The Mood and Resilience in Offspring (MARIO) project: a longitudinal cohort study among offspring of parents with and without a mood disorder.

BACKGROUND: One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. METHODS: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected. DISCUSSION: The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.

Behavioral inhibition, negative parenting, and social withdrawal: Longitudinal associations with loneliness during early, middle, and late adolescence.

Adolescent loneliness can have detrimental effects on physical and mental health, but there is limited understanding of its antecedents in infancy and childhood. A 20-year longitudinal, multi-informant, and multi-methods study (first data collection in 1998) was conducted to examine mechanisms underlying adolescent loneliness (N = 128, 52% boys, Mage_baseline  = 1.23, SD = 0.02, 99% White, recruitment in Dutch urban, healthcare centers). Structural equation modeling showed that high infant behavioral inhibition (BI) was indirectly associated with high loneliness during adolescence via high childhood social withdrawal. This indirect effect was equally strong during early, middle, and late adolescence. Contrary to expectations, infant parenting did not moderate the relation between BI and social withdrawal. The results suggest a developmental cascade with infant BI showing long-lasting indirect effects on adolescent loneliness up to 20 years later via childhood social withdrawal.

Interplay between genetic risk and the parent environment in adolescence and substance use in young adulthood: A TRAILS study.

Many adolescents start using tobacco, alcohol, and cannabis. Genetic vulnerability, parent characteristics in young adolescence, and interaction (GxE) and correlation (rGE) between these factors could contribute to the development of substance use. Using prospective data from the TRacking Adolescent Individuals' Lives Survey (TRAILS; N = 1,645), we model latent parent characteristics in young adolescence to predict young adult substance use. Polygenic scores (PGS) are created based on genome-wide association studies (GWAS) for smoking, alcohol use, and cannabis use. Using structural equation modeling we model the direct, GxE, and rGE effects of parent factors and PGS on young adult smoking, alcohol use, and cannabis initiation. The PGS, parental involvement, parental substance use, and parent-child relationship quality predicted smoking. There was GxE such that the PGS amplified the effect of parental substance use on smoking. There was rGE between all parent factors and the smoking PGS. Alcohol use was not predicted by genetic or parent factors, nor by interplay. Cannabis initiation was predicted by the PGS and parental substance use, but there was no GxE or rGE. Genetic risk and parent factors are important predictors of substance use and show GxE and rGE in smoking. These findings can act as a starting point for identifying people at risk.

Weighing psychosocial factors in relatives for the risk of psychopathology: a study of patients with depressive and anxiety disorders and their siblings.

PURPOSE: Siblings of probands with depressive and anxiety disorders are at increased risk for psychopathology, but little is known about how risk factors operate within families to increase psychopathology for siblings. We examined the additional impact of psychosocial risk factors in probands-on top of or in combination with those in siblings-on depressive/anxious psychopathology in siblings. METHODS: The sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and their sibling(s) (N = 380 proband-sibling pairs). Sixteen psychosocial risk factors were tested. In siblings, depressive and anxiety disorders were determined with standardized psychiatric interviews; symptom severity was measured using self-report questionnaires. Analyses were performed with mixed-effects models accounting for familial structure. RESULTS: In siblings, various psychosocial risk factors (female gender, low income, childhood trauma, poor parental bonding, being single, smoking, hazardous alcohol use) were associated with higher symptomatology and likelihood of disorder. The presence of the same risk factor in probands was independently associated (low income, being single) with higher symptomatology in siblings or moderated (low education, childhood trauma, hazardous alcohol use)-by reducing its strength-the association between the risk factor and symptomatology in siblings. There was no additional impact of risk factors in probands on likelihood of disorder in siblings. CONCLUSION: Our findings demonstrate the importance of weighing psychosocial risk factors within a family context, as it may provide relevant information on the risk of affective psychopathology for individuals.

Familial risk for depressive and anxiety disorders: associations with genetic, clinical, and psychosocial vulnerabilities.

BACKGROUND: In research and clinical practice, familial risk for depression and anxiety is often constructed as a simple Yes/No dichotomous family history (FH) indicator. However, this measure may not fully capture the liability to these conditions. This study investigated whether a continuous familial loading score (FLS), incorporating family- and disorder-specific characteristics (e.g. family size, prevalence of depression/anxiety), (i) is associated with a polygenic risk score (PRS) for major depression and with clinical/psychosocial vulnerabilities and (ii) still captures variation in clinical/psychosocial vulnerabilities after information on FH has been taken into account. METHODS: Data came from 1425 participants with lifetime depression and/or anxiety from the Netherlands Study of Depression and Anxiety. The Family Tree Inventory was used to determine FLS/FH indicators for depression and/or anxiety. RESULTS: Persons with higher FLS had higher PRS for major depression, more severe depression and anxiety symptoms, higher disease burden, younger age of onset, and more neuroticism, rumination, and childhood trauma. Among these variables, FH was not associated with PRS, severity of symptoms, and neuroticism. After regression out the effect of FH from the FLS, the resulting residualized measure of FLS was still associated with severity of symptoms of depression and anxiety, rumination, and childhood trauma. CONCLUSIONS: Familial risk for depression and anxiety deserves clinical attention due to its associated genetic vulnerability and more unfavorable disease profile, and seems to be better captured by a continuous score that incorporates family- and disorder-specific characteristics than by a dichotomous FH measure.

Prosocial Behavior and Aggression in the Daily School Lives of Early Adolescents.

Research has not adequately addressed a possible mutual co-regulatory influence of prosocial and aggressive behaviors in adolescents' daily lives. This study explored bidirectional within-person associations between prosocial and aggressive behaviors in the daily school lives of early adolescents. The sample included 242 sixth-graders [Mage = 11.96 (SD = 0.18), 50% girls] and their teachers. Adolescents reported on daily prosocial behavior and reactive and proactive aggression for ten consecutive days. Teachers and adolescents reported on adolescents' overall prosocial behaviors. Across-day prosocial behaviors increased after days when adolescents exhibited more reactive aggression but not among self-reported low-prosocial adolescents. Increased prosocial behaviors did not mitigate aggression the next day. The findings suggest prosocial behaviors are a plausible compensatory strategy after daily aggressive reactions.

It is a family affair: individual experiences and sibling exposure to emotional, physical and sexual abuse and the impact on adult depressive symptoms.

BACKGROUND: Childhood abuse and neglect often occurs within families and can have a large influence on mental well-being across the lifespan. However, the sibling concordance of emotional abuse and neglect (i.e. together referred to as emotional maltreatment; EM), physical abuse (PA) and sexual abuse (SA) and the long-term impact on the context of siblings' maltreatment experiences are unclear. To examine the influence of EM, PA and SA on adult depressive symptoms within the family framework we differentiate between (a) the family-wide (mean level of all siblings) effects and (b) the individual deviation from the mean family level of maltreatment. METHODS: The sample (N = 636) consists of 256 families, including at least one lifetime depressed or anxious individual and their siblings. Multilevel modeling was used to examine the family-wide and relative individual effects of childhood maltreatment (CM). RESULTS: (a) Siblings showed most similarity in their reports of EM followed by PA. SA was mostly reported by one person within a family. In line with these observations, the mean family levels of EM and PA, but not SA, were associated with more depressive symptoms. In addition, (b) depression levels were more elevated in individuals reporting more EM than the family mean. CONCLUSIONS: Particularly in the case of more visible forms of CM, siblings' experiences of EM and PA are associated with the elevated levels of adult depressive symptoms. Findings implicate that in addition to individual maltreatment experiences, the context of siblings' experiences is another crucial risk factor for an individuals' adult depressive symptomatology.

Prevention programmes for children of parents with a mood/anxiety disorder: Systematic review of existing programmes and meta-analysis of their efficacy.

OBJECTIVES: To systematically describe the characteristics and techniques of prevention programmes for children of parents with mood/anxiety disorders. In addition, recruitment approaches and difficulties were identified and a meta-analysis was conducted to examine the efficacy of these prevention programmes. METHODS: Randomized controlled trials assessing the efficacy of a prevention programme for children (6-25 years) of parents with mood and/or anxiety disorders were included. A systematic literature search was conducted in PubMed, PsychINFO, and CENTRAL from the earliest record to March 2019. In addition, programme manuals of identified prevention programmes were requested for a content analysis. RESULTS: Twenty-two articles containing eight unique prevention programmes involving 1,325 subjects were identified. Programmes varied in the number and types of techniques, but all provided psychoeducation. Results suggested that recruitment via clinicians was more successful than recruitment via health maintenance organization databases. In a meta-analysis, a significant risk difference was found in favour of prevention programmes on the risk of developing a depressive/anxiety disorder in offspring at short-term (9-18 months follow-up; RR = 0.37, 95% CI [0.21; 0.66]) and long-term follow-up (24 months or longer follow-up; RR = 0.71, 95% CI [0.57; 0.87] and on symptom levels in offspring at post-intervention (SMD = -0.19, 95% CI [-0.36; -0.02]) and at 12-months follow-up (SMD = -0.31, 95% CI [-0.57; -0.06]). CONCLUSIONS: The prevention programmes combined psychoeducational elements with skills training and/or cognitive-behavioural therapy elements. The recruitment process and the content of these programmes are sometimes insufficiently described. Nevertheless, they appear to be effective, indicating a need to further examine how these programmes exactly work and for whom. PRACTITIONER POINTS: Preventive interventions for children of parents with mood/anxiety disorders appear to be effective in preventing these disorders in offspring. Available preventive intervention programmes focus mostly on psychoeducation, cognitive-behavioural therapy, and family processes. More effort should be made into describing preventive interventions so that they can be easily implemented by practitioners. Studies should further examine why and for whom preventive interventions for children of parents with mood/anxiety disorders are effective.

Grumpy or depressed? Disentangling typically developing adolescent mood from prodromal depression using experience sampling methods.

INTRODUCTION: This study aimed at differentiating normative developmental turmoil from prodromal depressive symptoms in adolescence. METHOD: Negative and positive mood (daily) in different contexts (friends, home, school), and (subsequent) depressive symptoms were assessed in Dutch adolescents. RESULTS & CONCLUSION: Mixture modeling on one cross-sectional study, using a newly developed questionnaire (CSEQ; subsample 1a; n = 571; girls 55.9%; Mage = 14.17) and two longitudinal datasets with Experience Sampling Methods data (subsample 1b: n = 241; Mage = 13.81; 62.2% girls, sample 2: n = 286; 59.7% girls; Mage = 14.19) revealed three mood profiles: 18-24% "happy", 43-53% "typically developing", and 27-38% "at-risk". Of the "at-risk" profile between 12.5% and 25% of the adolescents scored above the clinical cut-off for depression. These mood profiles predicted later depressive symptoms, while controlling for earlier symptoms. In subsample 1b, parents were not always aware of the mental health status of their adolescent.

Human responses to Covid-19: The role of optimism bias, perceived severity, and anxiety.

During the Covid-19 pandemic, the governments are trying to contain the spread with non-pharmaceutical interventions (NPIs), such as social distancing rules, restrictions, and lockdowns. In an effort to identify factors that may influence population adherence to NPIs, we examined the role of optimism bias, anxiety, and perceived severity of the situation in relation to engagement in protective behavioral changes and satisfaction with governments' response to this pandemic. We conducted an online survey in 935 participants (M age  = 34.29; 68.88% females) that was disseminated in April and May 2020 in the Netherlands, Germany, Greece, and USA. Individuals with high optimism bias engaged less in behavioral changes, whereas individuals with high levels of anxiety and high perceived severity engaged more in behavioral changes. Individuals with high optimism bias and high levels of anxiety were less satisfied with the governments' response, albeit for different reasons. Individuals who reported low perceived severity and low government satisfaction engaged the least in behavioral changes, whereas participants who reported high perceived severity and low government satisfaction engaged the most in behavioral changes. This study contributes to a better understanding of the psychological factors that influence people's responses to NPIs.

Neural Cognitive Control Moderates the Relation between Negative Life Events and Depressive Symptoms in Adolescents.

The present longitudinal study examined the role of neural cognitive control in the relation between negative and positive life events and depressive symptoms in adolescents. The sample comprised 138 adolescents (52% male, Mage = 13.49 at baseline) and their parents. At Time 1, adolescents participated in a functional neuroimaging session in which neural cognitive control was measured as hemodynamic activity during an inhibitory control task, and parents reported on adolescents' positive and negative life events within the past year. Adolescents and parents reported on adolescent depressive symptoms at Time 1, Time 2 (1 year later), and Time 3 (2 years later). Conditional latent growth curve model was used to test the main and interaction effects of neural cognitive control and positive/negative life events on the growth factors of depressive symptoms. Higher neural cognitive control moderated the relation between negative life events and the intercept of depressive symptoms. Adolescents with higher neural cognitive control did not experience higher depressive symptoms when confronted with more negative life events, whereas their counterparts with lower neural cognitive control did. The interaction effect between neural cognitive control and positive life events on depressive symptoms was not significant. Results suggest that neural cognitive control acts as a protective factor such that adolescents with higher neural cognitive control are protected against depressionogenic effects of negative life events, whereas adolescents with lower cognitive control are at greater risk for depressive symptoms in response to negative life events.

Intergenerational transmission of delay discounting: The mediating role of household chaos.

INTRODUCTION: Adolescence is a period when impulsive decision making may be especially vulnerable to environmental influences. Impulsive decision making is often assessed using a delay discounting paradigm, which measures the preference for smaller rewards sooner over larger rewards with a delay. Research is needed to clarify the relationship between parents' and adolescents' delay discounting and to identify related environmental processes that might facilitate the intergenerational transmission of delay discounting. The current prospective longitudinal study examined the competing mediating processes of household chaos and harsh parenting in the intergenerational transmission of delay discounting between parents and adolescents. METHODS: Participants included 167 adolescents (mean age = 14.07 years at Time 1; 53% male) and their parents (mean age = 41.98 years at Time 1; 87% female) recruited from the southeast United States. Parents' delay discounting was collected at Time 1, and adolescents' delay discounting was collected both at Time 1 and at Time 3 via a computerized delay discounting task. Parents and adolescents reported household chaos and harsh parenting at Time 2. RESULTS: A parallel mediation model indicated that parents' delay discounting at Time 1 indirectly predicted adolescents' delay discounting Time 3 residualized change scores (regressing Time 3 delay discounting onto baseline delay discounting) through household chaos but not through harsh parenting at Time 2. CONCLUSIONS: These results underline the importance of household chaos in facilitating the intergenerational transmission of delay discounting between parents and adolescents. Furthermore, our findings point to household chaos as a potential environmental target for interrupting intergenerational impulsivity.

Oxytocin Receptor Gene (OXTR) and Deviant Peer Affiliation: A Gene-Environment Interaction in Adolescent Antisocial Behavior.

Although the oxytocin receptor gene (OXTR) is involved in aggression and social affiliation, it has not been examined in gene-environment interaction studies. This longitudinal study examined the effect of genetic variants in OXTR and its gene-environment interaction with perceived deviant peer affiliation in the trajectories of antisocial behavior in 323 adolescents (182 males) from 13 to 18 years. Annual assessments of reactive and proactive aggression, delinquency, and friends' delinquency, as well as DNA at age 17 were collected. Gene-based tests yielded no main effect of OXTR, but revealed a significant gene-environment interaction in proactive aggression and delinquency. Variation in the OXTR might affect the influence of deviant peer affiliation on antisocial behavior, contributing to a better understanding of individual differences in antisocial behavior.

Neural Correlates of Risk Processing Among Adolescents: Influences of Parental Monitoring and Household Chaos.

Adolescent risky behavior is related to developmental changes in decision-making processes and their neural correlates. Yet, research investigating how the family environment relates to risk processing in the adolescent brain is limited. In this study, longitudinal data were collected from 167 adolescents (13-15 years, 53% male) who self-reported household chaos and their parent's monitoring practices, and completed a decision-making task during functional MRI at Time 1 and Time 2 (1 year apart). Parental knowledge was positively related to insular risk processing only among adolescents in low-chaos environments at both time points. Results highlight environmental correlates of insular risk processing in the developing brain.

Positive and Negative Affect and Adolescent Adjustment: Moderation Effects of Prefrontal Functioning.

We examined whether cognitive control moderates the effects of emotion on adolescent internalizing and externalizing symptomatology in a longitudinal study of 138 adolescents. Self-reported positive affect (PA) and negative affect and behavioral and neural indicators of cognitive control, indexed by performance and prefrontal hemodynamic response during a cognitive interference task, were collected at Time 1. Self-reported internalizing and externalizing symptomatology were collected at Time 1 and Time 2 (1 year later). Results indicated that higher PA predicted decreases in externalizing symptomatology, but only for adolescents with poor neural cognitive control. No moderation effects were found for behavioral cognitive control. Findings imply the beneficial effects of PA on the development of externalizing problems among adolescents with poor prefrontal functioning.

The Association of Genetic Predisposition to Depressive Symptoms with Non-suicidal and Suicidal Self-Injuries.

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age = 42.4 years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p = 0.008, explained variance ranging from 0.10 to 0.16 %) and, less consistently, in suicide attempts (lowest p = 0.04, explained variance ranging from 0.12 to 0.23 %). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI.

A 5-Year Longitudinal Study on Mood Variability Across Adolescence Using Daily Diaries.

This study explored the development of mood variability in 474 Dutch adolescents (56.8% male, 90.1% medium to high socioeconomic status) from a community sample, followed from ages 13 to 18 years. Three times per year, adolescents reported on daily happiness, anger, sadness, and anxiety for 5 days using Internet diaries (15 assessment weeks; from 2006 to 2010). Mood variability scores were calculated as means of absolute differences between consecutive days. Results showed that happiness, anger, and sadness variability continuously declined across adolescence, while anxiety variability increased initially, then decreased, and then increased toward late adolescence. Despite females experiencing higher happiness and sadness variability, the rate of change across adolescence was similar for both sexes. Implications for normative emotional development and future studies are discussed.

A theory-informed emotion regulation variability index: Bray-Curtis dissimilarity.

Emotion regulation (ER) variability refers to how individuals vary their use of ER strategies across time. It helps individuals to meet contextual needs, underscoring its importance in well-being. The theoretical foundation of ER variability recognizes two constituent processes: strategy switching (e.g., moving from distraction to social sharing) and endorsement change (e.g., decreasing the intensity of both distraction and social sharing). ER variability is commonly operationalized as the SD between strategies per observation (between-strategy SD) or within a strategy across time (within-strategy SD). In this article, we show that these SD-based approaches cannot sufficiently capture strategy switching and endorsement change, leading to ER variability indices with poor validity. We propose Bray-Curtis dissimilarity, a measure used in ecology to quantify biodiversity variability, as a theory-informed ER variability index. First, we demonstrate how Bray-Curtis dissimilarity is more sensitive than SD-based approaches in detecting ER variability through two simulation studies. Second, assuming that higher ER variability is adaptive in daily life, we test the relation between ER variability and negative affect in three experience sampling method data sets (total N = [70, 95, 200], number of moment-level observations = [5,040, 6,329, 14,098]). At both the moment level and person level, higher Bray-Curtis dissimilarity predicted lower negative affect more consistently than SD-based indices. We conclude that Bray-Curtis dissimilarity may better capture moment-level within-person ER variability and could have implications for studying variability in other multivariate dynamic processes. The article is accompanied by an R tutorial and practical recommendations for using Bray-Curtis dissimilarity with experience sampling method data. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Risk-related brain activation is linked to longitudinal changes in adolescent health risk behaviors.

Middle adolescence is the period of development during which youth begin to engage in health risk behaviors such as delinquent behavior and substance use. A promising mechanism for guiding adolescents away from risky choices is the extent to which adolescents are sensitive to the likelihood of receiving valued outcomes. Few studies have examined longitudinal change in adolescent risky decision making and its neural correlates. To this end, the present longitudinal three-wave study (Nw1 = 157, Mw1= 13.50 years; Nw2 = 148, Mw2= 14.52 years; Nw3 = 143, Mw3= 15.55 years) investigated the ontogeny of mid-adolescent behavioral and neural risk sensitivity, and their baseline relations to longitudinal self-reported health risk behaviors. Results showed that adolescents became more sensitive to risk both in behavior and the brain during middle adolescence. Across three years, we observed lower risk-taking and greater risk-related activation in the bilateral insular cortex. When examining how baseline levels of risk sensitivity were related to longitudinal changes in real-life health risk behaviors, we found that Wave 1 insular activity was related to increases in self-reported health risk behaviors over the three years. This research highlights the normative maturation of risk-related processes at the behavioral and neural levels during mid-adolescence.

Weighing poor immunometabolic health in relatives for severity of affective symptoms: A study of patients with depressive and anxiety disorders and their siblings.

BACKGROUND: Affective (i.e. depressive and anxiety) disorders often co-occur with immunometabolic diseases and related biological pathways. Although many large population-based and meta-analytic studies have confirmed this link in community and clinical samples, studies in at-risk samples of siblings of persons with affective disorders are lacking. Furthermore, this somatic-mental co-occurrence may be partially explained by familial clustering of the conditions. First, we examined whether the association between a wide range of immunometabolic diseases and related biomarker based risk-profiles with psychological symptoms replicates in at-risk siblings of probands with affective disorders. Second, leveraging on a sibling-pair design, we disentangled and quantified the effect of probands' immunometabolic health on siblings' psychological symptoms and on the association between immunometabolic health and these symptoms in siblings. METHODS: The sample included 636 participants (Mage = 49.7; 62.4% female) from 256 families, each including a proband with lifetime depressive and/or anxiety disorders and at least one of their sibling(s) (N = 380 proband-sibling pairs). Immunometabolic health included cardiometabolic and inflammatory diseases, body mass index (BMI), and composite metabolic (based on the five metabolic syndrome components) and inflammatory (based on interleukin-6 and C-reactive protein) biomarker indices. Overall affective symptoms and specific atypical, energy-related depressive symptoms were derived from self-report questionnaires. Mixed-effects analyses were used to model familial clustering. RESULTS: In siblings, inflammatory disease (γ = 0.25, p = 0.013), higher BMI (γ = 0.10, p = 0.033) and metabolic index (γ = 0.28, p < 0.001) were associated with higher affective symptoms, with stronger associations for atypical, energy-related depressive symptoms (additionally associated with cardiometabolic disease; γ = 0.56, p = 0.048). Immunometabolic health in probands was not independently associated with psychological symptoms in siblings nor did it moderate the association between immunometabolic health and psychological symptoms estimated in siblings. CONCLUSIONS: Our findings demonstrate that the link between later life immunometabolic health and psychological symptoms is consistently present also in adult siblings at high risk for affective disorders. Familial clustering did not appear to have a substantial impact on this association. Instead, individual lifestyle, rather than familial factors, may have a relatively higher impact in the clustering of later life immunometabolic conditions with psychological symptoms in at-risk adult individuals. Furthermore, results highlighted the importance of focusing on specific depression profiles when investigating the overlap with immunometabolic health.