Impact of JQ1 treatment on seizures, hippocampal gene expression, and gliosis in a mouse model of temporal lobe epilepsy.

Epilepsy is a neurological disease characterised by recurrent seizures with complex aetiology. Temporal lobe epilepsy, the most common form in adults, can be acquired following brain insults including trauma, stroke, infection or sustained status epilepticus. The mechanisms that give rise to the formation and maintenance of hyperexcitable networks following acquired insults remain unknown, yet an extensive body of literature points towards persistent gene and epigenomic dysregulation as a potential mediator of this dysfunction. While much is known about the function of specific classes of epigenetic regulators (writers and erasers) in epilepsy, much less is known about the enzymes, which read the epigenome and modulate gene expression accordingly. Here, we explore the potential role for the epigenetic reader bromodomain and extra-terminal domain (BET) proteins in epilepsy. Using the intra-amygdala kainic acid model of temporal lobe epilepsy, we initially identified widespread dysregulation of important epigenetic regulators including EZH2 and REST as well as altered BRD4 expression in chronically epileptic mice. BRD4 activity was also notably affected by epilepsy-provoking insults as seen by elevated binding to and transcriptional regulation of the immediate early gene Fos. Despite influencing early aspects of epileptogenesis, blocking BET protein activity with JQ1 had no overt effects on epilepsy development in mice but did alter glial reactivity and influence gene expression patterns, promoting various neurotransmitter signalling mechanisms and inflammatory pathways in the hippocampus. Together, these results confirm that epigenetic reader activity is affected by epilepsy-provoking brain insults and that BET activity may exert cell-specific actions on inflammation in epilepsy.

Emotion dysregulation in nonsuicidal self-injury: Dissociations between global self-reports and real-time responses to emotional challenge.

INTRODUCTION: Prominent theories of nonsuicidal self-injury (NSSI) propose that the behaviour is characterised by amplified emotional responses. However, little is known about how people who self-injure respond during emotional challenge. METHODS: We measured subjective and physiological responding (heart rate, heart rate variability, and electrodermal responding) among young adults with past-year NSSI (n = 51) and those with no lifetime NSSI (n = 50) during a resting baseline, a stress induction, and a post-stress resting phase. Participants reported the extent to which they spontaneously used cognitive reappraisal and expressive suppression during the post-stress phase. Two weeks later, a subset of the sample (n = 42) reported how they remembered feeling during the laboratory session. RESULTS: Although the NSSI group reported considerably greater emotion dysregulation than Controls, both groups showed similar subjective and psychological reactivity to, and recovery from, emotional challenge. Both groups used reappraisal and suppression regulation strategies following acute stress to a similar extent, and later came to remember the emotional challenge in a similar manner. LIMITATIONS: Within the NSSI group, past-year self-injury tended to be infrequent and sporadic. Only 43.6% of the sample participated in the follow-up survey assessing memory of emotional challenge. CONCLUSIONS: Findings demonstrate that the role of emotion in NSSI is more complex than prominent theories can account for, raising substantial questions regarding the nature of emotion in NSSI. A more comprehensive understanding of the role of emotion in NSSI is needed to inform intervention strategies to better support people who self-injure.

Distinct profiles of mental health need and high need overall among New Zealand adolescents - Cluster analysis of population survey data.

OBJECTIVE: The objective was to identify clinically meaningful groups of adolescents based on self-reported mental health and wellbeing data in a population sample of New Zealand secondary school students. METHODS: We conducted a cluster analysis of six variables from the Youth19 Rangatahi Smart Survey (n = 7721, ages 13-18 years, 2019): wellbeing (World Health Organization Well-Being Index), possible anxiety symptoms (Generalized Anxiety Disorder 2-item, adapted), depression symptoms (short form of the Reynolds Adolescent Depression Scale) and past-year self-harm, suicide ideation and suicide attempt. Demographic, contextual and behavioural predictors of cluster membership were determined through multiple discriminant function analysis. We performed cross-validation analyses using holdout samples. RESULTS: We identified five clusters (n = 7083). The healthy cluster (n = 2855, 40.31%) reported positive mental health across indicators; the anxious cluster (n = 1994, 28.15%) reported high possible anxiety symptoms and otherwise generally positive results; the stressed and hurting cluster (n = 667, 9.42%) reported sub-clinical depression and possible anxiety symptoms and some self-harm; the distressed and ideating cluster (n = 1116, 15.76%) reported above-cutoff depression and possible anxiety symptoms and high suicide ideation; and the severe cluster (n = 451; 6.37%) reported the least positive mental health across indicators. Female, rainbow, Maori and Pacific students and those in higher deprivation areas were overrepresented in higher severity clusters. Factors including exposure to sexual harm and discrimination were associated with increasing cluster severity. CONCLUSION: We identified high prevalence of mental health challenges among adolescents, with distinct clusters of need. Youth mental health is not 'one size fits all'. Future research should explore youth behaviour and preferences in accessing support and consider how to best support the mental health of each cluster.

Who are we missing? Self-selection bias in nonsuicidal self-injury research.

BACKGROUND: Despite the threat of self-selection bias to the generalizability of research findings, remarkably little is known about who chooses to take part in non-suicidal self-injury (NSSI) research specifically. We aimed to establish the extent of willingness to take part in NSSI research within a commonly sampled population before assessing whether individual differences in demographic characteristics, NSSI lived experience, and participation experiences were associated with willingness to take part in future NSSI research. METHODS: New Zealand university students (n = 3098) completed self-report measures of their NSSI, psychological distress, emotional dysregulation, experience of their participation in the current study, and willingness to participate in future NSSI research. RESULTS: Most participants (78.2%) indicated that they were willing to take part in future NSSI research. Men, older participants, people with NSSI lived experience, and those with more frequent past-year NSSI were more likely to be willing to take part in future NSSI research. Participants who reported a more positive subjective experience of the current study also indicated greater willingness. CONCLUSIONS: Findings demonstrate systematic differences in who is willing to take part in NSSI research. Future research should implement methodological and statistical approaches to mitigate the impact of self-selection bias on NSSI research.

Emotional responding to overt and subtle social exclusion among young women who engage in non-suicidal self-injury.

People who engage in non-suicidal self-injury (NSSI) consistently report greater emotion reactivity and dysregulation than their peers. However, evidence that these self-reports reflect an amplified emotional response under controlled conditions is limited. Here we test the effects of both subtle and overt social exclusion, to determine whether self-reported emotion dysregulation reflects responses to real-time emotional challenge for people who self-injure. We recruited 100 young women with past-year NSSI and 100 without NSSI to an online experiment. Participants took part in a baseline social inclusion ball-tossing game, followed by either an overt or subtle social exclusion ball-tossing game, while we measured negative mood and belongingness. Despite reporting greater emotion reactivity (d = 1.40) and dysregulation (d = 1.63) than controls, women with past-year NSSI showed no differences in negative mood or belongingness ratings in response to either overt or subtle social exclusion. Within the NSSI group, exploratory analyses found greater endorsement of intrapersonal functions predicted greater negative mood following social exclusion (ß = 0.19). Given that amplified emotional responding is central to prominent theoretical models of NSSI, findings highlight the need to better understand the divergence in findings between self-reported emotion dysregulation and real-time emotional responding among people who self-injure.

Educational stakeholders' attitudes and knowledge about nonsuicidal self-injury among university students: A cross-national study.

Nonsuicidal self-injury (NSSI) is a commonly occurring, yet historically poorly understood, mental health concern among post-secondary students. The present study sought to identify the current knowledge needs of university stakeholders to inform training efforts around effective NSSI response and student support on university campuses.Participants were 1,762 university students, staff, and student-staff (77% female) from seven universities in Canada, the USA, New Zealand, and Australia.Participants completed an online survey about their attitudes and knowledge of both general mental health and NSSI.University stakeholders reported significantly greater stigma toward NSSI than mental illness in general. Student-staff reported greater perceived knowledge and comfort, and demonstrated greater knowledge of NSSI, than students and staff.Findings underscore the need for additional training and resources to reduce stigma and increase knowledge about NSSI on university campuses internationally.

Validation and Clinical Applicability of Whole-Volume Automated Segmentation of Optical Coherence Tomography in Retinal Disease Using Deep Learning.

IMPORTANCE: Quantitative volumetric measures of retinal disease in optical coherence tomography (OCT) scans are infeasible to perform owing to the time required for manual grading. Expert-level deep learning systems for automatic OCT segmentation have recently been developed. However, the potential clinical applicability of these systems is largely unknown. OBJECTIVE: To evaluate a deep learning model for whole-volume segmentation of 4 clinically important pathological features and assess clinical applicability. DESIGN, SETTING, PARTICIPANTS: This diagnostic study used OCT data from 173 patients with a total of 15 558 B-scans, treated at Moorfields Eye Hospital. The data set included 2 common OCT devices and 2 macular conditions: wet age-related macular degeneration (107 scans) and diabetic macular edema (66 scans), covering the full range of severity, and from 3 points during treatment. Two expert graders performed pixel-level segmentations of intraretinal fluid, subretinal fluid, subretinal hyperreflective material, and pigment epithelial detachment, including all B-scans in each OCT volume, taking as long as 50 hours per scan. Quantitative evaluation of whole-volume model segmentations was performed. Qualitative evaluation of clinical applicability by 3 retinal experts was also conducted. Data were collected from June 1, 2012, to January 31, 2017, for set 1 and from January 1 to December 31, 2017, for set 2; graded between November 2018 and January 2020; and analyzed from February 2020 to November 2020. MAIN OUTCOMES AND MEASURES: Rating and stack ranking for clinical applicability by retinal specialists, model-grader agreement for voxelwise segmentations, and total volume evaluated using Dice similarity coefficients, Bland-Altman plots, and intraclass correlation coefficients. RESULTS: Among the 173 patients included in the analysis (92 [53%] women), qualitative assessment found that automated whole-volume segmentation ranked better than or comparable to at least 1 expert grader in 127 scans (73%; 95% CI, 66%-79%). A neutral or positive rating was given to 135 model segmentations (78%; 95% CI, 71%-84%) and 309 expert gradings (2 per scan) (89%; 95% CI, 86%-92%). The model was rated neutrally or positively in 86% to 92% of diabetic macular edema scans and 53% to 87% of age-related macular degeneration scans. Intraclass correlations ranged from 0.33 (95% CI, 0.08-0.96) to 0.96 (95% CI, 0.90-0.99). Dice similarity coefficients ranged from 0.43 (95% CI, 0.29-0.66) to 0.78 (95% CI, 0.57-0.85). CONCLUSIONS AND RELEVANCE: This deep learning-based segmentation tool provided clinically useful measures of retinal disease that would otherwise be infeasible to obtain. Qualitative evaluation was additionally important to reveal clinical applicability for both care management and research.

To meat, or not to meat: A longitudinal investigation of transitioning to and from plant-based diets.

Concerns over potential negative effects of excessive meat consumption on both the environment and personal health, coupled with long-standing debates over animal rights, have motivated research on the prevalence and predictors of plant-based versus meat-based diets. Yet few studies have examined longitudinal trends in dietary behaviours using large national samples. We address this gap by examining the prevalence, predictors, and annual change in the self-reported dietary behaviour of a large national probability sample of New Zealand adults (categorised as omnivore, vegetarian, or vegan; Ns = 12,259-50,964). Consistent with our pre-registered hypotheses, omnivore was the most prevalent dietary category (94.1%). Moreover, higher levels of conservative ideologies (i.e., political conservatism, Right-Wing Authoritarianism, and Social Dominance Orientation), lower subjective health, lower environmental efficacy, and lower disgust sensitivity predicted having an omnivore (vs. vegetarian or vegan) diet. Longitudinal analyses further revealed that the probability of shifting from an omnivore diet to a vegetarian or vegan diet over a one-year period was low, and that veganism was the least stable dietary category. Both gender (men) and political conservatism predicted lower probabilities of transitioning from meat to no-meat diets over time.

Nonsuicidal self-injury thoughts and behavioural characteristics: Associations with suicidal thoughts and behaviours among community adolescents.

BACKGROUND: We consider whether nonsuicidal self-injury (NSSI) thoughts - in the absence of any NSSI behaviour - are associated with suicidal thoughts and behaviours among adolescents, before examining whether characteristics of NSSI behaviour are associated with greater suicidal thoughts and behaviours. METHODS: Adolescents (n = 2,057, M age =15.56) recruited from secondary schools reported their lifetime history of NSSI, suicidal thoughts and behaviours, NSSI characteristics, and NSSI functions. Receiver Operating Characteristic analysis test whether NSSI status and characteristics of NSSI behaviour are diagnostic of clinically elevated suicidal thoughts and behaviours (a score of 7 or higher on the Suicide Behaviours Questionnaire-Revised). Regression models test whether NSSI functions predict greater suicidality. RESULTS: Adolescents with NSSI thoughts and those with NSSI behaviour were more likely to report lifetime suicidal ideation and past-year suicide plan(s) than adolescents with no history of NSSI. In addition, adolescents with a history of NSSI were more likely to report a lifetime history of suicide attempt(s) as well as past-year suicide attempt(s) than adolescents with no history of NSSI. A greater number of NSSI methods, requiring medical assistance for NSSI injuries, and engaging in NSSI for self-punishment, anti-suicide, and sensation-seeking functions were associated with greater severity of suicidal thoughts and behaviours. LIMITATIONS: Data are cross-sectional, limiting inferences about causality. CONCLUSIONS: Findings emphasize the importance of NSSI thoughts and characteristics of NSSI behaviour in understanding the complex relationship between NSSI and suicidal thoughts and behaviours among adolescents.

CHD2-Related CNS Pathologies.

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators. These mutations in the CHD2 gene are causative of early onset epileptic encephalopathy, abnormal brain function, and intellectual disability. Our understanding of the mechanisms by which modification or loss of CHD2 cause this condition remains poorly understood. Here, we review what is known and still to be elucidated as regards the structure and function of CHD2 and how its dysregulation leads to a highly variable range of phenotypic presentations.

Quantitative Analysis of OCT for Neovascular Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: To apply a deep learning algorithm for automated, objective, and comprehensive quantification of OCT scans to a large real-world dataset of eyes with neovascular age-related macular degeneration (AMD) and make the raw segmentation output data openly available for further research. DESIGN: Retrospective analysis of OCT images from the Moorfields Eye Hospital AMD Database. PARTICIPANTS: A total of 2473 first-treated eyes and 493 second-treated eyes that commenced therapy for neovascular AMD between June 2012 and June 2017. METHODS: A deep learning algorithm was used to segment all baseline OCT scans. Volumes were calculated for segmented features such as neurosensory retina (NSR), drusen, intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), retinal pigment epithelium (RPE), hyperreflective foci (HRF), fibrovascular pigment epithelium detachment (fvPED), and serous PED (sPED). Analyses included comparisons between first- and second-treated eyes by visual acuity (VA) and race/ethnicity and correlations between volumes. MAIN OUTCOME MEASURES: Volumes of segmented features (mm3) and central subfield thickness (CST) (µm). RESULTS: In first-treated eyes, the majority had both IRF and SRF (54.7%). First-treated eyes had greater volumes for all segmented tissues, with the exception of drusen, which was greater in second-treated eyes. In first-treated eyes, older age was associated with lower volumes for RPE, SRF, NSR, and sPED; in second-treated eyes, older age was associated with lower volumes of NSR, RPE, sPED, fvPED, and SRF. Eyes from Black individuals had higher SRF, RPE, and serous PED volumes compared with other ethnic groups. Greater volumes of the majority of features were associated with worse VA. CONCLUSIONS: We report the results of large-scale automated quantification of a novel range of baseline features in neovascular AMD. Major differences between first- and second-treated eyes, with increasing age, and between ethnicities are highlighted. In the coming years, enhanced, automated OCT segmentation may assist personalization of real-world care and the detection of novel structure-function correlations. These data will be made publicly available for replication and future investigation by the AMD research community.

Effects of the COVID-19 pandemic and nationwide lockdown on trust, attitudes toward government, and well-being.

The contagiousness and deadliness of COVID-19 have necessitated drastic social management to halt transmission. The immediate effects of a nationwide lockdown were investigated by comparing matched samples of New Zealanders assessed before (Nprelockdown = 1,003) and during the first 18 days of lockdown (Nlockdown = 1,003). Two categories of outcomes were examined: (a) institutional trust and attitudes toward the nation and government and (b) health and well-being. Applying propensity score matching to approximate the conditions of a randomized controlled experiment, the study found that people in the pandemic/lockdown group reported higher trust in science, politicians, and police, higher levels of patriotism, and higher rates of mental distress compared to people in the prelockdown prepandemic group. Results were confirmed in within-subjects analyses. The study highlights social connectedness, resilience, and vulnerability in the face of adversity and has applied implications for how countries face this global challenge. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Open to interpretation? Inconsistent reporting of lifetime nonsuicidal self-injury across two common assessments.

Nonsuicidal self-injury (NSSI) is typically assessed using either single-item questionnaires or checklists of common behaviors, but preliminary research suggests that checklists produce higher lifetime prevalence rates. In 2 preregistered studies (combined n = 1,364), we tested whether memory cueing afforded by behavioral checklists accounts for this discrepancy. Participants reported their lifetime NSSI history using both a single-item and a checklist, with presentation order randomized across participants. Nearly a third of participants reported inconsistent NSSI histories on the 2 assessments, with participants 1.57 times more likely to report an NSSI history on a checklist than on a single-item. Counter to the memory account, this discrepancy was evident even when participants completed the checklist first, suggesting that the increased prevalence estimates captured by checklists are unlikely to simply reflect memory facilitation. Across the 2 samples, 12.5% of participants would have been incorrectly screened out in 2-step assessments; these participants were more likely to have engaged in NSSI historically, less likely to self-injure by cutting, and (in Study 2 only) were more likely to be men. These studies suggest that the inconsistencies across 2 of the most common NSSI assessments arise because people dissimilar to the lay conceptualization of self-injury are less likely to endorse a single-item, even when they have affirmed engaging in self-injury behaviors on a checklist. We argue that single-item and checklist assessments capture different aspects of NSSI, such that future research should distinguish between behaviorally identified NSSI assessed with behavioral checklists and self-identified NSSI assessed with single-item assessments. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Predicting conversion to wet age-related macular degeneration using deep learning.

Progression to exudative 'wet' age-related macular degeneration (exAMD) is a major cause of visual deterioration. In patients diagnosed with exAMD in one eye, we introduce an artificial intelligence (AI) system to predict progression to exAMD in the second eye. By combining models based on three-dimensional (3D) optical coherence tomography images and corresponding automatic tissue maps, our system predicts conversion to exAMD within a clinically actionable 6-month time window, achieving a per-volumetric-scan sensitivity of 80% at 55% specificity, and 34% sensitivity at 90% specificity. This level of performance corresponds to true positives in 78% and 41% of individual eyes, and false positives in 56% and 17% of individual eyes at the high sensitivity and high specificity points, respectively. Moreover, we show that automatic tissue segmentation can identify anatomical changes before conversion and high-risk subgroups. This AI system overcomes substantial interobserver variability in expert predictions, performing better than five out of six experts, and demonstrates the potential of using AI to predict disease progression.

A Fresh Start or the Devil You Know? Examining Relationships Between Release Location Choices, Community Experiences, and Recidivism for High-Risk Parolees.

This study investigated the effects of residential relocation in a sample of 282 high-risk male offenders paroled from New Zealand prisons. Initially we compared those returning to their old neighborhoods (devil you know) and those released to a new location (fresh start). This second category was then further divided: those released to a new location voluntarily (fresh start-voluntary) versus those forced to start anew at the behest of the parole board that was releasing them (fresh start-duress). All three categories were then compared on the quality of their community experiences and recidivism. Results indicated that parolees returning by choice to either their old neighborhood or a new location each were reconvicted in the first year after release at approximately the same rate; however, parolees relocating to a new area at the direction of the parole board (under duress) were reconvicted at a higher rate than those in either of the voluntary location categories. Significant group differences in ratings of community life quality were few, but there were some indications that compared with those choosing to return to a familiar location, making a voluntary residential relocation may lead to better parole experiences, particularly in terms of avoiding criminal peers, and that making a residential relocation under duress may lead to poorer parole experiences than for those returning to a familiar location.

Coding Responses to an Open-ended Gender Measure in a New Zealand National Sample.

In light of the methodological and ethical issues associated with using a male/female tick box to collect gender data, researchers are increasingly questioning how to measure gender inclusively in survey research. Open-ended measures afford the greatest flexibility, though whether they are practical for large-scale surveys has yet to be tested. Here, we systematically assess the feasibility of open-ended gender measures drawing on a New Zealand national probability sample (New Zealand Attitudes and Values Study, N = 15,758). We asked participants "What is your gender?" as an open-ended measure of gender, and developed a simple, cost-effective coding scheme for coding qualitative gender data. Results indicate that very few participants (n = 15) self-identified as transgender, or outside of the male/female gender binary. Moreover, we find no evidence that implementation of the open-ended measure contributes to non-response rates or panel attrition. Taken together, these results demonstrate that large-scale surveys can feasibly implement inclusive measures of gender as an alternative to binary categorical measures. Because the single-measure approach likely underestimates the number of transgender participants, however, researchers interested in identifying all participants whose gender differs from their assigned sex should utilize two-step methods, which assess gender as well as assigned sex at birth.

The influence of social dominance orientation and right-wing authoritarianism on environmentalism: A five-year cross-lagged analysis.

Social dominance orientation (SDO) and right-wing authoritarianism (RWA) are ideological attitudes that predict lower concern for the environment and less willingness to act on climate change. Research generally shows that SDO and RWA exhibit moderate, negative relationships with environmentalism. We examine the longitudinal influence of SDO and RWA on people's willingness to change their behaviour to benefit the environment in a national probability sample over five years. We show that both ideological attitudes relate to lower environmentalism across time and that the SDO effect was stronger than the RWA effect, yet the association from environmentalism to later endorsement of SDO is stronger than the reverse. Interestingly, these findings suggest that the more likely temporal association flows from environmentalism to SDO.

Prefrontal brain lesions reveal magical ideation arises from enhanced religious experiences.

Magical ideation refers to beliefs about causality that lack empirical bases. Few studies have investigated the neural correlates of magical thinking and religious beliefs. Here, we investigate the association between magical ideation and religious experience in a sample of Vietnam veterans who sustained penetrating traumatic brain injury (pTBI) and matched healthy controls (HCs). Scores on the Magical Ideation Scale were positively correlated with scores on the Religious Experience Scale, but only in pTBI patients. Lesion mapping analyses in subgroups of pTBI patients indicated that prefrontal cortex (PFC) lesions were associated with increased magical ideation scores and this relationship was mediated by religious experience. Our findings clarify the mechanism by which the frontal lobe processes modulate magical beliefs. Suppression of the PFC opens people to religious experiences, which in turn increases magical ideation.

Changes in perceived scientific consensus shift beliefs about climate change and GM food safety.

Despite an overwhelming scientific consensus, a sizable minority of people doubt that human activity is causing climate change. Communicating the existence of a scientific consensus has been suggested as a way to correct individuals' misperceptions about human-caused climate change and other scientific issues, though empirical support is mixed. We report an experiment in which psychology students were presented with consensus information about two issues, and subsequently reported their perception of the level of consensus and extent of their endorsement of those issues. We find that messages about scientific consensus on the reality of anthropogenic climate change and the safety of genetically modified food shift perceptions of scientific consensus. Using mediation models we also show that, for both these issues, high consensus messages also increase reported personal agreement with the scientific consensus, mediated by changes in perceptions of a scientific consensus. This confirms the role of perceived consensus in informing personal beliefs about climate change, though results indicate the impact of single, one-off messages may be limited.