Biological and psychological predictors of cognitive function in breast cancer patients before surgery.

PURPOSE: Research suggests that cancer-related cognitive impairment (CRCI) can occur before breast cancer (BC) treatment. The limited extant evidence suggests the underlying mechanisms could be stress-related. Potential psychological and biological predictors of CRCI prior to any BC treatment were examined. METHODS: 112 treatment-naïve women with BC and 67 healthy controls (HC) completed a neuropsychological test battery to assess cognitive impairment and a self-report battery to assess cognitive complaints, cancer-related stress, depressive and anxiety symptoms. Morning and evening cortisol and α-amylase were collected from saliva. Multilinear regressions were conducted. RESULTS: Treatment-naïve BC patients were more frequently impaired in verbal memory and processing speed and reported more cognitive complaints (all p < .001) than HC. BC patients and HC did not differ in overall cognitive impairment (p = .21). Steeper α-amylase, lower cancer-related stress and younger age was associated with better overall cognitive function in treatment-naïve BC patients. Higher depressive symptoms predicted higher levels of cognitive complaints in BC patients. CONCLUSION: Overall, these findings suggest that stress plays a role in CRCI. This study is the first to associate α-amylase with cognitive function in cancer patients, informing future research. The findings on impairment in processing speed and verbal memory among treatment-naïve BC highlight the need to screen for such impairments among BC patients and indicate that future studies on CRCI should include baseline assessments prior to BC treatment. If replicated, these findings could inform the development and testing of appropriate interventions to decrease CRCI among cancer patients. CLINICAL TRIALS REGISTRATION NUMBER: NCT04418856, date of registration: 06.05.2020.

Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex.

Identification and characterisation of novel targets for treatment is a priority in the field of psychiatry. FKBP5 is a gene with decades of evidence suggesting its pathogenic role in a subset of psychiatric patients, with potential to be leveraged as a therapeutic target for these individuals. While it is widely reported that FKBP5/FKBP51 mRNA/protein (FKBP5/1) expression is impacted by psychiatric disease state, risk genotype and age, it is not known in which cell types and sub-anatomical areas of the human brain this occurs. This knowledge is critical to propel FKBP5/1-targeted treatment development. Here, we performed an extensive, large-scale postmortem study (n = 1024) of FKBP5/1, examining neocortical areas (BA9, BA11 and ventral BA24/BA24a) derived from subjects that lived with schizophrenia, major depression or bipolar disorder. With an extensive battery of RNA (bulk RNA sequencing, single-nucleus RNA sequencing, microarray, qPCR, RNAscope) and protein (immunoblot, immunohistochemistry) analysis approaches, we thoroughly investigated the effects of disease state, ageing and genotype on cortical FKBP5/1 expression including in a cell type-specific manner. We identified consistently heightened FKBP5/1 levels in psychopathology and with age, but not genotype, with these effects strongest in schizophrenia. Using single-nucleus RNA sequencing (snRNAseq; BA9 and BA11) and targeted histology (BA9, BA24a), we established that these disease and ageing effects on FKBP5/1 expression were most pronounced in excitatory superficial layer neurons of the neocortex, and this effect appeared to be consistent in both the granular and agranular areas examined. We then found that this increase in FKBP5 levels may impact on synaptic plasticity, as FKBP5 gex levels strongly and inversely correlated with dendritic mushroom spine density and brain-derived neurotrophic factor (BDNF) levels in superficial layer neurons in BA11. These findings pinpoint a novel cellular and molecular mechanism that has potential to open a new avenue of FKBP51 drug development to treat cognitive symptoms in psychiatric disorders.

Biological embedding of experience: A primer on epigenetics.

Biological embedding occurs when life experience alters biological processes to affect later life health and well-being. Although extensive correlative data exist supporting the notion that epigenetic mechanisms such as DNA methylation underlie biological embedding, causal data are lacking. We describe specific epigenetic mechanisms and their potential roles in the biological embedding of experience. We also consider the nuanced relationships between the genome, the epigenome, and gene expression. Our ability to connect biological embedding to the epigenetic landscape in its complexity is challenging and complicated by the influence of multiple factors. These include cell type, age, the timing of experience, sex, and DNA sequence. Recent advances in molecular profiling and epigenome editing, combined with the use of comparative animal and human longitudinal studies, should enable this field to transition from correlative to causal analyses.

Association between adverse childhood experiences and premenstrual disorders: a cross-sectional analysis of 11,973 women.

BACKGROUND: Childhood abuse and neglect have been associated with premenstrual disorders (PMDs), including premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). However, the associations of other adverse childhood experiences (ACEs) and the cumulative number of ACEs with PMDs remain to be explored. METHODS: To evaluate the associations of the cumulative number and types of ACEs with PMDs, we conducted a cross-sectional analysis with a subsample of menstruating women within the Stress-And-Gene-Analysis (SAGA) cohort, assessed for PMDs and ACEs (N=11,973). The cumulative and individual exposure of 13 types of ACEs was evaluated by a modified ACE-International Questionnaire. A modified version of the Premenstrual Symptom Screening Tool was used to identify probable cases of PMDs, further sub-grouped into PMS and PMDD. Prevalence ratios (PRs) of PMDs in relation to varying ACEs were estimated using Poisson regression. RESULTS: At a mean age of 34.0 years (standard deviation (SD) 9.1), 3235 (27%) met the criteria of probable PMDs, including 2501 (21%) for PMS and 734 (6%) for PMDD. The number of ACEs was linearly associated with PMDs (fully-adjusted PR 1.12 per ACE, 95% CI 1.11-1.13). Specifically, the PR for PMDs was 2.46 (95% CI 2.21-2.74) for women with 4 or more ACEs compared with women with no ACEs. A stronger association was observed for probable PMDD compared to PMS (p for difference <0.001). The associations between ACEs and PMDs were stronger among women without PTSD, anxiety, or depression, and without childhood deprivation and were stronger among women a lower level of social support (p for interaction<0.001). All types of ACEs were positively associated with PMDs (PRs ranged from 1.11 to 1.51); the associations of sexual abuse, emotional neglect, family violence, mental illness of a household member, and peer and collective violence were independent of other ACEs. CONCLUSIONS: Our findings suggest that childhood adverse experiences are associated with PMDs in a dose-dependent manner. If confirmed by prospective data, our findings support the importance of early intervention for girls exposed to ACEs to minimize risks of PMDs and other morbidities in adulthood.

Substance Use Among Youth During the COVID-19 Pandemic: a Systematic Review.

PURPOSE OF REVIEW: To review the literature on the trends in substance use among youth during the coronavirus SARS-CoV-2 (COVID-19) pandemic. RECENT FINDINGS: The pandemic has given rise to concerns about the mental health and social well-being of youth, including its potential to increase or exacerbate substance use behaviors. This systematic review identified and included 49 studies of use across alcohol, cannabis, tobacco, e-cigarettes/vaping, and other drugs, and unspecified substances. The majority of studies across all categories of youth substance use reported reductions in prevalence, except in the case of other drugs and unspecified drug and substance use, which included three studies that reported an increase in use and three studies that reported decrease in use. Overall, the results of this review suggest that the prevalence of youth substance use has largely declined during the pandemic. Youth substance use in the post-pandemic years will require monitoring and continued surveillance.

A multi-level developmental approach towards understanding adolescent mental health and behaviour: rationale, design and methods of the LIFECOURSE study in Iceland.

PURPOSE: Identifying and understanding modifiable risk and protective factors that can inform early detection and intervention to prevent adolescent emotional problems and harmful behaviours is among the most pressing modern-day public health challenges. This paper describes the rationale, objectives, methods, and anticipated outcomes of the LIFECOURSE study, a multi-level, bio-psychosocial prospective study designed to advance our understanding of factors that shape adolescent mental health and behaviour. METHODS: Conducted by the Icelandic Centre for Social Research and Analysis at Reykjavik University, LIFECOURSE is a longitudinal population-based developmental study of Icelandic adolescents born in 2004. The study utilizes a comprehensive multi-informant assessment of individual, societal and biological factors measured across the lifespan. Data assembly and collection were conducted from 2016-2020 and utilize both retrospective and prospective data sources: (a) retrospective registry data assembled from seven national databases, (b) prospectively collected social surveys and (c) biomarker samples. RESULTS: Of the 3914 eligible adolescents, 60.8% (n = 2378) provided informed parental consent and student assent to participate in the study, with approximately half of the participants being female (n = 1175, 49.4%) and the majority being born in the capital area (n = 1455; 61.2%). The coverage of available data from the national databases and participation in the social surveys ranged from 81.7 to 100%. CONCLUSIONS: Major gaps remain in our knowledge of how individual, societal and biological factors across the lifespan-from early life to adolescence-interact and shape the risk for emotional problems and harmful behaviours during adolescence. The LIFECOURSE study was designed to address this knowledge gap.

Gene × Environment Interactions: From Molecular Mechanisms to Behavior.

Gene-by-environment interactions (G×Es) can provide important biological insights into psychiatric disorders and may consequently have direct clinical implications. In this review, we begin with an overview of the major challenges G×E studies have faced (e.g., difficulties replicating findings and high false discovery rates). In light of these challenges, this review focuses on describing examples in which we might begin to understand G×Es on the molecular, cellular, circuit, and behavioral level and link this interaction to altered risk for the development of psychiatric disorders. We also describe recent studies that utilize a polygenic approach to examine G×Es. Finally, we discuss how gaining a deeper understanding of G×Es may translate into a therapeutic practice with more targeted treatments.

Parent Management Training and Collaborative & Proactive Solutions: A Randomized Control Trial for Oppositional Youth.

This study examined the efficacy of Collaborative & Proactive Solutions (CPS) in treating oppositional defiant disorder (ODD) in youth by comparing this novel treatment to Parent Management Training (PMT), a well-established treatment, and a waitlist control (WLC) group. One hundred thirty-four youth (ages 7-14, 61.9% male, 83.6% White) who fulfilled Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for ODD were randomized to CPS, PMT, or WLC groups. ODD was assessed with semistructured diagnostic interviews, clinical global severity and improvement ratings, and parent report measures. Assessments were completed pretreatment, posttreatment, and at 6 months following treatment. Responder and remitter analyses were undertaken using intent-to-treat mixed-models analyses. Chronological age, gender, and socioeconomic status as well as the presence of comorbid attention deficit/hyperactivity and anxiety disorders were examined as predictors of treatment outcome. Both treatment conditions were superior to the WLC condition but did not differ from one another in either our responder or remitter analyses. Approximately 50% of youth in both active treatments were diagnosis free and were judged to be much or very much improved at posttreatment, compared to 0% in the waitlist condition. Younger age and presence of an anxiety disorder predicted better treatment outcomes for both PMT and CPS. Treatment gains were maintained at 6-month follow-up. CPS proved to be equivalent to PMT and can be considered an evidence-based, alternative treatment for youth with ODD and their families.

Treatment Outcomes in Anxious Youth with and without Comorbid ADHD in the CAMS.

The purpose of this study is to examine the influence of Attention-Deficit/Hyperactivity Disorder (ADHD), independent of Oppositional Defiant Disorder (ODD), on acute treatment response, remission rates and maintenance of gains at 6-month follow-up in anxious youth (ages 7-17, 76% Caucasian, 52% female) who received cognitive-behavioral therapy (CBT) alone, pharmacotherapy alone, the combination of CBT and pharmacotherapy or placebo pill in the Child/Adolescent Multimodal Study. Treatment response was defined as independent evaluator rated meaningful improvement in anxiety. Remission was operationalized as the absence of targeted anxiety disorders. ADHD and ODD were examined as moderators of outcomes at a diagnostic level. In the CBT group only, an ADHD diagnosis predicted poorer immediate treatment response and remission rates. However, these associations were not obtained for the pharmacotherapy groups. Participants with comorbid ODD were not less likely to achieve acute treatment response and remission rates than their counterparts across treatment conditions. Due to small sample size of the comorbid subgroups, our analyses must be considered preliminary. Nevertheless, our initial findings suggest further exploration of the separate roles of ADHD and ODD are worth pursuing, as they may be differentially associated with treatment outcomes in anxious youth treated with CBT but not youth treated with pharmacotherapy. If confirmed, findings may indicate that anxious youth with comorbid ADHD are less likely to benefit from CBT strategies alone and raise the possibility that these youth need adjunctive pharmacotherapy or psychosocial interventions.

Sexual violence in the workplace and associated health outcomes: a nationwide, cross-sectional analysis of women in Iceland.

BACKGROUND: Workplace sexual violence against women is a pressing global issue with scarce knowledge on its health implications. Existing research is largely limited to specific occupations, which calls for comprehensive, population-based studies. This study aimed to examine the associations between self-labelled workplace sexual violence and a variety of health outcomes in a nationally representative sample of Icelandic women aged 18-69 years. METHODS: Participants in this cross-sectional study were women in the Stress-And-Gene-Analysis (SAGA) cohort who answered the question regarding workplace sexual violence, defined in our study as encompassing all work sectors, academic settings, and other school environments. Eligible participants were women, aged 18-69 years, residing in Iceland, who spoke Icelandic and were listed in the Icelandic Population Register or had a contact number registered with the online 1819 service. Poisson and binomial regressions were used to assess the associations between workplace sexual violence and validated measures of current mental and physical health outcomes (eg, probable depression, general anxiety, and severe sleep problems). Multiple imputation was performed to account for missing values in the dataset. FINDINGS: The study was conducted from March 1, 2018, to July 1, 2019. Of the 113 814 women deemed eligible for study inclusion, 104 197 were invited to take part in the online survey. Of those invited, 30 403 women completed the survey and were included in the SAGA cohort. Among these participants, 15 812 provided answers to the question regarding exposure to workplace sexual harassment or violence. Exposure to sexual violence was associated with an increased prevalence of probable depression (prevalence ratio [PR] 1·50 [95% CI 1·41-1·60]), general anxiety (PR 1·49 [1·40-1·59]), social phobia (PR 1·62 [1·48-1·78]), self-harm (PR 1·86 [1·53-2·28]), suicidal ideation (PR 1·68 [1·44-1·68]), suicide attempts (PR 1·99 [1·62-2·44]), binge drinking (PR 1·10 [1·01-1·20]), sleep problems (PR 1·41 [1·48-1·91]), physical symptoms (PR 1·59 [1·48-1·70]), and sick leave (PR 1·20 [1·12-1·28]). The prevalence of the health outcomes among those exposed show age-related differences: younger women report anxiety or depression more frequently, while older women report sleep problems after experiencing workplace sexual violence. INTERPRETATION: In this cross-sectional study self-reported experiences of sexual violence in the workplace were associated with several self-reported health outcomes. The findings suggest a need for targeted interventions to promote workplace safety and to mitigate adverse health implications among people who have experienced workplace sexual violence. Future research should explore factors such as the frequency, duration, and relationship dynamics of workplace sexual violence, as well as the effect on different genders and sexual orientations, to deepen our understanding of these experiences and inform effective prevention strategies. FUNDING: Reykjavík Energy Research Fund, The Icelandic Gender Equality Fund, European Research Council, and Icelandic Center for Research.

Adverse Childhood Experiences and Adult Mental Health Outcomes.

Importance: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders. Objective: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding. Design, Setting, and Participants: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023. Exposures: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey. Main Outcomes and Measures: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register. Results: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11). Conclusions and relevance: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

Co-Occurring Conduct Problems and Anxiety: Implications for the Functioning and Treatment of Youth with Oppositional Defiant Disorder.

Conduct problems and anxiety symptoms commonly co-occur among youths with oppositional defiant disorder (ODD); however, how these symptoms influence functioning and treatment outcomes remains unclear. This study examined subtypes based on these co-occurring symptoms in a clinical sample of 134 youths (Mage = 9.67, 36.6% female, 83.6% white) with ODD and the predictive power of these subgroups for youth functioning and psychosocial treatment outcomes. The latent profile analysis (LPA) was used to identify subgroups based on parent- and self-reported conduct problems and anxiety symptoms. Differences among the subgroups in clinician-, parent-, and/or self-reported accounts of symptom severity, school performance, underlying processing known to be impaired across ODD, conduct and anxiety disorders, self-concept, and psychosocial treatment outcomes were examined. Four distinct profiles were identified: (1) Low Anxiety/Moderate Conduct Problems (n = 42); (2) High Anxiety/Moderate Conduct Problems (n = 33); (3) Moderate Anxiety/Moderate Conduct Problems (n = 40); and (4) Moderate Anxiety/High Conduct Problems (n = 19). The Moderate Anxiety/High Conduct Problems group exhibited more severe behavioral problems, greater difficulties with negative emotionality, emotional self-control, and executive functioning; they also demonstrated worse long-term treatment outcomes than the other subgroups. These findings suggest more homogeneous subgroups within and across diagnostic categories may result in a deeper understanding of ODD and could inform nosological systems and intervention efforts.

Premenstrual disorders and gender differences in adolescent mental health.

BACKGROUND: Gender differences in mental health emerge in adolescence. The timing coincides with the development of premenstrual disorders (PMDs). Here, we examine the association between PMDs and adolescent mental health in the context of gender differences. METHODS: A cross-sectional analysis comprising 21,239[10,563 (49.7 %) girls] individuals aged 10-19 years from the Santai Youth Mental Health Promotion Cohort in China. Possible PMDs, major depression disorder (MDD), general anxiety disorder (GAD), history of self-injury, and high suicide-risk status were surveyed using standard questionnaires. We used logistic regression to contrast the prevalence of outcomes between girls with and without PMDs, and boys. RESULTS: The prevalence rates of possible MDD and GAD were comparable between girls without PMDs and boys [OR1.03 (0.96-1.11) and 0.99 (0.92-1.07)], whereas a higher burden was observed in girls with PMDs [OR4.76(4.31-5.26) and 3.86(3.50-4.27), respectively]. Moreover, MDD/GAD prevalence among premenarchal girls was comparable to their peer boys. Greater gender differences in self-injury and high suicide-risk status were also found for girls with PMDs [OR 4.70 (4.22-5.24) and 7.49 (6.6-8.5)] than that for girls without PMDs [OR1.45(1.33-1.59) and 1.81 (1.62-2.03)]. LIMITATION: Girls with PMDs may have overreported depressive and/or anxiety symptoms due to the overlap of symptomology. CONCLUSIONS: The greater gender differences in adolescent mental ill-health among girls with PMDs lend support to the hypothesis that PMDs play an important role in the gender disparities in adolescent mental health, particularly in depression and anxiety.

Community-Delivered Collaborative and Proactive Solutions and Parent Management Training for Oppositional Youth: A Randomized Trial.

The aim of this study was to examine the relative effectiveness of Collaborative and Proactive Solutions (CPS) and Parent Management Training (PMT) for youth with oppositional defiant disorder (ODD) in a community setting. Based on a semistructured diagnostic interview, 160 youth with ODD (ages 7-14; 72% male; ethnicity representative of the wider Australian population) were randomized to CPS (n = 81) or PMT (n = 79) for up to 16 weekly sessions. The primary hypothesis was that participants in the CPS group, treated in a community setting, would exhibit significant improvement in ODD, equivalent to that of an evidence-based treatment, PMT. Assessment was conducted at baseline, post-intervention, and at 6-month follow-up, using independently rated semistructured diagnostic interviews, parent ratings of ODD symptoms, and global ratings of severity and improvement. Analyses were conducted with hierarchical growth linear modeling, ANCOVA, and equivalence testing using an intent-to-treat sample. Both treatments demonstrated similar outcomes, with 45-50% of youth in the nonclinical range after treatment, and 67% considered much improved. No differences were found between groups, and group equivalency was shown on the independent clinician and parent-rated measures. Gains were maintained at the 6-month follow-up. In conclusion, CPS works as effectively as the well-established treatment, PMT, for youths with ODD, when implemented in a community-based setting. As such, CPS provides a viable choice for families who seek alternate treatments.

Effect of the COVID-19 pandemic on adolescent mental health and substance use up to March, 2022, in Iceland: a repeated, cross-sectional, population-based study.

BACKGROUND: Poor mental health in the first year of the COVID-19 pandemic has been well documented in adolescents; however, less is known about the longer-term effect of the pandemic. We aimed to examine adolescent mental health and substance use as well as covariates associated with these outcomes 1 year or more into the pandemic. METHODS: A nationwide sample of adolescents aged 13-18 years enrolled in school in Iceland were invited to complete surveys administered during October-November or February-March, 2018, October-November, 2020, February-March or October-November, 2021, and February-March 2022. The survey was in Icelandic for all administrations and offered to adolescents aged 13-15 years in English in 2020 and 2022 and in Polish in 2022. Surveys assessed depressive symptoms (Symptom Checklist-90); mental wellbeing (Short Warwick Edinburgh Mental Wellbeing Scale); and the frequency of cigarette smoking, e-cigarette use, and alcohol intoxication. Covariates comprised age, gender, and migration status as determined by language spoken at home, level of social restrictions based on residency, parental social support, and sleep duration (≥8 h nightly). Weighted mixed-effect models were used to determine the effect of time and the covariates on mental health and substance use. The main outcomes were assessed in all participants with more than 80% of the necessary data, and multiple imputation was used to handle missing data. Bonferroni corrections were used to adjust for multiple testing and analyses were considered significant at a p value of <0·0017. FINDINGS: 64 071 responses were submitted and analysed between 2018 and 2022. Elevated depressive symptoms and worsened mental wellbeing across girls and boys aged 13-18 years were observed to have been maintained up to 2 years into the pandemic (p>0·0017). Alcohol intoxication initially decreased during the pandemic but increased again as social restrictions eased (p<0·0001). No changes were observed in cigarette smoking and e-cigarette use during the COVID-19 pandemic. Higher levels of parental social support and an average sleep duration of 8 h or more per night were associated with mental health better outcomes and less substance use (p<0·0001). Social restrictions and migration background were inconsistently associated with the outcomes. INTERPRETATION: Population-level prevention targeting adolescent depressive symptoms should be prioritised in health policy in the wake of COVID-19. FUNDING: Icelandic Research Fund.

Risk factors for workplace sexual harassment and violence among a national cohort of women in Iceland: a cross-sectional study.

BACKGROUND: Sexual harassment and violence in the workplace are a serious public health concern for women worldwide with substantial costs due to sick leave and personnel turnover. Yet little is known about the prevalence of sexual harassment and violence at a population level, especially across work sectors. The aim of this study was to investigate the prevalence of workplace sexual harassment and violence by demographic factors and work sectors among Icelandic women. METHODS: For this cross-sectional study we analysed nationally representative, de-identified individual-level data from women who had responded to an online survey item about self-labelled current and lifetime workplace sexual harassment or violence as part of the Stress and Gene Analysis (SAGA) study, a cross-sectional nationally representative study done from March 1, 2018, to July 1, 2019. Eligible participants were women who resided in Iceland, were aged between 18 and 69 years, spoke Icelandic, and had a registered address from the Icelandic Population Register or a telephone number from the online 1819 service. We used binomial and Poisson regression analysis to study the cross-sectional association between workplace sexual harassment and violence and demographic factors (eg, age, sexual orientation, and education) and factors relating to the workplace (eg, work schedule), across works sectors. FINDINGS: Of 113 814 eligible women, 104 197 were invited to complete the online survey, of whom 30 403 women responded and were included in the SAGA cohort. 15 799 women answered the item about exposure to workplace sexual harassment or violence. 11 286 [71·4%] of 15 799 women answered the question about sexual orientation that were included in the survey from June, 2018. 5291 (33·5%) of 15 799 of participants reported having experienced workplace sexual harassment or violence during their lifetime, and 1178 (7·5%) in their current workplace. Such exposure in the current workplace was most common among women who were young (age 18-24 years: prevalence ratio [PR] 3·89 [95% CI 2·66-5·71]; age 25-34 years: 3·66 [2·53-5·31]), single (1·27 [1·12-1·43]), and worked shifts (2·32 [2·02-2·67]), with the highest prevalence rates observed among women in work sectors of public figures (15·67 [9·34-25·12]), tourism (15·01 [11·01-20·13]), and the legal system and security (13·56 [7·00-24·66]). Lifetime exposure to workplace sexual harassment or violence was more common among women who belonged to sexual minorities than among heterosexual women (PR 1·35 [1·24-1·46]). INTERPRETATION: Lifetime exposure to workplace sexual harassment or violence seems common among women in a Nordic welfare state. These findings provide nuanced targets for prevention and for public policies aimed at promoting women's safety in the work environment. FUNDING: Icelandic Gender Equality Fund, European Research Council, and Icelandic Centre for Research.

Adverse childhood experiences and resilience among adult women: A population-based study.

Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear. Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18-69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders. Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability (ß = -0.14; 95% CI-0.15,-0.13) and lower psychiatric resilience (ß = -0.28; 95% CI-0.29,-0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood. Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood. Funding: This work was supported by the European Research Council (Consolidator grant; UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051). HBD was supported by a doctoral grant from the University of Iceland Research Fund.

Using a Brief Mental Imagery Competing Task to Reduce the Number of Intrusive Memories: Exploratory Case Series With Trauma-Exposed Women.

BACKGROUND: Novel interventions should be developed for people who have undergone psychological trauma. In a previous case study, we found that the number of intrusive memories of trauma could be reduced with a novel intervention. The intervention included a brief memory reminder, a visuospatial task and mental rotation, and targeted trauma memory hotspots one at a time in separate sessions. OBJECTIVE: This case series (N=3) extended the first case study with 3 new cases to determine whether a similar pattern of beneficial results is observed. We explored whether the brief intervention would result in reduced numbers of intrusive memories and whether it would impact symptoms of posttraumatic stress, depression and anxiety, and general functioning. Acceptability of the intervention was also explored. METHODS: A total of 3 women completed the study: 2 with posttraumatic stress disorder and other comorbidities and 1 with subthreshold posttraumatic stress disorder. The primary outcome was the change in the number of intrusive memories from the baseline phase to the intervention phase and at the 1-month follow-up, with an assessment of the intrusion frequency at 3 months. Participants monitored the number of intrusive memories in a daily diary for 1 week at baseline, for maximum of 6 weeks during the intervention phase and for 1 week at the 1-month and 3-month follow-ups. The intervention was delivered in person or digitally, with guidance from a clinical psychologist. A repeated AB design was used (A was a preintervention baseline phase and B intervention phase). Intrusions were targeted individually, creating repetitions of an AB design. RESULTS: The total number of intrusive memories was reduced from the baseline to the intervention phase for all participants. The total number for participant 3 (P3) reduced from 38.8 per week during the baseline phase to 18.0 per week in the intervention phase. It was 13 at the 3-month follow-up. The total number for P4 reduced from 10.8 per week at baseline to 4.7 per week in the intervention phase. It was 0 at the 3-month follow-up. The total number for P5 was reduced from 33.7 at baseline to 20.7 per week in the intervention phase. It was 8 at the 3-month follow-up. All participants reported reduction in posttraumatic stress symptoms in the postintervention phase. Depression and anxiety symptoms reduced in 2 of the 3 participants in the postintervention phase. Acceptability was favorable. CONCLUSIONS: We observed good compliance with the intervention and intrusive memory diary in all 3 cases. The number of intrusive memories was reduced for all participants during the intervention phase and at the 1-month follow-up, with some improvement in other symptoms and functioning. Further research should explore the remote delivery of the intervention and whether nonspecialists can deliver the intervention effectively.

Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation.

Substantial sex differences have been reported in the physiological response to stress at multiple levels, including the release of the stress hormone, cortisol. Here, we explore the genomic variants in 93 females and 196 males regulating the initial transcriptional response to cortisol via glucocorticoid receptor (GR) activation. Gene expression levels in peripheral blood were obtained before and after GR-stimulation with the selective GR agonist dexamethasone to identify differential expression following GR-activation. Sex stratified analyses revealed that while the transcripts responsive to GR-stimulation were mostly overlapping between males and females, the quantitative trait loci (eQTLs) regulation differential transcription to GR-stimulation was distinct. Sex-stratified eQTL SNPs (eSNPs) were located in different functional genomic elements and sex-stratified transcripts were enriched within postmortem brain transcriptional profiles associated with Major Depressive Disorder (MDD) specifically in males and females in the cingulate cortex. Female eSNPs were enriched among SNPs linked to MDD in genome-wide association studies. Finally, transcriptional sensitive genetic profile scores derived from sex-stratified eSNPS regulating differential transcription to GR-stimulation were predictive of depression status and depressive symptoms in a sex-concordant manner in a child and adolescent cohort (n = 584). These results suggest the potential of eQTLs regulating differential transcription to GR-stimulation as biomarkers of sex-specific biological risk for stress-related psychiatric disorders.

Depressive symptoms, mental wellbeing, and substance use among adolescents before and during the COVID-19 pandemic in Iceland: a longitudinal, population-based study.

BACKGROUND: Adolescence represents a crucial developmental period in shaping mental health trajectories. In this study, we investigated the effect of the COVID-19 pandemic on mental health and substance use during this sensitive developmental stage. METHODS: In this longitudinal, population-based study, surveys were administered to a nationwide sample of 13-18-year-olds in Iceland in October or February in 2016 and 2018, and in October, 2020 (during the COVID-19 pandemic). The surveys assessed depressive symptoms with the Symptom Checklist-90, mental wellbeing with the Short Warwick Edinburgh Mental Wellbeing Scale, and the frequency of cigarette smoking, e-cigarette use, and alcohol intoxication. Demographic data were collected, which included language spoken at home although not ethnicity data. We used mixed effects models to study the effect of gender, age, and survey year on trends in mental health outcomes. FINDINGS: 59 701 survey responses were included; response rates ranged from 63% to 86%. An increase in depressive symptoms (ß 0·57, 95% CI 0·53 to 0·60) and worsened mental wellbeing (ß -0·46, 95% CI -0·49 to -0·42) were observed across all age groups during the pandemic compared with same-aged peers before COVID-19. These outcomes were significantly worse in adolescent girls compared with boys (ß 4·16, 95% CI 4·05 to 4·28, and ß -1·13, 95% CI -1·23 to -1·03, respectively). Cigarette smoking (OR 2·61, 95% CI 2·59 to 2·66), e-cigarette use (OR 2·61, 95% CI 2·59 to 2·64), and alcohol intoxication (OR 2·59, 95% CI 2·56 to 2·64) declined among 15-18-year-olds during COVID-19, with no similar gender differences. INTERPRETATION: Our results suggest that COVID-19 has significantly impaired adolescent mental health. However, the decrease observed in substance use during the pandemic might be an unintended benefit of isolation, and might serve as a protective factor against future substance use disorders and dependence. Population-level prevention efforts, especially for girls, are warranted. FUNDING: Icelandic Research Fund. TRANSLATION: For the Icelandic translation of the abstract see Supplementary Materials section.