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.

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.

Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

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.

Are all behavioral reward benefits created equally? An EEG-fMRI study.

Reward consistently boosts performance in cognitive tasks. Although many different reward manipulations exist, systematic comparisons are lacking. Reward effects on cognitive control are usually studied using monetary incentive delay (MID; cue-related reward information) or stimulus-reward association (SRA; target-related reward information) tasks. While for MID tasks, evidence clearly implicates reward-triggered global increases in proactive control, it is unclear how reward effects arise in SRA tasks, and in how far such mechanisms overlap during task preparation and target processing. Here, we address these questions with simultaneous EEG-fMRI using a Stroop task with four different block types. In addition to MID and SRA blocks, we used an SRA-task modification with reward-irrelevant cues (C-SRA) and regular reward-neutral Stroop-task blocks. Behaviorally, we observed superior performance for all reward conditions compared to Neutral, and more pronounced reward effects in the SRA and C-SRA blocks, compared to MID blocks. The fMRI data showed similar reward effects in value-related areas for events that signaled reward availability (MID cues and (C-)SRA targets), and comparable reward modulations in cognitive-control regions for all targets regardless of block type. This result pattern was echoed by the EEG data, showing clear markers of valuation and cognitive control, which only differed during task preparation, whereas reward-related modulations during target processing were again comparable across block types. Yet, considering only cue-related fMRI data, C-SRA cues triggered preparatory control processes beyond reward-unrelated MID cues, without simultaneous modulations in typical reward areas, implicating enhanced task preparation that is not directly driven by a concurrent neural reward-anticipation response.

Neural correlates of reward-related response tendencies in an equiprobable Go/NoGo task.

Previous research has shown that motivational signals bias action over inaction, which may be due to putative inherent valence-action mappings, similar to those observed in the emotional domain. In the present functional magnetic resonance imaging (fMRI) study we sought to investigate the neural underpinnings of such reward-related response tendencies, and in particular, how valence-action compatibility effects arising from predominant response tendencies are reflected at the neural level, and whether overlapping emotional valence amplifies these effects. To this end, we employed an equiprobable (50:50) Go/NoGo task in which reward (reward/no-reward) and response mode (Go/NoGo) were signaled by orthogonal features of number targets that were overlaid on emotional images (positive, neutral, negative). Reward-related targets led to response facilitation (faster Go responses) and impairment in withholding responses (more NoGo commission errors), consistent with a reward-induced action bias. This pattern was paralleled by modulations in the left dorsolateral prefrontal cortex (dlPFC), with increased activity in no-reward as compared to reward-related Go trials, and the reversed pattern in NoGo trials. Albeit being processed in ventral visual areas, emotional background did not modulate performance in the present task, suggesting that irrelevant emotional information is globally outweighed by reward. In the current paradigm, which neither favors Go responses generally nor allows for differential preparation in Go versus NoGo trials, reward-related targets promote action over inaction. In turn, additional effort is needed to inhibit responses to these targets as well as to initiate responses to (less salient) no-reward targets, which may be considered as a downside of direct stimulus-reward associations.

Smiling faces and cash bonuses: Exploring common affective coding across positive and negative emotional and motivational stimuli using fMRI.

Although it is clear that emotional and motivational manipulations yield a strong influence on cognition and behaviour, these domains have mostly been investigated in independent research lines. Therefore, it remains poorly understood how far these affective manipulations overlap in terms of their underlying neural activations, especially in light of previous findings that suggest a shared valence mechanism across multiple affective processing domains (e.g., monetary incentives, primary rewards, emotional events). This is particularly interesting considering the commonality between emotional and motivational constructs in terms of their basic affective nature (positive vs. negative), but dissociations in terms of instrumentality, in that only reward-related stimuli are typically associated with performance-contingent outcomes. Here, we aimed to examine potential common neural processes triggered by emotional and motivational stimuli in matched tasks within participants using functional magnetic resonance imaging (fMRI). Across tasks, we found shared valence effects in the ventromedial prefrontal cortex and left inferior frontal gyrus (part of dorsolateral prefrontal cortex), with increased activity for positive and negative stimuli, respectively. Despite this commonality, emotion and reward tasks featured differential behavioural patterns in that negative valence effects (performance costs) were exclusive to emotional stimuli, while positive valence effects (performance benefits) were only observed for reward-related stimuli. Overall, our data suggest a common affective coding mechanism across different task domains and support the idea that monetary incentives entail signed basic valence signals, above and beyond the instruction to perform both gain and loss trials as accurately as possible to maximise the outcome.

Associations between schizotypy and cerebral laterality.

Atypical lateralization for language has been found in schizophrenia, suggesting that language and thought disorders on the schizophrenia spectrum may be due to left hemispheric dysfunction. However, research with those with non-clinical schizotypy has been inconsistent, with some studies finding reduced or reversed language laterality (particularly with positive schizotypal traits), and others finding typical left hemispheric specialization. The aim of the current study was to use both a behavioural (dual reading-finger tapping) task and an functional magnetic resonance imaging lexical decision task to investigate language laterality in a university sample of high- and low-schizotypal adults. Findings revealed no evidence for atypical lateralization in our sample for both overall schizotypy (measured by the Oxford-Liverpool Inventory of Feelings and Experiences) and positive schizotypy (measured by the Unusual Experiences subscale) groups. Our findings provide further evidence that non-clinical schizotypy is not associated with atypical language laterality.

Resilience to Stress and Adversity: A Narrative Review of the Role of Positive Affect.

The modern conception of mental health encompasses not only mental illness but also mental wellbeing, including positive emotional states and other forms of positive experience. Accordingly, research on resilience - that is, recovery or adaptation following adversity - has recently expanded to consider the roles of positive affect in the resilience process. To review this research, we performed a keyword search of all peer-reviewed journals within the American Psychological Association's PsycInfo database, retrieving all studies of positive affect in the context of resilience. These studies measured positive affect either as the outcome of the resilience process or as a resilience resource in its own right. With positive affect as the outcome, the literature suggests that various resilience resources can promote positive affect following a stressor, especially positive personality traits (eg, hope, optimism, self-compassion) and supportive interpersonal connections. With positive affect as a resilience resource, the literature suggests that higher levels of positive affect may protect individuals from the impact of stress on a number of outcomes, such as depression and trauma symptoms. In all, the reviewed research showcases a wide range of stressors, resources, and outcomes, and there are numerous openings for future discoveries in this promising area of inquiry.

The effect of target-related and target-irrelevant novel stimuli on response behaviour.

Novel events catch our attention, which can influence performance of a task. Whether this attentional capture by novelty benefits or impairs performance depends on several factors, such as the relevance of the stimulus, task requirements, and the timing of the event. Additionally, it has been argued that novel stimuli can hold intrinsic reward value, which may directly affect approach motivation, similar to positive valence stimuli. This link between novelty and approach/avoid behaviour has not been investigated directly. Here, we investigated whether stimulus novelty interacts with response behaviour in an approach/avoidance task, and whether these effects depend on the task relevance of novelty and stimulus timing. In experiment 1, participants gave an approach or avoid response dependent on a shape (diamond or square) presented at different stimulus onset asynchronies (SOA) following a novel or familiar scene (target-irrelevant novelty). In experiment 2, participants had to approach or avoid a novel or familiar image depending on the content (indoor/outdoor; target-related novelty). A shape was presented at different SOA. Results of a linear mixed model showed novelty-induced performance costs as demonstrated by longer RT and lower accuracy when novelty was target-relevant, likely due to attentional lingering at novel images. When images were target-irrelevant, approach but not avoid responses were faster for familiar versus novel images at 200 ms SOA only. Thus, novelty had a differentially pronounced detrimental effect on performance. These observations confirm that processing of novel stimuli generally depends on stimulus relevance, and tentatively suggests that differential processing of novel and familiar images is intensified by motivated approach behaviour.

Brain activity in bilingual developmental dyslexia: an fMRI study.

The aim of this study was to identify the neural substrates of an adult English-German bilingual with dyslexia (in both languages) during lexical decision-making using functional magnetic resonance imaging (fMRI). A lexical decision task with five conditions in a block design was employed (nonverbal shape judgment, lettercase judgment, regular word judgment, irregular word judgment, and nonword judgment), and the activation was compared to a non-dyslexic control bilingual and a control monolingual participant. Both of the control participants matched the dyslexic bilingual BK on age, sex, IQ, handedness, and education level. Results indicated that the bilingual adult with dyslexia was strongly right lateralized for stimuli that required phonological processing, a profile that differed particularly from the activation observed from the monolingual participant. These results are consistent with the idea of increased activation (mostly in the right hemisphere) during linguistic tasks in adults with dyslexia and in late proficient bilinguals relative to monolinguals. Findings also suggest that the additional activation observed in both of the bilinguals are similar, suggesting that these effects are not additive in the dyslexic bilingual.

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.

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.

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.

Associations between different white matter properties and reward-based performance modulation.

Humans can be motivated by the prospect of gaining a reward. However, the extent to which we are affected by reward information differs from person to person. A possible mechanism underlying these inter-individual differences may be alterations in white matter (WM) microstructure; however, the relationship between WM properties and reward-based behaviour in healthy participants has not yet been explored. Here, we used a fixel-based approach to investigate potential associations between WM tracts and performance in a reward-cuing task. We found that WM properties in the corpus callosum, right uncinate fasciculus, left ventral cingulum, and accumbofrontal tracts were inversely related to reward-triggered performance benefits (indexed by faster reaction times). Moreover, smaller WM property values in the corpus callosum, uncinate fasciculus, and accumbofrontal tracts were associated with higher scores on the Behavioral Inhibition System scale, reflecting greater sensitivity to potential punishment. Finally, we also observed associations between functional hemodynamic activity in the ventral striatum and WM microstructure. The finding that reward-based behavioural benefits are related to lower measures of WM tracts is in contrast to studies linking higher WM metrics to superior cognitive performance. We interpret the current pattern in terms of higher susceptibility to motivationally relevant stimuli, which is in line with the current and previous studies reporting inverse relationships between WM properties and motivational traits. Taking a broader perspective, such propensities may only be beneficial up to a certain point, at which these may become detrimental to performance and even manifest as impulsive and addictive behaviour.

Neural underpinnings of valence-action interactions triggered by cues and targets in a rewarded approach/avoidance task.

Incentive-valence signals have a large impact on our actions in everyday life. While it is intuitive (and most often beneficial) to approach positive and avoid negative stimuli, these prepotent response tendencies can also be maladaptive, as exemplified by clinical conditions such as overeating or pathological gambling. We have recently shown that targets associated with monetary incentives can trigger such valence-action biases (target condition), and that these are absent when valence and action information are provided by advance cues (cue condition). Here, we explored the neural correlates underlying the absence of the behavioral bias in this condition using fMRI. Specifically, we tested in how far valence and action information are integrated at all in the cue condition (where no behavioral biases are observed), assessing activity at the moment of the cue (mainly preparation) and the target (mainly implementation). The cue-locked data was dominated by main effects of valence with increased activity for incentive versus no-incentive cues in a network including anterior insula, premotor cortex, (mostly ventral) striatum (voxel-wise analysis), and across five predefined regions of interest (ROI analysis). Only one region, the anterior cingulate cortex, featured a valence-action interaction, with increased activity for win-approach compared to no-incentive-approach cues. The target-locked data revealed a different interaction pattern with increased activity in loss-approach as compared to win-approach targets in the cerebellum (voxel-wise) and across all ROIs. For comparison, the uncued target condition (target-locked data only) featured valence and action main effects (incentive > no-incentive targets; approach > avoid targets), but no interactions. The results resonate with the common observations that performance benefits after incentive-valence cues are promoted by increased preparatory control. Moreover, the data provide support for the idea that valence and action information are integrated according to an evolutionary benefit (cue-locked), requiring additional neural resources to implement non-intuitive valence-action mappings (target-locked).

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.

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.