Relationships between Depression and Executive Functioning in Adolescents: The Moderating Role of Unpredictable Home Environment

Gillespie, Marie L.; Rao, Uma

doi:10.1007/s10826-022-02296-z

Cited by 13 publications

(8 citation statements)

References 84 publications

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“…Building upon these findings, the QUIC has now also been linked to posttraumatic stress, anhedonic, depressive and anxiety symptoms as well as suicidal ideation in trauma-exposed male veterans ( Spadoni et al, 2022 ). Further, Gillespie and Rao (2022) recently documented associations between increased childhood unpredictability assessed with the QUIC with higher rates of depressive symptoms and compromised executive function in adolescents. Thus, increasing evidence suggests that childhood unpredictability is a distinct dimension of early life adversity that deserves additional consideration and that the QUIC is a valid tool to further these investigations.…”

Section: Introductionmentioning

confidence: 99%

Exposure to unpredictability and mental health: Validation of the brief version of the Questionnaire of Unpredictability in Childhood (QUIC-5) in English and Spanish

et al. 2022

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Unpredictability is increasingly recognized as a primary dimension of early life adversity affecting lifespan mental health trajectories; screening for these experiences is therefore vital. The Questionnaire of Unpredictability in Childhood (QUIC) is a 38-item tool that measures unpredictability in childhood in social, emotional and physical domains. The available evidence indicates that exposure to unpredictable experiences measured with the QUIC predicts internalizing symptoms including depression and anxiety. The purpose of the present study was to validate English and Spanish brief versions (QUIC-5) suitable for administration in time-limited settings (e.g., clinical care settings, large-scale epidemiological studies). Five representative items were identified from the QUIC and their psychometric properties examined. The predictive validity of the QUIC-5 was then compared to the QUIC by examining mental health in four cohorts: (1) English-speaking adult women assessed at 6-months postpartum (N = 116), (2) English-speaking male veterans (N = 95), (3) English-speaking male and female adolescents (N = 155), and (4) Spanish-speaking male and female adults (N = 285). The QUIC-5 demonstrated substantial variance in distributions in each of the cohorts and is correlated on average 0.84 (r’s = 0.81–0.87) with the full 38-item version. Furthermore, the QUIC-5 predicted internalizing symptoms (anxiety and depression) in all cohorts with similar effect sizes (r’s = 0.16–0.39; all p’s < 0.05) to the full versions (r’s = 0.19–0.42; all p’s < 0.05). In sum, the QUIC-5 exhibits good psychometric properties and is a valid alternative to the full QUIC. These findings support the future use of the QUIC-5 in clinical and research settings as a concise way to measure unpredictability, identify risk of psychopathology, and intervene accordingly.

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Section: Introductionmentioning

confidence: 99%

Exposure to unpredictability and mental health: Validation of the brief version of the Questionnaire of Unpredictability in Childhood (QUIC-5) in English and Spanish

et al. 2022

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“…In addition to poverty (assessed as income-toneeds ratio), and maternal depressive symptoms and sensitivity, we tested the role of unpredictable signals from the mother/caretaker and the household environment. This dimension of adversity has emerged in our work (37,(39)(40)(41)(43)(44)(45)47,126,127) and independently, in work by others (42,(128)(129)(130) as a contributor to cognitive outcomes including effortful control (39)(40)(41)131) and emotional (41,44,127,130,132) outcomes in children, adolescents and adults. The neurobiological basis for the detrimental effects of unpredictable environmental signals on brain development are not fully understood.…”

Section: Discussionmentioning

confidence: 80%

Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome

Short,

Weber,

Kamei

et al. 2023

Preprint

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BackgroundAdverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of the world’s children. Whereas the impact of ELA on cognitive and emotional health throughout the lifespan is well-established, it is not clear how distinct types of ELA influence child development, and there are no tools to predict for an individual child their vulnerability or resilience to the consequences of ELAs. Epigenetic markers including DNA-methylation profiles of peripheral cells may encode ELA and provide a predictive outcome marker. However, the rapid dynamic changes in DNA methylation in childhood and the inter-individual variance of the human genome pose barriers to identifying profiles predicting outcomes of ELA exposure. Here, we examined the relation of several dimensions of ELA to changes of DNA methylation, using a longitudinal within-subject design and a high threshold for methylation changes in the hope of mitigating the above challenges.MethodsWe analyzed DNA methylation in buccal swab samples collected twice for each of 110 infants: neonatally and at 12 months. We identified CpGs differentially methylated across time, calculated methylation changes for each child, and determined whether several indicators of ELA associated with changes of DNA methylation for individual infants. We then correlated select dimensions of ELA with methylation changes as well as with measures of executive function at age 5 years. We examined for sex differences, and derived a sex-dependent ‘impact score’ based on sites that most contributed to the methylation changes.FindingsSetting a high threshold for methylation changes, we discovered that changes in methylation between two samples of an individual child reflected age-related trends towards augmented methylation, and also correlated with executive function years later. Among the tested factors and ELA dimensions, including income to needs ratios, maternal sensitivity, body mass index and sex, unpredictability of parental and household signals was the strongest predictor of executive function. In girls, an interaction was observed between a measure of high early-life unpredictability and methylation changes, in presaging executive function.InterpretationThese findings establish longitudinal, within-subject changes in methylation profiles as a signature of some types of ELA in an individual child. Notably, such changes are detectable beyond the age-associated DNA methylation dynamics. Future studies are required to determine if the methylation profile changes identified here provide a predictive marker of vulnerabilities to poorer cognitive and emotional outcomes.FundingSupported by NIH P50 MH096889, a Precision Medicine Initiative grant from the State of California (OPR20141) and the Bren Foundation.Research in contextEvidence before this studyIdentification of individuals at risk for cognitive and emotional problems is required for targeted interventions. At the population level, experiencing early-life adversity has been consistently linked to an elevated susceptibility to various mental illnesses. However, recent studies have revealed a significant limitation in the ability of early-life adversity to predict individual-level risk, and there is presently no reliable tool available to determine whether a child experiencing adversity will develop future mental health problems. Promising efforts to discover predictive markers by examining DNA methylation in peripheral cells are challenged by extensive genetic and epigenetic population variability and the rapid methylation changes taking place during childhood, rendering the identification of clinically valuable predictive markers a complex endeavor.Added value of this studyThis study examined neurodevelopmental outcomes following several dimensions of ELA, including a recently identified dimension-unpredictability of parental and environmental signals to the child. It demonstrates changes in DNA methylation in children exposed to a spectrum of ELA dimensions and severity using alternative approaches to those used previously: It employs a longitudinal within-subject design, enabling assessment of DNA changes within an individual over time rather than a cross section comparison of different groups, and focuses on the first year of life, an understudied epoch of development. The study uses reduced representation bisulfite sequencing to measure methylation, an approach compromising between targeted sequencing and a whole genome approach, and sets a high threshold for methylation changes, in consideration of the large changes of DNA methylation during childhood. Finally, in accord with emerging discoveries of the differential effects of ELA on males and females, the study uncovers sex-effects arising already before puberty.Implications of all the available evidenceCollectively, our study, together with a robust existing literature (1) identifies early-life unpredictability as an additional determinant of DNA methylation changes, (2) indicates that within-subject changes in methylation profiles of peripheral cells hold promise as precision medicine tools for predicting risk and resilience to the adverse consequences of early-life hardships on mental health, and (3) suggests that sex-differences should be explored even prior to puberty. Our study contributes significantly to the important goal of early identification of predictive “epigenetic scars” caused by adverse early-life experiences. Such markers are required for targeting interventions to those most at need.

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“…These observations have important implications as poor effortful control is a transdiagnostic risk factor for psychopathology, including risk for both internalizing and externalizing disorders (Beauchaine & Thayer, 2015; Joseph, McKone, Molina, & Shaw, 2021; Nigg, 2017; Santens et al., 2020) as well as poor physical health and decreased productivity and material success across the lifespan (Johnson, Voegtline, Ialongo, Hill, & Musci, 2022; Moffitt et al., 2011). Intriguingly, a handful of findings indicate that although exposures to unpredictability predict reduced effortful/inhibitory control, cognitive flexibility may be spared, or even enhanced following these exposures (Fields et al., 2021; Gillespie & Rao, 2022; Mittal, Griskevicius, Simpson, Sung, & Young, 2015; Rinne et al., 2022). The possibility that unpredictability affects executive function in targeted ways (by preserving or enhancing cognitive flexibility while impairing inhibitory/effortful control) is consistent with conceptual models emphasizing the role of ELA in shaping both risk and resilience in cognitive phenotypes and represents an important direction for future investigation (Belsky, Schlomer, & Ellis, 2012; Ellis & Del Giudice, 2019; Frankenhuis, Panchanathan, & Nettle, 2016; Munakata, Placido, & Zhuang, 2023; Mushtaq, Bland, & Schaefer, 2011).…”

Section: Cross‐cutting Themes and Future Directionsmentioning

confidence: 99%

“…Two more recent studies have investigated mental health and unpredictability assessed via the QUIC in the context of clinical populations. Gillespie and Rao (2022) examined the association between QUIC and depressive symptoms in adolescents, half of whom had a clinical diagnosis of major depressive disorder. Consistent with expectations, adolescents exposed to higher levels of unpredictability exhibited greater depression symptom severity.…”

Section: Unpredictable Parental Mood Signalsmentioning

confidence: 99%

Annual Research Review: The power of predictability – patterns of signals in early life shape neurodevelopment and mental health trajectories

Davis,

Glynn

2024

Child Psychology Psychiatry

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The global burden of early life adversity (ELA) is profound. The World Health Organization has estimated that ELA accounts for almost 30% of all psychiatric cases. Yet, our ability to identify which individuals exposed to ELA will develop mental illness remains poor and there is a critical need to identify underlying pathways and mechanisms. This review proposes unpredictability as an understudied aspect of ELA that is tractable and presents a conceptual model that includes biologically plausible mechanistic pathways by which unpredictability impacts the developing brain. The model is supported by a synthesis of published and new data illustrating the significant impacts of patterns of signals on child development. We begin with an overview of the existing unpredictability literature, which has focused primarily on longer patterns of unpredictability (e.g. years, months, and days). We then describe our work testing the impact of patterns of parental signals on a moment‐to‐moment timescale, providing evidence that patterns of these signals during sensitive windows of development influence neurocircuit formation across species and thus may be an evolutionarily conserved process that shapes the developing brain. Next, attention is drawn to emerging themes which provide a framework for future directions of research including the evaluation of functions, such as effortful control, that may be particularly vulnerable to unpredictability, sensitive periods, sex differences, cross‐cultural investigations, addressing causality, and unpredictability as a pathway by which other forms of ELA impact development. Finally, we provide suggestions for prevention and intervention, including the introduction of a screening instrument for the identification of children exposed to unpredictable experiences.

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Relationships between Depression and Executive Functioning in Adolescents: The Moderating Role of Unpredictable Home Environment

Cited by 13 publications

References 84 publications

Exposure to unpredictability and mental health: Validation of the brief version of the Questionnaire of Unpredictability in Childhood (QUIC-5) in English and Spanish

Exposure to unpredictability and mental health: Validation of the brief version of the Questionnaire of Unpredictability in Childhood (QUIC-5) in English and Spanish

Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome

Annual Research Review: The power of predictability – patterns of signals in early life shape neurodevelopment and mental health trajectories

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