Heritability of cognitive and emotion processing during functional MRI in a twin sample.

Despite compelling evidence that brain structure is heritable, the evidence for the heritability of task-evoked brain function is less robust. Findings from previous studies are inconsistent possibly reflecting small samples and methodological variations. In a large national twin sample, we systematically evaluated heritability of task-evoked brain activity derived from functional magnetic resonance imaging. We used established standardised tasks to engage brain regions involved in cognitive and emotional functions. Heritability was evaluated across a conscious and nonconscious Facial Expressions of Emotion Task (FEET), selective attention Oddball Task, N-back task of working memory maintenance, and a Go-NoGo cognitive control task in a sample of Australian adult twins (N ranged from 136 to 226 participants depending on the task and pairs). Two methods for quantifying associations of heritability and brain activity were utilised; a multivariate independent component analysis (ICA) approach and a univariate brain region-of-interest (ROI) approach. Using ICA, we observed that a significant proportion of task-evoked brain activity was heritable, with estimates ranging from 23% to 26% for activity elicited by nonconscious facial emotion stimuli, 27% to 34% for N-back working memory maintenance and sustained attention, and 32% to 33% for selective attention in the Oddball task. Using the ROI approach, we found that activity of regions specifically implicated in emotion processing and selective attention showed significant heritability for three ROIs, including estimates of 33%-34% for the left and right amygdala in the nonconscious processing of sad faces and 29% in the medial superior prefrontal cortex for the Oddball task. Although both approaches show similar levels of heritability for the Nonconscious Faces and Oddball tasks, ICA results displayed a more extensive network of heritable brain function, including additional regions beyond the ROI analysis. Furthermore, multivariate twin modelling of both ICA networks and ROI activation suggested a mix of common genetic and unique environmental factors that contribute to the associations between networks/regions. Together, the results indicate a complex relationship between genetic factors and environmental interactions that ultimately give rise to neural activation underlying cognition and emotion.

Negative association between anterior insula activation and resilience during sustained attention: an fMRI twin study.

BACKGROUND: While previous studies have suggested that higher levels of cognitive performance may be related to greater wellbeing and resilience, little is known about the associations between neural circuits engaged by cognitive tasks and wellbeing and resilience, and whether genetics or environment contribute to these associations. METHODS: The current study consisted of 253 monozygotic and dizygotic adult twins, including a subsample of 187 early-life trauma-exposed twins, with functional Magnetic Resonance Imaging data from the TWIN-E study. Wellbeing was measured using the COMPAS-W Wellbeing Scale while resilience was defined as a higher level of positive adaptation (higher levels of wellbeing) in the presence of trauma exposure. We probed both sustained attention and working memory processes using a Continuous Performance Task in the scanner. RESULTS: We found significant negative associations between resilience and activation in the bilateral anterior insula engaged during sustained attention. Multivariate twin modelling showed that the association between resilience and the left and right insula activation was mostly driven by common genetic factors, accounting for 71% and 87% of the total phenotypic correlation between these variables, respectively. There were no significant associations between wellbeing/resilience and neural activity engaged during working memory updating. CONCLUSIONS: The findings suggest that greater resilience to trauma is associated with less activation of the anterior insula during a condition requiring sustained attention but not working memory updating. This possibly suggests a pattern of 'neural efficiency' (i.e. more efficient and/or attenuated activity) in people who may be more resilient to trauma.

Longitudinal associations between resting-state, interregional theta-beta phase-amplitude coupling, psychological distress, and wellbeing in 12-15-year-old adolescents.

Cross-frequency coupling between the phase of slower oscillatory activity and the amplitude of faster oscillatory activity in the brain (phase-amplitude coupling; PAC), is a promising new biological marker for mental health. Prior research has demonstrated that PAC is associated with mental health. However, most research has focused on within-region theta-gamma PAC in adults. Our recent preliminary study found increased theta-beta PAC was associated with increased psychological distress in 12 year olds. It is important to investigate how PAC biomarkers relate to mental health and wellbeing in youth. Thus, in this study, we investigated longitudinal associations between interregional (posterior-anterior cortex) resting-state theta-beta PAC (Modulation Index [MI]), psychological distress and wellbeing in N = 99 adolescents (aged 12-15 years). In the right hemisphere, there was a significant relationship, whereby increased psychological distress was associated with decreased theta-beta PAC and psychological distress increased with increased age. In the left hemisphere, there was a significant relationship, whereby decreased wellbeing was associated with decreased theta-beta PAC and wellbeing scores decreased with increased age. This study presents novel findings demonstrating longitudinal relationships between interregional, resting-state theta-beta PAC and mental health and wellbeing in early adolescents. This EEG marker may facilitate improved early identification of emerging psychopathology.

Associations between mental wellbeing and fMRI neural bases underlying responses to positive emotion in a twin sample.

BACKGROUND: Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment. METHODS: We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task. We used linear mixed models to analyse the association between COMPAS-W scores and emotion-elicited neural activation. Univariate twin modelling was used to evaluate heritability of each brain region. Multivariate twin modelling was used to compare twin pairs to assess the contributions of genetic and environmental factors to this association. RESULTS: Higher levels of wellbeing were associated with greater neural activity in the dorsolateral prefrontal cortex, localised in the right inferior frontal gyrus (IFG), in response to positive emotional expressions of happiness. Univariate twin modelling showed activity in the IFG to have 20% heritability. Multivariate twin modelling suggested that the association between wellbeing and positive emotion-elicited neural activity was driven by common variance from unique environment (r = 0.208) rather than shared genetics. CONCLUSIONS: Higher mental wellbeing may have a basis in greater engagement of prefrontal neural regions in response to positive emotion, and this association may be modifiable by unique life experiences.

Predicting wellbeing over one year using sociodemographic factors, personality, health behaviours, cognition, and life events.

Various sociodemographic, psychosocial, cognitive, and life event factors are associated with mental wellbeing; however, it remains unclear which measures best explain variance in wellbeing in the context of related variables. This study uses data from 1017 healthy adults from the TWIN-E study of wellbeing to evaluate the sociodemographic, psychosocial, cognitive, and life event predictors of wellbeing using cross-sectional and repeated measures multiple regression models over one year. Sociodemographic (age, sex, education), psychosocial (personality, health behaviours, and lifestyle), emotion and cognitive processing, and life event (recent positive and negative life events) variables were considered. The results showed that while neuroticism, extraversion, conscientiousness, and cognitive reappraisal were the strongest predictors of wellbeing in the cross-sectional model, while extraversion, conscientiousness, exercise, and specific life events (work related and traumatic life events) were the strongest predictors of wellbeing in the repeated measures model. These results were confirmed using tenfold cross-validation procedures. Together, the results indicate that the variables that best explain differences in wellbeing between individuals at baseline can vary from the variables that predict change in wellbeing over time. This suggests that different variables may need to be targeted to improve population-level compared to individual-level wellbeing.

TWIN-10: protocol for a 10-year longitudinal twin study of the neuroscience of mental well-being and resilience.

INTRODUCTION: Mental well-being is a core component of mental health, and resilience is a key process of positive adaptive recovery following adversity. However, we lack an understanding of the neural mechanisms that contribute to individual variation in the trajectories of well-being and resilience relative to risk. Genetic and/or environmental factors may also modulate these mechanisms. The aim of the TWIN-10 Study is to characterise the trajectories of well-being and resilience over 12 years across four timepoints (baseline, 1 year, 10 years, 12 years) in 1669 Australian adult twins of European ancestry (to account for genetic stratification effects). To this end, we integrate data across genetics, environment, psychological self-report, neurocognitive performance and brain function measures of well-being and resilience. METHODS AND ANALYSIS: Twins who took part in the baseline TWIN-E Study will be invited back to participate in the TWIN-10 Study, at 10-year and 12-year follow-up timepoints. Participants will complete an online battery of psychological self-reports, computerised behavioural assessments of neurocognitive functions and MRI testing of the brain structure and function during resting and task-evoked scans. These measures will be used as predictors of the risk versus resilience trajectory groups defined by their changing levels of well-being and illness symptoms over time as a function of trauma exposure. Structural equation models will be used to examine the association between the predictors and trajectory groups of resilience and risk over time. Univariate and multivariate twin modelling will be used to determine heritability of the measures, as well as the shared versus unique genetic and environmental contributions. ETHICS AND DISSEMINATION: This study involves human participants. This study was approved by the University of New South Wales Human Research Ethics Committee (HC180403) and the Scientific Management Panel of Neuroscience Research Australia Imaging (CX2019-05). Results will be disseminated through publications and presentations to the public and the academic community. Participants gave informed consent to participate in the study before taking part.

Wellbeing and brain structure: A comprehensive phenotypic and genetic study of image-derived phenotypes in the UK Biobank.

Wellbeing, an important component of mental health, is influenced by genetic and environmental factors. Previous association studies between brain structure and wellbeing have typically focused on volumetric measures and employed small cohorts. Using the UK Biobank Resource, we explored the relationships between wellbeing and brain morphometrics (volume, thickness and surface area) at both phenotypic and genetic levels. The sample comprised 38,982 participants with neuroimaging and wellbeing phenotype data, of which 19,234 had genotypes from which wellbeing polygenic scores (PGS) were calculated. We examined the association of wellbeing phenotype and PGS with all brain regions (including cortical, subcortical, brainstem and cerebellar regions) using multiple linear models, including (1) basic neuroimaging covariates and (2) additional demographic factors that may synergistically impact wellbeing and its neural correlates. Genetic correlations between genomic variants influencing wellbeing and brain structure were also investigated. Small but significant associations between wellbeing and volumes of several cerebellar structures (ß = 0.015-0.029, PFDR  = 0.007-3.8 × 10-9 ), brainstem, nucleus accumbens and caudate were found. Cortical associations with wellbeing included volume of right lateral occipital, thickness of bilateral lateral occipital and cuneus, and surface area of left superior parietal, supramarginal and pre-/post-central regions. Wellbeing-PGS was associated with cerebellar volumes and supramarginal surface area. Small mediation effects of wellbeing phenotype and PGS on right VIIIb cerebellum were evident. No genetic correlation was found between wellbeing and brain morphometric measures. We provide a comprehensive overview of wellbeing-related brain morphometric variation. Notably, small effect sizes reflect the multifaceted nature of this concept.

A Web-Based Well-being Program for Health Care Workers (Thrive): Protocol for a Randomized Controlled Trial.

BACKGROUND: Mental health has come to be understood as not merely the absence of mental illness but also the presence of mental well-being, and recent interventions have sought to increase well-being in various populations. A population that deserves particular attention is that of health care workers, whose occupations entail high levels of stress, especially given the ongoing COVID-19 pandemic. A neuroscience-based web-based well-being program for health care workers-the Thrive program-has been newly developed to promote habits and activities that contribute to brain health and overall mental well-being. OBJECTIVE: This paper describes the protocol for a randomized controlled trial whose objective is to evaluate the Thrive program in comparison with an active control condition to measure whether the program is effective at increasing well-being and decreasing symptoms of psychological distress in health care workers at a designated Australian hospital. METHODS: The trial will comprise two groups (intervention vs active control) and 4 measurement occasions over a 12-week period. A survey will be administered in each of weeks 0, 4, 8, and 12, and the well-being program will be delivered in weeks 1-7 (via web-based video presentations or digital pamphlets). Each of the 4 surveys will comprise a range of questionnaires to measure well-being, psychological distress, and other key variables. The planned analyses will estimate group-by-time interaction effects to test the hypothesis that mental health will increase over time in the intervention condition relative to the active control condition. RESULTS: The Thrive program was delivered to a small number of wards at the hospital between February 2021 and July 2021, and it will be delivered to the remaining wards from October 2021 to December 2021. A power calculation has recommended a sample size of at least 200 participants in total. A linear mixed model will be used to estimate the interaction effects. CONCLUSIONS: This trial seeks to evaluate a new web-based well-being program for health care workers at a major public hospital. It will contribute to the growing body of research on mental well-being and ways to promote it. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621000027819; https://tinyurl.com/58wwjut9. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34005.

Phenotypic and genetic analysis of a wellbeing factor score in the UK Biobank and the impact of childhood maltreatment and psychiatric illness.

Wellbeing is an important aspect of mental health that is moderately heritable. Specific wellbeing-related variants have been identified via GWAS meta-analysis of individual questionnaire items. However, a multi-item within-subject index score has potential to capture greater heritability, enabling improved delineation of genetic and phenotypic relationships across traits and exposures that are not possible on aggregate-data. This research employed data from the UK Biobank resource, and a wellbeing index score was derived from indices of happiness and satisfaction with family/friendship/finances/health, using principal component analysis. GWAS was performed in Caucasian participants (N = 129,237) using the derived wellbeing index, followed by polygenic profiling (independent sample; N = 23,703). The wellbeing index, its subcomponents, and negative indicators of mental health were compared via phenotypic and genetic correlations, and relationships with psychiatric disorders examined. Lastly, the impact of childhood maltreatment on wellbeing was investigated. Five independent genome-wide significant loci for wellbeing were identified. The wellbeing index had SNP-heritability of ~8.6%, and stronger phenotypic and genetic correlations with its subcomponents (0.55-0.77) than mental health phenotypes (-0.21 to -0.39). The wellbeing score was lower in participants reporting various psychiatric disorders compared to the total sample. Childhood maltreatment exposure was also associated with reduced wellbeing, and a moderate genetic correlation (rg = ~-0.56) suggests an overlap in heritability of maltreatment with wellbeing. Thus, wellbeing is negatively associated with both psychiatric disorders and childhood maltreatment. Although notable limitations, biases and assumptions are discussed, this within-cohort study aids the delineation of relationships between a quantitative wellbeing index and indices of mental health and early maltreatment.

Grey matter covariation and the role of emotion reappraisal in mental wellbeing and resilience after early life stress exposure.

Resilience is a process of adaptive recovery crucial in maintaining mental wellbeing after stress exposure. A psychological factor known to buffer stress and promote positive wellbeing outcomes is the ability to regulate emotions. However, the neural networks underlying resilience, and the possible mediating role of emotion regulation, remain largely unknown. Here, we examined the association between resilience and grey matter covariation (GMC) in healthy adults with and without early life stress (ELS) exposure, and whether emotion regulation mediated this brain-resilience association. Source-based morphometry was used to identify spatial patterns of common GMC in 242 healthy participants. Wellbeing was measured using the COMPAS-W Wellbeing Scale. Linear mixed models were run to establish associations between GMC and wellbeing scores. Moderated mediation models were used to examine a conditional mediating effect of emotion regulation on the brain-wellbeing relationship, moderated by ELS exposure. Distinct ELS-related morphometric patterns were found in association with resilience. In participants without ELS exposure, decreased GMC in the temporo-parietal regions was associated with wellbeing. In participants with ELS exposure, we observed increased patterns of covariation in regions related to the salience and executive control networks, and decreased GMC in temporo-parietal areas, which were associated with resilience. Cognitive reappraisal mediated the brain-wellbeing relationship in ELS-exposed participants only. Patterns of stronger GMC in regions associated with emotional and cognitive functioning in ELS-exposed participants with high levels of wellbeing may indicate possible neural signatures of resilience. This may be further heightened by utilising an adaptive form of emotion regulation.

Six-Week Online Multi-component Positive Psychology Intervention Improves Subjective Wellbeing in Young Adults.

Improving mental wellbeing has a range of benefits for society, including increased productivity, longevity, and resiliency. However, interventions designed to improve mental wellbeing are often only compared to waitlist controls, leaving uncertainty regarding the mechanisms of their effectiveness. The current study in 326 participants assessed a six-week positive psychology intervention against an active control (n = 163) in an online randomized control trial. Outcome measures included life satisfaction, wellbeing (subjective and psychological wellbeing), stress, depression and anxiety symptoms, and self-compassion. The potential moderating effect of participating during the ongoing COVID-19 pandemic was also explored. The intervention group showed greater improvements in life satisfaction by week six (ß = 0.18, p = .014) and were maintained through to 7 weeks post-baseline (ß = 0.23, t = 3.07, p = .002) and remained significant when accounting for COVID-19 restrictions. An improvement in composite wellbeing from baseline to 7 weeks post-baseline was detected when accounting for COVID-19 restrictions. Composite wellbeing and total depression and anxiety symptoms improved significantly more in the intervention group for participants with low baseline resiliency resources. These findings support the efficacy of using online multi-component positive psychology interventions in boosting wellbeing and reducing distress symptoms particularly in individuals with fewer resiliency resources who may need added support. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10902-021-00449-3.

Basal ganglia correlates of wellbeing in early adolescence.

It has been suggested that biological markers that define mental health are different to those that define mental illness. The basal ganglia changes dramatically over adolescence and has been linked to wellbeing and mental health disorders in young people. However, there remains a paucity of research on wellbeing and brain structure in early adolescence. This cross-sectional study examined relationships between grey matter volume (GMV) of basal ganglia regions (caudate, putamen, pallidum and nucleus accumbens) and self-reported wellbeing (COMPAS-W), in a sample of Australian adolescents aged 12 years (N = 49, M = 12.6, 46.9% female). Significant negative associations were found between left hemisphere caudate GMV and scores on 'total wellbeing', 'composure' and 'positivity'. The results of this study indicate that smaller caudate GMV at age 12 is linked to increased subjective wellbeing. While seemingly counter-intuitive, our finding is consistent with previous research of decreased GMV in the pons and increased COMPAS-W scores in adults. Our results suggest that protective neurobiological factors may be identifiable early in adolescence and be linked to specific types of wellbeing (such as positive affect and optimism). This has implications for interventions targeted at building resilience against mental health disorders in young people.

Building a transdisciplinary expert consensus on the cognitive drivers of performance under pressure: An international multi-panel Delphi study.

Introduction: The ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure. Methods: International experts were recruited from four performance domains [(i) Defense; (ii) Competitive Sport; (iii) Civilian High-stakes; and (iv) Performance Neuroscience]. Experts rated constructs from the Research Domain Criteria (RDoC) framework (and several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance. Results: Sixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. The following 10 constructs reached consensus across all four panels (in order of overall ranking): (1) Attention; (2) Cognitive Control-Performance Monitoring; (3) Arousal and Regulatory Systems-Arousal; (4) Cognitive Control-Goal Selection, Updating, Representation, and Maintenance; (5) Cognitive Control-Response Selection and Inhibition/Suppression; (6) Working memory-Flexible Updating; (7) Working memory-Active Maintenance; (8) Perception and Understanding of Self-Self-knowledge; (9) Working memory-Interference Control, and (10) Expert-suggested-Shifting. Discussion: Our results identify a set of transdisciplinary neuroscience-informed constructs, validated through expert consensus. This expert consensus is critical to standardizing cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimization.

Emotional face processing correlates with depression/anxiety symptoms but not wellbeing in non-clinical adults: An event-related potential study.

Whilst alterations in emotional face processing, as indicated by event-related potentials (ERPs), are associated with depression and anxiety symptoms in clinical and non-clinical samples, it has remained unclear whether they are related to mental wellbeing. The current study aimed to address this question in a non-clinical sample. The analysis included 402 adult twins from the TWIN-E study. The COMPAS-W and the Depression Anxiety Stress Scale (DASS-42) were used to measure mental wellbeing and depression/anxiety symptoms, respectively. Participants viewed facial expressions under Unmasked (conscious) and Masked (subliminal) conditions while ERPs were recorded. The associations of emotion processing with mental wellbeing and depression/anxiety symptoms were assessed using multivariate linear mixed models. There was a strong association between depression/anxiety symptoms and the N170 amplitude difference for the Fear - Happy contrast in the Masked condition after controlling for wellbeing scores (B = 0.34, p < .001). Specifically, higher depression/anxiety symptoms were associated with a lack of differentiation between fearful and happy faces. No associations were found between emotional face processing and mental wellbeing scores. These results indicate that even within a non-clinical sample, alterations in emotional ERPs, namely the N170, reflect differences in depression/anxiety symptoms rather than differences in wellbeing. Furthermore, this effect was limited to automatic processing, rather than conscious processing of emotional stimuli, suggesting the observed differences apply only to the subconscious pathway.

Approach Coping Mitigates Distress of COVID-19 Isolation for Young Men With Low Well-Being in a Sample of 1,749 Youth From Australia and the USA.

The unprecedented COVID-19 pandemic has led to lockdowns across the world with people being separated from their loved ones including partners, family, and friends. Here, using a large sample of 1,749 Australians and Americans, we investigated the impact of COVID-19 isolation on younger populations (13-25 years), and the influence of coping strategies and mental well-being on this impact. Overall, COVID-19 isolation had a more negative impact on adolescence (13-17 years) than young adulthood (18-25 years), but with no difference apparent between men and women, or between Australian and American residents. However, a deeper analysis revealed a gender-specific effect: the type of coping strategies differentially influenced the negative impact of COVID-19 isolation on men with various levels of well-being, an interaction effect not apparent in women. For men with lower levels of mental well-being, COVID-19 isolation appeared to have a less negative impact on them if they used more approach-oriented coping strategies (e.g., actively focusing on the problem). Our results provide cross-sectional evidence for a differential impact on young men at low levels of wellbeing by pandemic isolation. In sum, young men and adolescent boys with lower well-being coped better with COVID-19 isolation when they used more approach coping strategies.

The impact of online brain training exercises on experiences of depression, anxiety and emotional wellbeing in a twin sample.

This study assessed the effectiveness of cognitive and emotional brain training and transfer effects to wellbeing and depression and anxiety symptoms. 352 healthy adult twins were randomised to a training group where they were asked to play brain training games over a 30-day period, or a waitlist control group. This study focused on the impact of the brain training on explicit and implicit emotional cognition, and analysed effects using both Intention-To-Treat (ITT) and Per-Protocol (PP) approaches. Both analyses revealed significant training effects for improvement in the explicit identification of fear expressions (ITT: p < 0.001, d = 0.33; PP training 3 h+: p < 0.001, d = 0.55), and a reduction in implicit bias for anger expressions amongst males (ITT: p < 0.001, d = 0.94; PP training 3 h+: p = 0.04, d = 0.90). Female participants also showed improvements in implicit bias for happy expressions (ITT: p = 0.003, d = 0.34; PP training 3 h+: p = 0.03, d = 0.47). Improvements resulting from training in emotional cognition did not directly improve wellbeing, depression or anxiety symptoms. Regression modelling also suggested training improvements in emotional cognition yielded no indirect transfer effects for the mental health and wellbeing measures. The results suggest brain training in healthy populations has potential for improving emotional cognition, but the subsequent impact on improving wellbeing and mental health symptoms is still equivocal.

The neuroscience of positive emotions and affect: Implications for cultivating happiness and wellbeing.

This review paper provides an integrative account regarding neurophysiological correlates of positive emotions and affect that cumulatively contribute to the scaffolding for happiness and wellbeing in humans and other animals. This paper reviews the associations among neurotransmitters, hormones, brain networks, and cognitive functions in the context of positive emotions and affect. Consideration of lifespan developmental perspectives are incorporated, and we also examine the impact of healthy social relationships and environmental contexts on the modulation of positive emotions and affect. The neurophysiological processes that implement positive emotions are dynamic and modifiable, and meditative practices as well as flow states that change patterns of brain function and ultimately support wellbeing are also discussed. This review is part of "The Human Affectome Project" (http://neuroqualia.org/background.php), and in order to advance a primary aim of the Human Affectome Project, we also reviewed relevant linguistic dimensions and terminology that characterizes positive emotions and wellbeing. These linguistic dimensions are discussed within the context of the neuroscience literature with the overarching goal of generating novel recommendations for advancing neuroscience research on positive emotions and wellbeing.

Diverse phenotypic measurements of wellbeing: Heritability, temporal stability and the variance explained by polygenic scores.

Wellbeing, a key aspect of mental health, is moderately heritable with varying estimates reported from independent studies employing a variety of instruments. Recent genome-wide association studies (GWAS) have enabled the construction of polygenic scores (PGS) for wellbeing, providing the opportunity for direct comparisons of the variance explained by PGS for different instruments commonly employed in the field. Nine wellbeing measurements (multi-item and single-item), two personality domains (NEO-FFI neuroticism and extraversion), plus the depression domain of the DASS-42 were drawn from a larger self-report battery applied to the TWIN-E study-an Australian longitudinal twin cohort (N = 1660). Heritability was estimated using univariate twin modeling and 12-month test-retest reliability was estimated using intra-class correlation. PGS were constructed using wellbeing GWAS summary-statistics from Baselmans et al. (Nat Genet. 2019), and the variance explained estimated using linear models. Last, a GWAS was performed using COMPAS-W, a quantitative composite wellbeing measure, to explore its utility in genomic studies. Heritability estimates ranged from 23% to 47% across instruments, and multi-item measures showed higher heritability and test-retest reliability than single-item measures. The variance explained by PGS was ~0.5% to 1.5%, with considerable variation between measures, and within each measure over 12 months. Five loci with suggestive association (p < 1 × 10-5 ) were identified from this initial COMPAS-W wellbeing GWAS. This work highlights the variability across measures currently employed in wellbeing research, with multi-item and composite measures favored over single-item measures. While wellbeing PGS are useful in a research setting, they explain little of the phenotypic variance, highlighting gaps for improved gene discovery.

Electroencephalography profiles as a biomarker of wellbeing: A twin study.

Alterations to electroencephalography (EEG) power have been reported for psychiatric conditions such as depression and anxiety, but not for mental wellbeing in a healthy population. This study examined the resting EEG profiles associated with mental wellbeing, and how genetics and environment contribute to these associations using twin modelling. Mental wellbeing was assessed using the COMPAS-W Wellbeing Scale which measures both subjective and psychological wellbeing. In 422 healthy adult monozygotic and dizygotic twins aged 18-61 years, we examined the association between mental wellbeing and EEG power (alpha, beta, theta, delta) using linear mixed models. This was followed by univariate and multivariate twin modelling to assess the heritability of wellbeing and EEG power, and whether the association was driven by shared genetics or environment. A significant association between wellbeing and an interaction of alpha, beta, and delta (ABD) power was found (ß = -0.33, p < 0.001) whereby a profile of high alpha and delta and low beta was associated with higher wellbeing, independent of depression and anxiety symptoms. This finding was supported by a five-fold cross-validation analysis. A significant genetic correlation (rG = -0.43) was found to account for 94% of the association between wellbeing and the EEG power interaction. Together, this study has identified a novel EEG profile with a common genetic component that may be a potential biomarker of mental wellbeing. Future studies need to clarify the causal direction of this association.