was found within the first 5 h, followed by a sustained release of benzalkonium chloride during the remaining testing time (24 h). Drug-release profiles were similar for modified palygorskite or montmorillonite during the testing time (24 h). Both clay minerals modified with benzalkonium chloride are promising materials for use as antibacterial fillers for several applications, including in the dental care industry.
Dementia within the criminal system, from arrest through incarceration, has been largely ignored. While the health system has begun grappling with the chronic conditions that will accompany an aging society, the criminal system has yet to meaningfully respond. Dementia is a clinical syndrome characterized by impairment in cognitive domains (memory, executive function, visuospatial). Additionally, dementia often includes behavioral symptoms that increase the likelihood that an individual’s actions may violate social norms and in some circumstances be deemed criminal. Prior studies have established criminal behavior as a trend among individuals living with dementia. Yet, the criminal system has yet to establish protections for individuals who commit a crime while impaired by dementia. This paper will report on an empirical study to evaluate the treatment of persons with dementia within the criminal justice system. We will report on interviews with attorneys (n=15) regarding their experience and perspective on the treatment of persons with dementia post-arrest. In the paper, we will explore topics identified through these interviews including pre-trial release, competency, placement (housing), criminal liability determination, sentencing, and post-conviction release. We will highlight key findings including the lack of a systematic screening process for dementia post-arrest, placement is a significant challenge, attorneys’ lack of training on dementia to be able to understand how the disease could impact decision-making, and the two legal mechanisms available to divert miss the mark given their focus on psychiatric populations. We will use these data and findings to argue for a research and policy agenda to address a gap in legal policies to appropriately manage persons with dementia post-arrest.
The use of antipsychotics (APS) is essential. Despite their great efficacy, some of them are associated with an increase in prolactin levels that can lead to hormonal changes needing to be identified and managed [1,2,3]. Hormonal changes use to have clinical implications including hypogonadism, infertility and sexual dysfunction
Objectives
To evaluate possible hormonal alterations and some clinical implications produced by hyperprolactinemia (HPRL) derived from the use of some antipsychotic compounds.
Methods
A complete fasting blood test was performed on a sample of 113 subjects (69 men and 44 women). 54% (n = 61) showed a normal prolactin level and 46% (n = 52) showed hyperprolactinaemia ( >50ng / ml). On the global sample, 39.8% (n = 45) was treated with some hyperprolactinemic drug , mostly risperidone and paliperidone.
Results
Some differences were found depending on the gender of the subjects. A highly significant inverse relationship between the values of prolactin and testosterone was found in males (p=0.020, r=-0.285). In females, increased prolactin level was significantly related to decreased cortisol values.
Conclusions
Antipsychotic-related Hyperprolactinaemia ( mainly risperidone and paliperidone) is related with a decrease in testosterone levels in males and with an increase in cortisol levels in females.
Psychiatric illnesses are related with a reduced life expectancy and an increase of mortality rates (around 60%) mainly associated with cardiovascular diseases [1]. The high prevalence of obesity, metabolic syndrome, diabetes mellitus and tobacco use among these patients undoubtelly predispose to the impairment in physical health and mortaility increase. Regular physical activity in the general population is associated with a decrease in cardiovascular risk but litle is know about iss influence in some chronic and severe mental disorders like schizophrenia [2].
Objectives
To quantify the physical activity performed by a sample of subjects with psychosis, borth males and female, compared to a control group.
Methods
A sample composed of 141 patients with schizoprenia was compared to 103 healthy subjects as a control group. The International Physical Activity Questionnaire - Short Form (IPAQ) scale was applied to all participants. The time (minutes) of physical activity performed in a week (METs) was collected by each participant [3].
Results
The differences in the total physical activity Mets for the patients with schizophrenia were highly significant (p = 0.001), showing a lower degree of physical activity compared to the control group. A higher and significant percentage of sedentary lifestyle among the psychiatric group (64.5%), compared to 35.5% in the control group was found.
Conclusions
The group of pateints with Schizophrenia showed a significant higher sedentary lifestile including less physical activity. This finding could be highly related with a higher risk of cardiovascular disease and deterioration of the physical health.
The prevalence of depression based on the Patient Health Questionnaire-8 (PHQ-8) may vary depending on the scoring method.
Objectives
1) To describe the prevalence of depression in Europe using two PHQ-8 scoring methods. 2) To identify the countries with the highest prevalence according to each method.
Methods
Data from 27 countries included in the European Health Survey (EHIS-2) for the year 2014/2015 were used (n=258,888). All participants who completed the PHQ-8 were included. The prevalence of depression and its 95% Confidence Interval (95%CI) were calculated overall for the whole of Europe and for each country using a PHQ-8≥10 cut-off point and the PHQ-8 algorithm scoring method. Weights derived from the complex sample design were considered for their calculation.
Results
The overall prevalence of depression for all Europe was lower using the PHQ-8>=10 cut-off point (6.38%, 95%CI 6.24-6.52) than the PHQ-8 algorithm (7.01%, 95%CI, 6.86-7.16). Using the PHQ-8≥10 cut-off point, the highest prevalence was observed in Iceland (10.33%, 95%CI, 9.33-11.32), Luxembourg (9.74%, 95%CI, 8.76-10.72) and Germany (9.24%, 95%CI, 8.82-9.66). Using the PHQ-8 algorithm the highest rates were observed in Hungary (10.99%, 95%CI,10.14-11.84), Portugal (10.63%, 95%CI, 9.96-11.29) and Iceland (9.80%, 95%CI, 8.77-10.83).
Conclusions
There is variability in the prevalence of depression rates in Europe according to the PHQ-8 scoring method. These findings suggest the necessity of identify the method of choice for each country comparing with a gold standard measure (clinical diagnosis). Countries with consistent higher prevalence of depression based on PHQ-8 regardless of scoring method deserve further study.