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Over 50% of children with a parent with severe mental illness will develop mental illness by early adulthood. However, intergenerational transmission of risk for mental illness in one’s children is insufficiently considered in clinical practice, nor is it sufficiently utilised into diagnostics and care for children of ill parents. This leads to delays in diagnosing young offspring and missed opportunities for protective actions and resilience strengthening. Prior twin, family, and adoption studies suggest that the aetiology of mental illness is governed by a complex interplay of genetic and environmental factors, potentially mediated by changes in epigenetic programming and brain development. However, how these factors ultimately materialise into mental disorders remains unclear. Here, we present the FAMILY consortium, an interdisciplinary, multimodal (e.g., (epi)genetics, neuroimaging, environment, behaviour), multilevel (e.g., individual-level, family-level), and multisite study funded by a European Union Horizon-Staying-Healthy-2021 grant. FAMILY focuses on understanding and prediction of intergenerational transmission of mental illness, using genetically informed causal inference, multimodal normative prediction, and animal modelling. Moreover, FAMILY applies methods from social sciences to map social and ethical consequences of risk prediction to prepare clinical practice for future implementation. FAMILY aims to deliver: (i) new discoveries clarifying the aetiology of mental illness and the process of resilience, thereby providing new targets for prevention and intervention studies; (ii) a risk prediction model within a normative modelling framework to predict who is at risk for developing mental illness; and (iii) insight into social and ethical issues related to risk prediction to inform clinical guidelines.

Background Parent-adolescent interactions, particularly parental criticism and praise, have previously been identified as factors relevant to self-concept development and, when negative, to adolescent depression. Yet, whether adolescents with depression show aberrant emotional and neural reactivity to parental criticism and praise is understudied. Methods Adolescents with depression (n = 20) and healthy controls (n = 59) received feedback supposedly provided by their mother or father in the form of negative ('untrustworthy'), neutral ('chaotic'), and positive ('respectful') personality evaluations while in an MRI-scanner. After each feedback word, adolescents reported their mood. Beforehand, adolescents had rated whether these personality evaluations matched their self-views. Results In both groups, mood decreased after criticism and increased after praise. Adolescents with depression reported blunted mood responses after praise, whereas there were no mood differences after criticism. Neuroimaging analyses revealed that adolescents with depression (v. healthy controls) exhibited increased activity in response to criticism in the subgenual anterior cingulate cortex, temporal pole, hippocampus, and parahippocampal gyrus. Praise consistent with adolescents' self-views improved mood independent of depression status, while criticism matching self-views resulted in smaller mood increases in adolescents with depression (v. healthy controls). Exploratory analyses indicated that adolescents with depression recalled criticism (v. praise) more. Conclusions Adolescents with depression might be especially attentive to parental criticism, as indexed by increased sgACC and hippocampus activity, and memorize this criticism more. Together with lower positive impact of praise, these findings suggest that cognitive biases in adolescent depression may affect how parental feedback is processed, and may be fed into their self-views.

Eye contact improves mood, facilitates connectedness, and is assumed to strengthen the parent–child bond. Adolescent depression is linked to difficulties in social interactions, the parent–child bond included. Our goal was to elucidate adolescents’ affective and neural responses to prolonged eye contact with one’s parent in nondepressed adolescents (HC) and how these responses are affected in depressed adolescents. While in the scanner, 59 nondepressed and 19 depressed adolescents were asked to make eye contact with their parent, an unfamiliar peer, an unfamiliar adult, and themselves by using videos of prolonged direct and averted gaze, as an approximation of eye contact. After each trial, adolescents reported on their mood and feelings of connectedness, and eye movements and BOLD-responses were assessed. In HCs, eye contact boosted mood and feelings of connectedness and increased activity in inferior frontal gyrus (IFG), temporal pole, and superior frontal gyrus. Unlike HCs, eye contact did not boost the mood of depressed adolescents. While HCs reported increased mood and feelings of connectedness to the sight of their parent versus others, depressed adolescents did not. Depressed adolescents exhibited blunted overall IFG activity. These findings show that adolescents are particularly sensitive to eye contact and respond strongly to the sight of their parents. This sensitivity seems to be blunted in depressed adolescents. For clinical purposes, it is important to gain a better understanding of how the responsivity to eye contact in general and with their parents in particular, can be restored in adolescents with depression.

Objectives: The current study aimed to examine: (1.1) causal beliefs about adolescent depression in a sample of adolescents with a clinical depression and their mothers and fathers; (1.2) within-family overlap of causal beliefs; (2.1) mothers' and fathers' reflected causal beliefs about their child's perspective; (2.2) the accuracy of mothers' and fathers' reflected causal beliefs as related to their child's causal beliefs. Design: Qualitative study using a within-family approach. Methods: Adolescents with a current clinical depression (MDD/dysthymia; N = 34) and their parents (N = 34 mothers, N = 26 fathers) were independently interviewed about their causal beliefs about the adolescents' depression. Parents were additionally interviewed about their perception of their child's causal beliefs (i.e., reflected causal beliefs). Results: The causal beliefs most frequently mentioned by adolescents, mothers and fathers are: characteristics of the child, social factors, school and various stressful experiences. Parent–child overlap was relatively low, specifically for the themes of bewilderment, cumulative effect and stressful life events, whereas overlap was relatively high for themes of social factors, school and stressful experiences outside of the family. Parents were relatively accurate in their reflected causal beliefs, but tended to underestimate their child's insights into possible causes of their depression. Accuracy of parents' reflected causal beliefs was particularly low for the theme cumulative effect and high for social factors. Conclusions: The various causal beliefs of adolescents and their parents could be used in therapeutic setting. Future research could examine whether (guided) conversations may promote alignment within families and treatment efficacy.

Adolescence is a time period characterized by extremes in affect and increasing prevalence of mental health problems. Prior studies have illustrated how affect states of adolescents are related to interactions with parents. However, it remains unclear how affect states among family triads, that is adolescents and their parents, are related in daily life. This study investigated affect state dynamics (happy, sad, relaxed, and irritated) of 60 family triads, including 60 adolescents (Mage = 15.92, 63.3% females), fathers and mothers (Mage = 49.16). The families participated in the RE-PAIR study, where they reported their affect states in four ecological momentary assessments per day for 14 days. First, we used multilevel vector-autoregressive network models to estimate affect dynamics across all families, and for each family individually. Resulting models elucidated how family affect states were related at the same moment, and over time. We identified relations from parents to adolescents and vice versa, while considering family variation in these relations. Second, we evaluated the statistical performance of the network model via a simulation study, varying the percentage missing data, the number of families, and the number of time points. We conclude with substantive and statistical recommendations for future research on family affect dynamics.

One of the most prevalent nonverbal, social phenomena known to automatically elicit self- and other-referential processes is eye contact. By its negative effects on the perception of social safety and views about the self and others, childhood emotional maltreatment (CEM) may fundamentally affect these processes. To investigate whether the socioaffective consequences of CEM may become visible in response to (prolonged) eye gaze, 79 adult participants (mean [M] age = 49.87, standard deviation [SD] age = 4.62) viewed videos with direct and averted gaze of an unfamiliar other and themselves while we recorded self-reported mood, eye movements using eye-tracking, and markers of neural activity using fMRI. Participants who reported higher levels of CEM exhibited increased activity in ventromedial prefrontal cortex to one’s own, but not to others’, direct gaze. Furthermore, in contrast to those who reported fewer of such experiences, they did not report a better mood in response to a direct gaze of self and others, despite equivalent amounts of time spent looking into their own and other peoples’ eyes. The fact that CEM is associated with enhanced neural activation in a brain area that is crucially involved in self-referential processing (i.e., vmPFC) in response to one’s own direct gaze is in line with the chronic negative impact of CEM on a person’s self-views. Interventions that directly focus on targeting maladaptive self-views elicited during eye gaze to self may be clinically useful.