Genome-wide association study meta-analysis of 9,619 cases with tic disorders.

BACKGROUND: Despite the significant personal and societal burden of tic disorders (TD), treatment outcomes remain modest, necessitating a deeper understanding of their etiology. Family history is the biggest known risk factor and identifying risk genes could accelerate progress in the field. METHODS: Expanding upon previous sample size limitations, we added 4,800 new TD cases and 971,560 controls, conducting a GWAS meta-analysis with 9,619 cases and 981,048 controls of European ancestry. We attempted to replicate the results in an independent deCODE Genetics GWAS (885 TD cases and 310,367 controls). To characterize GWAS findings, we conducted several post-GWAS gene-based and enrichment analyses. RESULTS: A genome-wide significant hit (rs79244681, p=2.27x10-08) within MCHR2-AS1 was identified, though it was not replicated. Post-GWAS analyses revealed a 13.8% SNP-heritability and three significant genes: BCL11B, NDFIP2, and RBM26. Common variant risk for TD was enriched within genes preferentially expressed in the cortico-striato-thalamo-cortical circuit (including the putamen, caudate, nucleus accumbens, and Brodman area 9) and five brain cell types (excitatory and inhibitory telencephalon-, inhibitory- di- and mesencephalon, hindbrain-, and medium spiny neurons). TD polygenic risk was enriched within loss-of-function intolerant genes (p=0.0017) and high-confidence neurodevelopmental disorder genes (p=0.0108). Of 112 genetic correlations, 43 were statistically significant, showing high positive correlations with most psychiatric disorders. Of the two SNPs previously associated with TD, one (rs2453763) replicated in an independent sub-sample of our GWAS (p=0.00018). CONCLUSIONS: This GWAS was still underpowered to identify high-confidence, replicable loci, but the results suggest imminent discovery of common genetic variants for TD.

Sleep well, worry less: A co-design study for the development of the SMILE app.

Objective: With the coronavirus disease 2019 pandemic exacerbating mental health concerns, the prevalence rates of anxiety and sleep problems have increased alarmingly among youth. Although 90% of patients with anxiety experience sleep problems, current interventions for anxiety often do not target sleep problems in youth. Given this lack, we designed the SMILE app, an intervention that addresses both anxiety and sleep problems simultaneously. Methods: As users' perspectives are essential to ensure app engagement and uptake, the features, designs, and functions of the SMILE app were evaluated using a participatory app design approach. Participants (N = 17) were youth aged 15 to 25 who reported co-morbid anxiety and sleep issues above clinical thresholds. After completing an online screening survey assessing demographics, anxiety, and sleep problems, participants shared app feedback through group-based, semi-structured co-design sessions. Qualitative analyses were conducted to identify common themes from participants' feedback. Results: While participants expressed enthusiasm for the SMILE app's features, particularly the Visualization, Journaling, and Psychoeducation features, and their variety, they criticized the design aspects of the app, such as the font and text amount. Most participants stated they would use the SMILE app or recommend it to a friend. Conclusion: By actively involving the target population in the design process, the SMILE app has the potential to notably improve the mental well-being of youth, though further research and development are required to realize this potential fully.

Smartphone-Delivered Attentional Bias Modification Training for Mental Health: Systematic Review and Meta-Analysis.

BACKGROUND: Smartphone-delivered attentional bias modification training (ABMT) intervention has gained popularity as a remote solution for alleviating symptoms of mental health problems. However, the existing literature presents mixed results indicating both significant and insignificant effects of smartphone-delivered interventions. OBJECTIVE: This systematic review and meta-analysis aims to assess the impact of smartphone-delivered ABMT on attentional bias and symptoms of mental health problems. Specifically, we examined different design approaches and methods of administration, focusing on common mental health issues, such as anxiety and depression, and design elements, including gamification and stimulus types. METHODS: Our search spanned from 2014 to 2023 and encompassed 4 major databases: MEDLINE, PsycINFO, PubMed, and Scopus. Study selection, data extraction, and critical appraisal were performed independently by 3 authors using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. When necessary, we pooled the standardized mean difference with a 95% CI. In addition, we conducted sensitivity, subgroup, and meta-regression analyses to explore moderator variables of active and placebo ABMT interventions on reducing symptoms of mental health problems and attentional bias. RESULTS: Our review included 12 papers, involving a total of 24,503 participants, and we were able to conduct a meta-analysis on 20 different study samples from 11 papers. Active ABMT exhibited an effect size (Hedges g) of -0.18 (P=.03) in reducing symptoms of mental health problems, while the overall effect remained significant. Similarly, placebo ABMT showed an effect size of -0.38 (P=.008) in reducing symptoms of mental health problems. In addition, active ABMT (Hedges g -0.17; P=.004) had significant effects on reducing attentional bias, while placebo ABMT did not significantly alter attentional bias (Hedges g -0.04; P=.66). CONCLUSIONS: Our understanding of smartphone-delivered ABMT's potential highlights the value of both active and placebo interventions in mental health care. The insights from the moderator analysis also showed that tailoring smartphone-delivered ABMT interventions to specific threat stimuli and considering exposure duration are crucial for optimizing their efficacy. This research underscores the need for personalized approaches in ABMT to effectively reduce attentional bias and symptoms of mental health problems. TRIAL REGISTRATION: PROSPERO CRD42023460749; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=460749.

Terror catastrophizing: association with anxiety, depression, and transgenerational effects.

Background & Objectives: Terror catastrophizing, defined as an ongoing fear of future terrorist attacks, is associated with a higher incidence of anxiety disorders, among other psychological impacts. However, previous studies examining terror catastrophizing's relationship to other mental health disorders are limited. The current study sought to determine if patients diagnosed with anxiety and depression would experience increased terror catastrophizing. Additionally, this study aimed to investigate whether parental terror catastrophizing increases children's internalizing symptoms.Design & Methods: Individuals were randomly drawn from the Danish Civil Registration System and invited to complete a series of questionnaires to measure terror catastrophizing tendency, lifetime parental trauma, and children's internalizing symptoms. In total, n = 4,175 invitees completed the survey of which 933 reported on a child between 6 and 18 years. Responses were analyzed using a generalized linear regression model.Results: Participants diagnosed with anxiety alone or comorbid with depression were more likely to experience symptoms of terror catastrophizing than undiagnosed participants (ß = 0.10, p < .001; ß = 0.07, p = .012). Furthermore, the parental tendency to catastrophize terror was associated with higher internalizing symptoms in children (ß = 0.09, p = .006), even after taking parental diagnoses, as well as lifetime and childhood trauma into account.Conclusion: The results can inform clinical practices to account for a patient's potential to exhibit increased terror catastrophizing tendencies or be more affected by traumatic events. Additionally, they can offer insights for designing novel preventative interventions for the whole family, due to the relation between parental tendencies for terror catastrophizing and the internalizing symptoms observed in children.

Diagnoses of comorbid anxiety and depression tend to have increased terror catastrophizing (TC); however, a sole anxiety diagnosis is associated with more TC, while sole depression is not.Informative for clinical practice to understand how patients with TC tendencies are more likely to be impacted by traumatic events.Parental TC symptoms are linked to internalizing symptoms in children; thus, this could inform the design of novel preventative interventions.

Extended Reality for Mental Health Evaluation: Scoping Review.

BACKGROUND: Mental health disorders are the leading cause of health-related problems worldwide. It is projected that mental health disorders will be the leading cause of morbidity among adults as the incidence rates of anxiety and depression grow worldwide. Recently, "extended reality" (XR), a general term covering virtual reality (VR), augmented reality (AR), and mixed reality (MR), is paving the way for the delivery of mental health care. OBJECTIVE: We aimed to investigate the adoption and implementation of XR technology used in interventions for mental disorders and to provide statistical analyses of the design, usage, and effectiveness of XR technology for mental health interventions with a worldwide demographic focus. METHODS: In this paper, we conducted a scoping review of the development and application of XR in the area of mental disorders. We performed a database search to identify relevant studies indexed in Google Scholar, PubMed, and the ACM Digital Library. A search period between August 2016 and December 2023 was defined to select papers related to the usage of VR, AR, and MR in a mental health context. The database search was performed with predefined queries, and a total of 831 papers were identified. Ten papers were identified through professional recommendation. Inclusion and exclusion criteria were designed and applied to ensure that only relevant studies were included in the literature review. RESULTS: We identified a total of 85 studies from 27 countries worldwide that used different types of VR, AR, and MR techniques for managing 14 types of mental disorders. By performing data analysis, we found that most of the studies focused on high-income countries, such as the United States (n=14, 16.47%) and Germany (n=12, 14.12%). None of the studies were for African countries. The majority of papers reported that XR techniques lead to a significant reduction in symptoms of anxiety or depression. The majority of studies were published in 2021 (n=26, 30.59%). This could indicate that mental disorder intervention received higher attention when COVID-19 emerged. Most studies (n=65, 76.47%) focused on a population in the age range of 18-65 years, while few studies (n=2, 3.35%) focused on teenagers (ie, subjects in the age range of 10-19 years). In addition, more studies were conducted experimentally (n=67, 78.82%) rather than by using analytical and modeling approaches (n=8, 9.41%). This shows that there is a rapid development of XR technology for mental health care. Furthermore, these studies showed that XR technology can effectively be used for evaluating mental disorders in a similar or better way that conventional approaches. CONCLUSIONS: In this scoping review, we studied the adoption and implementation of XR technology for mental disorder care. Our review shows that XR treatment yields high patient satisfaction, and follow-up assessments show significant improvement with large effect sizes. Moreover, the studies adopted unique designs that were set up to record and analyze the symptoms reported by their participants. This review may aid future research and development of various XR mechanisms for differentiated mental disorder procedures.

Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.

The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

Clinical implications of DNA methylation-based integrated classification of histologically defined grade 2 meningiomas.

The combination of DNA methylation analysis with histopathological and genetic features allows for a more accurate risk stratification and classification of meningiomas. Nevertheless, the implications of this classification for patients with grade 2 meningiomas, a particularly heterogeneous tumor entity, are only partially understood. We correlate the outcomes of histopathologically confirmed grade 2 meningioma with an integrated molecular-morphologic risk stratification and determine its clinical implications. Grade 2 meningioma patients treated at our institution were re-classified using an integrated risk stratification involving DNA methylation array-based data, copy number assessment and TERT promoter mutation analyses. Grade 2 meningioma cases according to the WHO 2021 criteria treated between 2007 and 2021 (n = 100) were retrospectively analyzed. The median clinical and radiographic follow-up periods were 59.8 and 54.4 months. A total of 38 recurrences and 17 deaths were observed. The local control rates of the entire cohort after 2-, 4-, and 6-years were 84.3%, 68.5%, and 50.8%, with a median local control time of 77.2 months. The distribution of the integrated risk groups were as follows: 31 low, 54 intermediate, and 15 high risk cases. In the multivariable Cox regression analysis, integrated risk groups were significantly associated with the risk of local recurrence (hazard ratio (HR) intermediate: 9.91, HR high-risk: 7.29, p < 0.01). Gross total resections decreased the risk of local tumor progression (HR gross total resection: 0.19, p < 0.01). The comparison of 1p status and integrated risk groups (low vs. intermediate/high) revealed nearly identical local control rates within their respective subgroups. In summary, only around 50% of WHO 2021 grade 2 meningiomas have an intermediate risk profile. Integrated molecular risk stratification is crucial to guide the management of patients with grade 2 tumors and should be routinely applied to avoid over- and undertreatment, especially concerning the use of adjuvant radiotherapy.

The mental health and traumatic experiences of mothers of children with 22q11DS.

Background: 22q11 Deletion Syndrome (22q11DS) is the most common microdeletion syndrome with broad phenotypic variability, leading to significant morbidity and some mortality. The varied health problems associated with 22q11DS and the evolving phenotype (both medical and developmental/behavioural) across the lifespan can strongly impact the mental health of patients as well as their caregivers. Like caregivers of children with other chronic diseases, caregivers of children with 22q11DS may experience an increased risk of traumatisation and mental health symptoms.Objective: The study's primary objective was to assess the frequency of traumatic experiences and mental health symptoms among mothers of children with 22q11DS. The secondary objective was to compare their traumatic experiences to those of mothers of children with other neurodevelopmental disorders (NDDs).Method: A total of 71 mothers of children diagnosed with 22q11DS completed an online survey about their mental health symptoms and traumatic experiences. Descriptive statistics were used to summarise the prevalence of their mental health symptoms and traumatic experiences. Logistic regression models were run to compare the traumatic experiences of mothers of children with 22q11DS to those of 335 mothers of children with other neurodevelopmental disorders (NDDs).Results: Many mothers of children with 22q11DS experienced clinically significant mental health symptoms, including depression (39%), anxiety (25%), and post-traumatic stress disorder (PTSD) symptoms (30%). The types of traumatic events experienced by mothers of children with 22q11DS differed from those of mothers of children with other NDDs as they were more likely to observe their child undergoing a medical procedure, a life-threatening surgery, or have been with their child in the intensive care unit.Conclusion: 22q11DS caregivers are likely to require mental health support and trauma-informed care, tailored to the specific needs of this population as they experience different kinds of traumatic events compared to caregivers of children with other NDDS.

Mothers of children with 22q11DS experience clinically significant levels of depression, anxiety, and PTSD.Mothers of children with 22q11DS experience many and diverse trauma particularly related to medical interventions of their child.The types of traumatic events experienced by mothers of children with 22q11DS are different from those of the mothers of children with other neurodevelopmental disorders.

Genome-Wide Association Study of Obsessive-Compulsive Symptoms including 33,943 individuals from the general population.

While 1-2% of individuals meet the criteria for a clinical diagnosis of obsessive-compulsive disorder (OCD), many more (~13-38%) experience subclinical obsessive-compulsive symptoms (OCS) during their life. To characterize the genetic underpinnings of OCS and its genetic relationship to OCD, we conducted the largest genome-wide association study (GWAS) meta-analysis of parent- or self-reported OCS to date (N = 33,943 with complete phenotypic and genome-wide data), combining the results from seven large-scale population-based cohorts from Sweden, the Netherlands, England, and Canada (including six twin cohorts and one cohort of unrelated individuals). We found no genome-wide significant associations at the single-nucleotide polymorphism (SNP) or gene-level, but a polygenic risk score (PRS) based on the OCD GWAS previously published by the Psychiatric Genetics Consortium (PGC-OCD) was significantly associated with OCS (Pfixed = 3.06 × 10-5). Also, one curated gene set (Mootha Gluconeogenesis) reached Bonferroni-corrected significance (Ngenes = 28, Beta = 0.79, SE = 0.16, Pbon = 0.008). Expression of genes in this set is high at sites of insulin mediated glucose disposal. Dysregulated insulin signaling in the etiology of OCS has been suggested by a previous study describing a genetic overlap of OCS with insulin signaling-related traits in children and adolescents. We report a SNP heritability of 4.1% (P = 0.0044) in the meta-analyzed GWAS, and heritability estimates based on the twin cohorts of 33-43%. Genetic correlation analysis showed that OCS were most strongly associated with OCD (rG = 0.72, p = 0.0007) among all tested psychiatric disorders (N = 11). Of all 97 tested phenotypes, 24 showed a significant genetic correlation with OCS, and 66 traits showed concordant directions of effect with OCS and OCD. OCS have a significant polygenic contribution and share genetic risk with diagnosed OCD, supporting the hypothesis that OCD represents the extreme end of widely distributed OCS in the population.

Genome-wide association study identifies new loci associated with OCD.

To date, four genome-wide association studies (GWAS) of obsessive-compulsive disorder (OCD) have been published, reporting a high single-nucleotide polymorphism (SNP)-heritability of 28% but finding only one significant SNP. A substantial increase in sample size will likely lead to further identification of SNPs, genes, and biological pathways mediating the susceptibility to OCD. We conducted a GWAS meta-analysis with a 2-3-fold increase in case sample size (OCD cases: N = 37,015, controls: N = 948,616) compared to the last OCD GWAS, including six previously published cohorts (OCGAS, IOCDF-GC, IOCDF-GC-trio, NORDiC-nor, NORDiC-swe, and iPSYCH) and unpublished self-report data from 23andMe Inc. We explored the genetic architecture of OCD by conducting gene-based tests, tissue and celltype enrichment analyses, and estimating heritability and genetic correlations with 74 phenotypes. To examine a potential heterogeneity in our data, we conducted multivariable GWASs with MTAG. We found support for 15 independent genome-wide significant loci (14 new) and 79 protein-coding genes. Tissue enrichment analyses implicate multiple cortical regions, the amygdala, and hypothalamus, while cell type analyses yielded 12 cell types linked to OCD (all neurons). The SNP-based heritability of OCD was estimated to be 0.08. Using MTAG we found evidence for specific genetic underpinnings characteristic of different cohort-ascertainment and identified additional significant SNPs. OCD was genetically correlated with 40 disorders or traits-positively with all psychiatric disorders and negatively with BMI, age at first birth and multiple autoimmune diseases. The GWAS meta-analysis identified several biologically informative genes as important contributors to the aetiology of OCD. Overall, we have begun laying the groundwork through which the biology of OCD will be understood and described.

The genetic architecture of youth anxiety: a study protocol.

BACKGROUND: Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. METHODS: The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10-19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. DISCUSSION: Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world.

The Impact of Parental Mental Health Diagnoses, Trauma, and Coping Mechanisms on Their Children's Well-Being.

The transgenerational effects of parental diagnoses, trauma and coping mechanisms on children's internalizing symptoms are not well understood. In a population-based study of 933 families combining data from a web-based survey and the Danish registers, we used an online survey of parents to examine how parental diagnoses, trauma and coping mechanisms affect the development of internalizing symptoms in children aged 6 to 18 years. To account for attrition, we used inverse probability weights in our regression models. Children of parents diagnosed with depression or anxiety displayed more internalizing symptoms than children of controls. Similarly, children of parents who experienced multiple trauma had significantly more internalizing symptoms. In contrast, we observed significantly fewer internalizing symptoms among children of parents who felt they could cope well. The protective effect of parental coping persisted even after adjusting for parental diagnoses or trauma. Interventions boosting parental coping mechanisms might help to prevent the development of internalizing symptoms in children even among patients who have been diagnosed with depression or anxiety or experienced a high trauma load.

Depression pathophysiology, risk prediction of recurrence and comorbid psychiatric disorders using genome-wide analyses.

Depression is a common psychiatric disorder and a leading cause of disability worldwide. Here we conducted a genome-wide association study meta-analysis of six datasets, including >1.3 million individuals (371,184 with depression) and identified 243 risk loci. Overall, 64 loci were new, including genes encoding glutamate and GABA receptors, which are targets for antidepressant drugs. Intersection with functional genomics data prioritized likely causal genes and revealed new enrichment of prenatal GABAergic neurons, astrocytes and oligodendrocyte lineages. We found depression to be highly polygenic, with ~11,700 variants explaining 90% of the single-nucleotide polymorphism heritability, estimating that >95% of risk variants for other psychiatric disorders (anxiety, schizophrenia, bipolar disorder and attention deficit hyperactivity disorder) were influencing depression risk when both concordant and discordant variants were considered, and nearly all depression risk variants influenced educational attainment. Additionally, depression genetic risk was associated with impaired complex cognition domains. We dissected the genetic and clinical heterogeneity, revealing distinct polygenic architectures across subgroups of depression and demonstrating significantly increased absolute risks for recurrence and psychiatric comorbidity among cases of depression with the highest polygenic burden, with considerable sex differences. The risks were up to 5- and 32-fold higher than cases with the lowest polygenic burden and the background population, respectively. These results deepen the understanding of the biology underlying depression, its disease progression and inform precision medicine approaches to treatment.

Drinking to Cope Mediates the Association between Dyadic Conflict and Drinking Behavior: A Study of Romantic Couples during the COVID-19 Pandemic.

The COVID-19 pandemic spurred public health measures to reduce viral spread. Concurrently, increases in alcohol consumption and conflict in romantic partnerships were observed. Pre-pandemic research demonstrated a bidirectional association between couples' conflict and drinking. Recent research shows one's drinking motives (proximal predictors of drinking behavior) can influence another person's drinking in close relationships. It is possible that individuals are drinking to cope with distress following romantic conflict. The current study examined 348 cohabitating couples during the first lockdown in the spring of 2020. Our analyses examined coping motives as a mediator between dyadic conflict and drinking behavior using actor-partner interdependence models. Results showed that conflict was associated with greater reports of own drinking in gendered (distinguishable) and nongendered (indistinguishable) analyses through coping motives. Further, in mixed-gender couples, men partners' coping motives predicted less drinking in women, while women partners' coping motives predicted marginally more drinking in men. Partner effects may have been observed due to the increased romantic partner influence during the COVID-19 lockdown. While these results suggest that men's coping motives may be protective against women's drinking, more concerning possibilities are discussed. The importance of considering dyadic influences on drinking is highlighted; clinical and policy implications are identified.

Associations of active and passive smartphone use with measures of youth mental health during the COVID-19 pandemic.

Smartphone use provides a significant amount of screen-time for youth, and there have been growing concerns regarding its impact on their mental health. While time spent in a passive manner on the device is frequently considered deleterious, more active engagement with the phone might be protective for mental health. Recent developments in mobile sensing technology provide a unique opportunity to examine behaviour in a naturalistic manner. The present study sought to investigate, in a sample of 451 individuals (mean age 20.97 years old, 83% female), whether the amount of time spent on the device, an indicator of passive smartphone use, would be associated with worse mental health in youth and whether an active form of smartphone use, namely frequent checking of the device, would be associated with better outcomes. The findings highlight that overall time spent on the smartphone was associated with more pronounced internalizing and externalizing symptoms in youth, while the number of unlocks was associated with fewer internalizing symptoms. For externalizing symptoms, there was also a significant interaction between the two types of smartphone use observed. Using objective measures, our results suggest interventions targeting passive smartphone use may contribute to improving the mental health of youth.

Familial traits of bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD could reduce variability and benefit research. Since BD has a robust genetic component, studies can investigate clinical traits that cluster in families to identify phenotypes with a probable genetic basis. METHODS: We conducted a systematic review of the current literature on familial clinical traits of BD. Text screening and data extraction were performed independently by two reviewers, and random effects meta-analysis was used. RESULTS: Of 1117 unique records, 16 studies met inclusion criteria. These studies indicated 14 potentially familial traits of BD: age of onset (OR: 4.50; 95% CI: [3.25, 6.22]), bipolar type (OR: 2.05 [1.50, 2.79]), lithium response (OR: 3.71 [1.28, 10.82]), polarity at onset (OR: 1.17 [1.03, 1.34]), psychotic features (OR: 2.20 [1.51, 3.20]), mood-incongruent psychosis (OR: 2.52 [1.66, 3.83]), puerperal psychosis (OR: 6.54 [2.55, 16.77]), rapid cycling (OR: 4.95 [0.96, 25.40]), suicide attempt (OR: 1.04 [0.65, 1.67]), alcoholism (OR: 1.53 [1.09, 2.16]), obsessive-compulsive disorder (OR: 3.10 [1.31; 7.09]), panic disorder (OR: 2.69 [1.12; 6.48]), social anxiety disorder (OR: 1.00 [0.39, 2.55]), and specific phobia (OR: 1.94 [0.95; 3.96]). For most traits, tests of heterogeneity were significant and publication bias was likely. CONCLUSION: The results of our review and meta-analysis highlight the lack of studies investigating familial clinical traits of BD, despite the need to address heterogeneity. The large degree of variability between studies must be reduced for future research.

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder: A Two-Sample Mendelian Randomization and Population-Based Sibling Comparison Study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. METHODS: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). RESULTS: ADHD and PTSD had consistent rg (rg range, 0.43-0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (ß = 0.367; 95% CI, 0.186-0.552; p = 7.68 × 10-5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10-4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98-3.53). CONCLUSIONS: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.