The Developmental Brain Age Is Associated With Adversity, Depression, and Functional Outcomes Among Adolescents

Drobinin, Vladislav; Gestel, Holly Van; Helmick, Carl; Schmidt, Matthias; Bowen, Chris V.; Uher, Rudolf

doi:10.1016/j.bpsc.2021.09.004

Cited by 23 publications

(30 citation statements)

References 52 publications

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“…In children and adolescents, brain age has been interpreted as an indicator of overall level of brain maturation (Franke et al, 2012; Brown et al, 2012). Longitudinal assessments in adolescence have shown brain age to be heritable, higher in females than males (Brouwer et al, 2021), and linked to psychopathology and psychosocial functioning (Drobinin et al, 2021; Cropley et al, 2021). However, the clinical and functional correlates of brain age in adolescence have not been fully established.…”

Section: Introductionmentioning

confidence: 99%

Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort

Holm

Leonardsen

Beck

et al. 2022

Preprint

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The temporal characteristics of brain maturation could potentially represent a mediating effect between pubertal development and life outcomes. Using a large longitudinal dataset of children aged 9-12 from the Adolescent Brain Cognitive Development (ABCD) study we tested the associations between pubertal status and brain maturation. Brain maturation was assessed using brain age prediction with a deep learning approach based on convolutional neural networks and minimally processed T1-weighted structural MRI data. Brain age prediction provided highly accurate and reliable estimates of individual age, with an overall mean absolute error of 0.7 and 1.4 years at the two timepoints respectively, and an intraclass correlation of 0.65. Linear mixed effects (LME) models accounting for age and sex showed that on average, advancing pubertal development by one pubertal stage was associated with a 2.4 months higher brain age across time points (β= 0.10, p<.001). Further, significant interactions with time demonstrated that higher rates of pubertal development were associated with larger positive changes in brain age over time (p<.001). These results demonstrate a link between sexual development and brain maturation in early adolescence, and provides a basis for further investigations of the complex sociobiological impacts of puberty on the adolescent brain and mind.

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Section: Introductionmentioning

confidence: 99%

Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort

Holm

Leonardsen

Beck

et al. 2022

Preprint

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“…To date, findings on the directionality of risk-associated-aging in youth are equivocal. In one study, an association between an environmental risk composite score and accelerated brain aging was detected, but was not driven meaningfully by parental education and income (Drobinin et al, 2021). Another study found that neighborhood disadvantage was associated with accelerated aging in early adolescence and delayed aging in later adolescence (Rakesh, Cropley, et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…We parse SES into specific components including income-to-needs ratio (INR), parent education, parent occupation, and public assistance utilization in the same model to account for shared variance. We hypothesized that these specific components of SES would be distinctly associated with brain aging; the expected direction of this effect remains unclear due to equivocal findings in the literature (Drobinin et al, 2021; Keding et al, 2021; Rakesh, Cropley, et al, 2021). Second, we explore links between brain age and concurrent parent-related problem behaviors to ground our findings in the literature linking brain age to mental health outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Less is known, however, about factors that contribute to the brain age gap. Although household SES has not been specifically examined in relation to brain age, accelerated brain aging has been shown to associate with greater childhood physical neglect (Keding et al, 2021), emotional/sexual abuse and exposure to violence (Drobinin et al, 2021), as well as neighborhood disadvantage in early adolescence with inverse findings in late adolescence (Rakesh, Cropley, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Relative Brain Age Is Associated with Socioeconomic Status and Anxiety/Depression Problems in Youth

Cohen

Ramphal

DeSerisy

et al. 2022

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Socioeconomic status (SES) has been linked to differences in brain structure and psychiatric risk across the lifespan. Despite many neuropsychiatric disorders emerging in childhood, few studies have examined the influence of SES on brain aging and psychopathology in youth. We re-analyzed relative brain age (RBA) data from the Healthy Brain Network to examine the influence of SES components (parent education, occupation, household income-to-needs ratio (INR), public assistance enrollment) on RBA. RBA was previously determined using covariation patterns for cortical morphology, white, and subcortical gray matter volumes without SES in predictive models. We also examined associations between RBA and psychiatric symptoms (child behavior checklist). Full case analysis included 470 youth (5-17 years; 61.3% male), self-identifying as White (55%), African American (15%), Hispanic (9%), or multiracial (17.2%). Mean household income was 3.95+/-2.33 (Mean+/-SD) times the federal poverty threshold. Multiple linear regression examined if 1) SES components associated with RBA, and 2) RBA associated with psychiatric symptoms. Models covaried for sex, scan location, and parent psychiatric diagnoses. RBA associated with public assistance (p = 0.03), parent occupation (p = 0.01), and parent psychiatric diagnosis (p = 0.01), but not with INR and parent education. Parent occupation (p = 0.02) and RBA (p = 0.04) associated with CBCL anxiety/depression scores. Components of SES associated with brain aging, underscoring the risk of omitting these factors in developmental brain research. Further, delayed brain aging was associated with low parental occupational prestige and child anxiety/depression scores, suggesting a possible biological pathway from SES to mental health risk.

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“…Recent research set out to explore the relationship between accelerated brain aging and major depressive disorder (MDD), a widespread, debilitating, and disabling psychiatric disorder [20] associated with cellular senescence [21,22] and cognitive decline [23]. Despite the positive association reported [11,[24][25][26][27][28], current studies still present several limitations.…”

Section: Introductionmentioning

confidence: 99%

Accelerated functional brain aging in major depressive disorder: evidence from a large scale fMRI analysis of Chinese participants

Luo,

Chen,

Qiu

et al. 2022

Preprint

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Major depressive disorder (MDD) is one of the most common mental health conditions that has been intensively investigated for its association with brain atrophy and mortality. Recent studies reveal that the deviation between the predicted and the chronological age can be a marker of accelerated brain aging to characterize MDD. However, current conclusions are usually drawn based on structural MRI information collected from Caucasian participants. The universality of this biomarker needs to be further validated by subjects with different ethnic/racial backgrounds and by different types of data. Here we make use of the REST-meta-MDD, a large scale resting-state fMRI dataset collected from multiple cohort participants in China. We develop a stacking machine learning model based on 1101 healthy controls, which estimates a subject's chronological age from fMRI with promising accuracy. The trained model is then applied to 1276 MDD patients from 24 sites. We observe that MDD patients exhibit a +4.43 years (p < 0.0001, Cohen's d = 0.35, 95% CI :1.86 − 3.91) higher brain-predicted age difference (brain-PAD) compared to controls. In the MDD subgroup, we observe a statistically significant +2.09 years (p < 0.05, Cohen's d = 0.134483) brain-PAD in antidepressant users compared to medication-free patients. The statistical relationship observed is further checked by three different machine learning algorithms. The positive brain-PAD observed in participants in China confirms the presence of accelerated brain aging in MDD patients. The utilization of functional brain connectivity for age estimation verifies existing findings from a new dimension.

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The Developmental Brain Age Is Associated With Adversity, Depression, and Functional Outcomes Among Adolescents

Cited by 23 publications

References 52 publications

Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort

Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort

Relative Brain Age Is Associated with Socioeconomic Status and Anxiety/Depression Problems in Youth

Accelerated functional brain aging in major depressive disorder: evidence from a large scale fMRI analysis of Chinese participants

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