Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study.

BACKGROUND: The timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted. METHODS: In this Registered Report, we triangulated evidence from different causal inference methods using a new wave of data (N = 13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess the causal links between age at menarche and different domains of adolescent mental health. RESULTS: Our results supported the hypothesis that earlier age at menarche is associated with elevated depressive symptoms in early adolescence based on multiple regression (ß = - 0.11, 95% CI [- 0.12, - 0.09], pone-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (ß = - 0.07, 95% CI [- 0.13, 0.00], pone-tailed = 0.03), but the effect was small, corresponding to just a 0.06 standard deviation increase in depressive symptoms with each earlier year of menarche. There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], pone-tailed = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Multivariable MR analyses accounting for the genetic overlap between age at menarche and childhood body size provided some evidence of confounding. Meanwhile, we found little consistent evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding. CONCLUSIONS: We found evidence that age at menarche affected diagnoses of adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.

Correction to: The complex neurobiology of resilient functioning after childhood maltreatment.

An amendment to this paper has been published and can be accessed via the original article.

The complex neurobiology of resilient functioning after childhood maltreatment.

BACKGROUND: Childhood maltreatment has been associated with significant impairment in social, emotional and behavioural functioning later in life. Nevertheless, some individuals who have experienced childhood maltreatment function better than expected given their circumstances. MAIN BODY: Here, we provide an integrated understanding of the complex, interrelated mechanisms that facilitate such individual resilient functioning after childhood maltreatment. We aim to show that resilient functioning is not facilitated by any single 'resilience biomarker'. Rather, resilient functioning after childhood maltreatment is a product of complex processes and influences across multiple levels, ranging from 'bottom-up' polygenetic influences, to 'top-down' supportive social influences. We highlight the complex nature of resilient functioning and suggest how future studies could embrace a complexity theory approach and investigate multiple levels of biological organisation and their temporal dynamics in a longitudinal or prospective manner. This would involve using methods and tools that allow the characterisation of resilient functioning trajectories, attractor states and multidimensional/multilevel assessments of functioning. Such an approach necessitates large, longitudinal studies on the neurobiological mechanisms of resilient functioning after childhood maltreatment that cut across and integrate multiple levels of explanation (i.e. genetics, endocrine and immune systems, brain structure and function, cognition and environmental factors) and their temporal interconnections. CONCLUSION: We conclude that a turn towards complexity is likely to foster collaboration and integration across fields. It is a promising avenue which may guide future studies aimed to promote resilience in those who have experienced childhood maltreatment.

Mood and neural responses to social rejection do not seem to be altered in resilient adolescents with a history of adversity.

Childhood adversity (CA) increases the risk of subsequent mental health problems. Adolescent social support (from family and/or friends) reduces the risk of mental health problems after CA. However, the mechanisms of this effect remain unclear, and we speculate that they are manifested on neurodevelopmental levels. Therefore, we investigated whether family and/or friendship support at ages 14 and 17 function as intermediate variables for the relationship between CA before age 11 and affective or neural responses to social rejection feedback at age 18. We studied 55 adolescents with normative mental health at age 18 (26 with CA and therefore considered "resilient"), from a longitudinal cohort. Participants underwent a Social Feedback Task in the magnetic resonance imaging scanner. Social rejection feedback activated the dorsal anterior cingulate cortex and the left anterior insula. CA did not predict affective or neural responses to social rejection at age 18. Yet, CA predicted better friendships at age 14 and age 18, when adolescents with and without CA had comparable mood levels. Thus, adolescents with CA and normative mood levels have more adolescent friendship support and seem to have normal mood and neural responses to social rejection.

Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items rg range = - 0.27-0.78), ADHD (items rg range = - 0.40-1), and schizophrenia (items rg range = - 0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs.

Exploring the differentiation of behavioural and emotional problems across childhood: A prospective longitudinal cohort study.

Background: An individual's overall burden of behavioural and emotional problems across childhood is associated with increased likelihood of later mental health conditions. However, the relative extent of behavioural versus emotional problems - that is, the extent to which the domains are differentiated from one another - may provide additional information about who is at risk of developing a mental health condition. Here, we seek to validate differentiation as an independent predictor of later mental health conditions, and to explore its aetiology. Methods: We analysed data from ~79,000 children in the population-based Norwegian Mother, Father, and Child Cohort Study, and linked health-care registries. In preregistered analyses, we modelled the extent and rate of differentiation of behavioural and emotional problems between ages 1.5-5 years, and estimated associations with later symptoms (age 8) and diagnoses (after age 8). We also explored the aetiology of differentiation by estimating associations with early life exposures and, in a subset of 23,945 full siblings, assessing the impact of accounting for unobserved familial confounding. Results: Differentiation of behavioural and emotional problems was associated with later symptoms and diagnoses of mental health conditions, independent of total problems. Maternal at-risk drinking (ß = 0.04 [0.02, 0.06]) and parental relationship problems (ß = 0.04 [0.02, 0.05]) were associated with higher behavioural relative to emotional problems at age 5. Maternal prenatal distress (|ß| = 0.04 [0.03, 0.06]), concurrent distress (|ß| = 0.04 [0.02, 0.06]) and parental education (|ß| = 0.05 [0.04, 0.07]) predicted higher emotional relative to behavioural problems at age 5. Estimates for maternal prenatal distress and at-risk drinking were consistent across both unadjusted and adjusted analyses accounting for unobserved familial risk. Conclusions: Differentiation of behavioural and emotional problems in early childhood represents a valid source of inter-individual variability linked to the later emergence of psychopathology and may be relevant for early detection and prevention strategies for mental health.

The globalizability of temporal discounting.

Economic inequality is associated with preferences for smaller, immediate gains over larger, delayed ones. Such temporal discounting may feed into rising global inequality, yet it is unclear whether it is a function of choice preferences or norms, or rather the absence of sufficient resources for immediate needs. It is also not clear whether these reflect true differences in choice patterns between income groups. We tested temporal discounting and five intertemporal choice anomalies using local currencies and value standards in 61 countries (N = 13,629). Across a diverse sample, we found consistent, robust rates of choice anomalies. Lower-income groups were not significantly different, but economic inequality and broader financial circumstances were clearly correlated with population choice patterns.

RAISE study protocol: a cross-sectional, multilevel, neurobiological study of resilience after individual stress exposure.

INTRODUCTION: This paper describes the protocol for an ongoing project funded by the Royal Society, the Resilience After Individual Stress Exposure (RAISE) study; which aims to examine the factors and mechanisms that facilitate resilient functioning after childhood adversity (CA). METHODS AND ANALYSIS: We aim to recruit up to 200 participants. We will use dimension reduction techniques (principal component analysis) on standard-normally transformed individual parameters of mental health, social functioning and CA to calculate a composite measure of adaptive (ie, 'resilient') psychosocial functioning. To examine the neuroimmune responses to stress and their relationship with the brain and social environment, we will use a well validated functional MRI task; the Montreal imaging stress task and venepuncture. We will run group or dimensional comparisons in multiple levels of biological and psychological outcomes, as well as mediation and moderation analyses to study how key biological systems (ie, the hypothalamic-pituitary-adrenal axis and the immune system) interrelate and interact with brain function and social influences in order to facilitate resilient functioning after CA. We hypothesise that resilient functioning will be facilitated by reduced morning cortisol and cytokine levels before and after the stressor and improved neural responses to such stress, as well as increased gray matter volume in the hippocampus and prefrontal cortex, enhanced inhibitory control and emotion regulation, and more friendship and family support. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by the National Research Ethics Service, NRES Committee East of England-Cambridge Central and external reviewers from the Royal Society (RGF\R1\180064 and RGF\EA\180029). The results of the RAISE study will be disseminated through (1) publications in scientific peer reviewed journals, (2) presentations on relevant scientific conferences and meetings, (3) publications and presentations for the general public and (4) through social media.

Psycho-social factors associated with mental resilience in the Corona lockdown.

The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience (p < 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p < 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

The Resilient Emotional Brain: A Scoping Review of the Medial Prefrontal Cortex and Limbic Structure and Function in Resilient Adults With a History of Childhood Maltreatment.

Childhood maltreatment (CM) is one of the strongest predictors of adult mental illness, although not all adults with CM develop psychopathology. Here, we describe the structure and function of the emotional brain regions that may contribute to resilient functioning after CM. We review studies that report medial prefrontal cortex, amygdala, and hippocampus (limbic regions) structure, function, and/or connections in resilient adults (i.e., those reporting CM without psychopathology) versus vulnerable adults (i.e., those reporting CM with psychopathology) or healthy adults (those without CM and with no psychopathology). We find that resilient adults have larger hippocampal gray and white matter volume and greater connectivity between the central executive network and the limbic regions. In addition, resilient adults have improved ability to regulate emotions through medial prefrontal cortex-limbic downregulation, lower hippocampal activation to emotional faces, and increased amygdala habituation to stress. We highlight the need for longitudinal designs that examine resilient functioning across domains and consider gender, type, timing, and nature of CM assessments and further stressors to further improve our understanding of the role of the emotional brain in resilient functioning after CM.

Positive memory specificity is associated with reduced vulnerability to depression.

Depression is the leading cause of disability worldwide1. Early life stress exposure increases risk for depression2 and has been proposed to sensitize the maturing psychophysiological stress system to stress in later life3. In response to stress, positive memory activation has been found to dampen cortisol responses and improve mood in humans4 and to reduce depression-like behaviour in mice5. We used path modelling to examine whether recalling specific positive memories predicts reduced vulnerability to depression (high morning cortisol6-9 and negative self-cognitions during low mood10-12) in adolescents at risk due to early life stress (n = 427, age 14 years)8. We found that positive memory specificity was associated with lower morning cortisol and fewer negative self-cognitions during low mood over the course of one year. Moderated mediation analyses demonstrated that positive memory specificity was related to lower depressive symptoms through fewer negative self-cognitions in response to negative life events reported in the one-year interval. These findings indicate that recalling specific positive life experiences may be a resilience factor13 that helps in lowering depressive vulnerability in adolescents with a history of early life stress.

Author Correction: Positive memory specificity is associated with reduced vulnerability to depression.

The original and corrected references are shown in the accompanying Author Correction.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

No Differential Effects of Neural and Psychological Explanations of Psychopathy on Moral Behavior.

Research in neurocriminology has explored the link between neural functions and structures and the psychopathic disposition. This online experiment aimed to assess the effect of communicating the neuroscience of psychopathy on the degree to which lay people exhibited attitudes characteristic of psychopathy in particular in terms of moral behavior. If psychopathy is blamed on the brain, people may feel less morally responsible for their own psychopathic tendencies. In the study, participants read false feedback about their own psychopathic traits supposedly inferred from their Facebook likes, described either in neurobiological or cognitive terms. Participants were randomly allocated to read that they either had above-average or below-average psychopathic traits. We found no support for the hypothesis that the neuroscientific explanation of psychopathy influences moral behavior. This casts doubt on the fear that communicating the neuroscience of psychopathy will promote psychopathic attitudes.