Genetic and Environmental Risk Factors Associated With Trajectories of Depression Symptoms From Adolescence to Young Adulthood

Kwong, Alex S. F.; López-López, José A; Hammerton, Gemma; Manley, David; Timpson, Nicholas J.; Leckie, George; Pearson, Rebecca

doi:10.1001/jamanetworkopen.2019.6587

Cited by 115 publications

(89 citation statements)

References 75 publications

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“…We included individuals into our analysis if they had at least one measurement of depression symptoms in order to maximise power (Lopéz-Lopez et al, In press). Previous research on these data has shown that trajectory shapes and characteristics do not vary when comparing individuals with at least one or at least 4 measurements of depressive symptoms (Kwong, Manley, et al, 2019).…”

Section: Missing Datamentioning

confidence: 88%

“…Individual level trajectories then vary around this population average (i.e., each person can have their own trajectory, with their own intercept and slope that deviates from the population average). Previous analysis of these data has shown that changes in depressive symptoms over time are non-linear (Edwards et al, 2014;Kwong, Manley, et al, 2019), with depressive symptoms rising until the age of about 18, then decreasing until around the age of 22, before rising again towards the age of 24see Table 1. To model these non-linear trajectories, a multilevel quartic growth-curve polynomial model was chosen.…”

Section: Discussionmentioning

confidence: 98%

“…Polygenic risk scores (PRS), which sum the number of "risk" variants that an individual possesses for a trait weighted by their effect size (Martin, Daly, Robinson, Hyman, & Neale, 2018), can be used as an indicator of an individual's genetic liability to depression. Several studies have used depression PRS taken from GWAS of major depressive disorder or depressive symptoms in adult populations to investigate how they influence depressive symptomatology over development in younger populations (Halldorsdottir et al, 2019;Kwong, López-López, et al, 2019;Rice et al, 2018;Riglin et al, 2018). One study found that the influence of an MDD PRS on emotional problems increased with age with weaker effects in childhood which developed in adulthood (Riglin et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…One study found that the influence of an MDD PRS on emotional problems increased with age with weaker effects in childhood which developed in adulthood (Riglin et al, 2018). Two other studies have since used a developmental trajectory approach to identify 'classes' of individuals whose depressive symptoms differ across adolescence (Kwong, López-López, et al, 2019;Rice et al, 2018). These studies found evidence of somewhat differing trajectory classes based on age of onset and persistence of symptoms over time that were associated with depression PRS.…”

Section: Introductionmentioning

confidence: 99%

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Polygenic Risk for Depression is Associated with the Severity and Rate of Change in Depressive Symptoms Across Adolescence

Kwong

Morris

Pearson

et al. 2020

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Adolescence marks a period where depression will commonly onset and previous research using twin studies has suggested that genetic influences play a role in how depression develops and changes across adolescence. Recent genome-wide association studies have also shown that common genetic variants − which can be combined into a polygenic risk score (PRS) − are also implicated in depression. However, the role of PRS in adolescent depression and changes in adolescent depression is not yet understood. We aimed to examine the association between a PRS for depressive symptoms and depressive symptoms across adolescence and young adulthood, and how polygenic risk is associated with changes in depressive symptoms using two methods: cross-sectional analysis and multilevel growth curve modelling to examine the rate of change over time. Using data from over 6000 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) we examined associations between genetic liability to depressive symptoms (PRS for depressive symptoms) and self-reported depressive symptoms (short mood and feelings questionnaire over 9 occasions from 10-24 years). We examined cross-sectional associations at each age and longitudinal trajectories of depressive symptoms in a repeated measures framework using growth curve analysis. The PRS was associated with depressive symptoms throughout adolescence and young adulthood in cross-sectional and growth curve analyses, though associations were stronger in the latter analyses. Growth curve analyses also provided additional insights, demonstrating that individuals with a higher PRS had steeper trajectories of depressive symptoms across adolescence with a greater increasing rate of change. These results show that common genetics variants as indexed by a PRS for depressive symptoms influence both the severity and rate of change in adolescent depressive symptoms. Longitudinal data that make use of repeated measures designs have the potential to provide greater insights into the factors that influence the onset and persistence of adolescent depression.

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Section: Missing Datamentioning

confidence: 88%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polygenic Risk for Depression is Associated with the Severity and Rate of Change in Depressive Symptoms Across Adolescence

Kwong

Morris

Pearson

et al. 2020

Preprint

Self Cite

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“…PRS from a recent GWAS meta-analysis of depression predicted early onset MDD is better than late-onset ( 5 ), and in hospital-treated cases the iPSYCH study, PRS from both bipolar disorder (BIP) and schizophrenia (SCZ) were associated with earlier MDD onset ( 28 , 29 ). Another longitudinal study found that PRS from SCZ and attention deficit hyperactive disorder (ADHD) were associated with early adolescent rather than later-adolescent onset trajectories, suggesting shared genetic contributions for early onset MDD and other psychiatric and neurodevelopmental conditions ( 30 , 31 ). Different heritabilities have also been found between depression occurring during the perinatal period (e.g.…”

Section: Using Manifestations To Understand Etiologymentioning

confidence: 99%

Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies

Cai

Choi

Fried

2020

Human Molecular Genetics

102

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With progress in genome-wide association studies of depression, from identifying zero hits in ~16 000 individuals in 2013 to 223 hits in more than a million individuals in 2020, understanding the genetic architecture of this debilitating condition no longer appears to be an impossible task. The pressing question now is whether recently discovered variants describe the etiology of a single disease entity. There are a myriad of ways to measure and operationalize depression severity, and major depressive disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders-5 can manifest in more than 10 000 ways based on symptom profiles alone. Variations in developmental timing, comorbidity and environmental contexts across individuals and samples further add to the heterogeneity. With big data increasingly enabling genomic discovery in psychiatry, it is more timely than ever to explicitly disentangle genetic contributions to what is likely ‘depressions’ rather than depression. Here, we introduce three sources of heterogeneity: operationalization, manifestation and etiology. We review recent efforts to identify depression subtypes using clinical and data-driven approaches, examine differences in genetic architecture of depression across contexts, and argue that heterogeneity in operationalizations of depression is likely a considerable source of inconsistency. Finally, we offer recommendations and considerations for the field going forward.

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Physical Activity Throughout Adolescence and Peak Hip Strength in Young Adults

et al. 2020

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IMPORTANCE Peak bone strength, which occurs in early adulthood, is an important marker of the future risk of osteoporosis. It is therefore important to identify modifiable early life factors that are associated with the attainment of peak hip strength. OBJECTIVE To investigate the association of time spent in moderate to vigorous-intensity and lightintensity physical activity throughout adolescence with peak hip strength in adulthood. DESIGN, SETTING, AND PARTICIPANTS The Avon Longitudinal Study of Parents and Children is a prospective birth cohort study that initially recruited all pregnant women residing within the catchment area of 3 health authorities in southwest England who had an expected delivery date between April 1, 1991, and December 31, 1992. In total, 15 454 eligible pregnant women were enrolled, and 15 589 infants were delivered. Of those, 14 901 infants were alive at age 1 year. The present analysis examined 2569 healthy offspring who had valid physical activity measurements obtained during a clinical assessment for at least 1 age (12, 14, 16, and/or 25 years), with up to 4 repeated accelerometer assessments performed (1 per age-associated clinical visit). Data were analyzed from June 2019 to June 2020. EXPOSURES Trajectories of accelerometer-assessed time spent in moderate to vigorous-intensity and light-intensity physical activity at ages 12, 14, 16, and 25 years (measured in minutes per day) were identified using latent trajectory modeling. Moderate to vigorous-intensity and light-intensity physical activity were determined using established thresholds of acceleration counts per minute. MAIN OUTCOMES AND MEASURES Femur neck bone mineral density (BMD; measured in g/cm 2) at age 25 years assessed by dual-energy radiography absorptiometry scans of the hip. RESULTS A total of 2569 participants (1588 female participants [62%]) were included in the analysis. Male participants spent more time in moderate to vigorous-intensity activity at each age and had greater adult femur neck BMD than female participants. For each sex, 3 moderate to vigorous-intensity trajectory subgroups and 3 light-intensity trajectory subgroups were identified. With regard to the moderate to vigorous-intensity trajectories, most male participants (85%) were in the low adolescent subgroup, with only 6% and 9% in the high early-adolescent and high mid-adolescent subgroups, respectively. Moderate to vigorous-intensity trajectories in female participants were divided into low adolescent-low adult (73%), low adolescent-high adult (8%), and high adolescent (19%) subgroups. Light-intensity physical activity trajectories were classified into low nonlinear, moderate decreasing, and high decreasing subgroups for both sexes. Femur neck BMD in male participants was greater in the high early-adolescent subgroup (0.38 g/cm 2 ; 95% CI, 0.11-0.66 g/cm 2) and the high mid-adolescent subgroup (0.33 g/cm 2 ; 95% CI, 0.07-0.60 g/cm 2) compared with the low adolescent (reference) subgroup. Femur neck BMD in female participants was greater in the high...

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Genetic and Environmental Risk Factors Associated With Trajectories of Depression Symptoms From Adolescence to Young Adulthood

Cited by 115 publications

References 75 publications

Polygenic Risk for Depression is Associated with the Severity and Rate of Change in Depressive Symptoms Across Adolescence

Polygenic Risk for Depression is Associated with the Severity and Rate of Change in Depressive Symptoms Across Adolescence

Reviewing the genetics of heterogeneity in depression: operationalizations, manifestations and etiologies

Physical Activity Throughout Adolescence and Peak Hip Strength in Young Adults

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