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1.
Child Dev ; 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33423273

RESUMO

Studies of developmental trajectories of depression are important for understanding depression etiology. Existing studies have been limited by short time frames and no studies have explored a key factor: differential patterns of responding to life events. This article introduces a novel analytic technique, growth mixture modeling with structured residuals, to examine the course of youth depression in a large, prospective cohort (N = 11,641, ages 4-16.5, 96% White). Age-specific critical points were identified at ages 8 and 13 where depression symptoms spiked for a minority of children. Most depression risk was due to dynamic responses to environmental events, drawn not from a small pool of persistently depressed children, but a larger pool of children who varied across higher and lower symptom levels.

2.
Dev Psychopathol ; : 1-11, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33070801

RESUMO

Social cognitive deficits can have many negative consequences, spanning social withdrawal to psychopathology. Prior work has shown that child maltreatment may associate with poorer social cognitive skills in later life. However, no studies have examined this association from early childhood into adolescence. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 4,438), we examined the association between maltreatment (caregiver physical or emotional abuse; sexual or physical abuse), assessed repeatedly (every 1-3 years) from birth to age 9, and social cognitive skills at ages 7.5, 10.5, and 14 years. We evaluated the role of both the developmental timing (defined by age at exposure) and accumulation of maltreatment (defined as the number of occasions exposed) using a least angle regression variable selection procedure, followed by structural equation modeling. Among females, accumulation of maltreatment explained the most variation in social cognitive skills. For males, no significant associations were found. These findings underscore the importance of early intervention to minimize the accumulation of maltreatment and showcase the importance of prospective studies to understand the development of social cognition over time.

3.
Am J Epidemiol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33125040

RESUMO

The structured life course modeling approach (SLCMA) is a theory-driven analytic method that empirically compares multiple prespecified life course hypotheses characterizing time-dependent exposure-outcome relationships to determine which theory best fits the observed data. In this study, we performed simulations and empirical analyses to evaluate the performance of the SLCMA when applied to genome-wide DNA methylation (DNAm). Using simulations, we compared five statistical inference tests used with SLCMA (n=700), assessing the family-wise error rate, statistical power, and confidence interval coverage to determine whether inference based on these tests was valid in the presence of substantial multiple testing and small effects, two hallmark challenges of inference from omics data. In the empirical analyses, we evaluated the time-dependent relationship of childhood abuse with genome-wide DNAm (n=703). In simulations, selective inference and max-|t|-test performed best: both controlled family-wise error rate and yielded moderate statistical power. Empirical analyses using SLCMA revealed time-dependent effects of childhood abuse on DNAm. Our findings show that SLCMA, applied and interpreted appropriately, can be used in high-throughput settings to examine time-dependent effects underlying exposure-outcome relationships over the life course. We provide recommendations for applying the SLCMA in omics settings and encourage researchers to move beyond analyses of exposed versus unexposed.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33125721

RESUMO

BACKGROUND: Early-onset depression during childhood and adolescence is associated with a worse course of illness and outcome than adult onset. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over 13 years, we examined whether polygenic risk scores (PRS) that capture genetic risk for depression were associated with depressive symptom trajectories assessed from childhood to adolescence. METHODS: Data came from the Avon Longitudinal Study of Parents and Children, a prospective, longitudinal birth cohort (analytic sample = 7,308 youth). We analyzed the relationship between genetic susceptibility to depression and three time-dependent measures of depressive symptoms trajectories spanning 4-16.5 years of age (class, onset, and cumulative burden). Trajectories were constructed using a growth mixture model with structured residuals. PRS were generated from the summary statistics of a genome-wide association study of depression risk using data from the Psychiatric Genomics Consortium, UK Biobank, and 23andMe, Inc. We used MAGMA to identify gene-level associations with these measures. RESULTS: Youth were classified into six classes of depressive symptom trajectories: high/renitent (27.9% of youth), high/reversing (9.1%), childhood decrease (7.3%), late childhood peak (3.3%), adolescent spike (2.5%), and minimal symptoms (49.9%). PRS discriminated between youth in the late childhood peak, high/reversing, and high/renitent classes compared to the minimal symptoms and childhood decrease classes. No significant associations were detected at the gene level. CONCLUSIONS: This study highlights differences in polygenic loading for depressive symptoms across childhood and adolescence, particularly among youths with high symptoms in early adolescence, regardless of age-independent patterns.

6.
SSM Popul Health ; 12: 100661, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32964097

RESUMO

Recognizing that health outcomes are influenced by and occur within multiple social and physical contexts, researchers have used multilevel modeling techniques for decades to analyze hierarchical or nested data. Cross-Classified Multilevel Models (CCMM) are a statistical technique proposed in the 1990s that extend standard multilevel modeling and enable the simultaneous analysis of non-nested multilevel data. Though use of CCMM in empirical health studies has become increasingly popular, there has not yet been a review summarizing how CCMM are used in the health literature. To address this gap, we performed a scoping review of empirical health studies using CCMM to: (a) evaluate the extent to which this statistical approach has been adopted; (b) assess the rationale and procedures for using CCMM; and (c) provide concrete recommendations for the future use of CCMM. We identified 118 CCMM papers published in English-language literature between 1994 and 2018. Our results reveal a steady growth in empirical health studies using CCMM to address a wide variety of health outcomes in clustered non-hierarchical data. Health researchers use CCMM primarily for five reasons: (1) to statistically account for non-independence in clustered data structures; out of substantive interest in the variance explained by (2) concurrent contexts, (3) contexts over time, and (4) age-period-cohort effects; and (5) to apply CCMM alongside other techniques within a joint model. We conclude by proposing a set of recommendations for use of CCMM with the aim of improved clarity and standardization of reporting in future research using this statistical approach.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32910227

RESUMO

Pet ownership is common. Growing evidence suggests children form deep emotional attachments to their pets. Yet, little is known about children's emotional reactions to a pet's death. The goal of this study was to describe the relationship between experiences of pet death and risk of childhood psychopathology and determine if it was "better to have loved and lost than never to have loved at all". Data came from the Avon Longitudinal Study of Parents and Children, a UK-based prospective birth cohort (n = 6260). Children were characterized based on their exposure to pet ownership and pet death from birth to age 7 (never loved; loved without loss; loved with loss). Psychopathology symptoms at age 8 were compared across groups using multivariable linear regression. Psychopathology symptoms were higher among children who had loved with loss compared to those who had loved without loss (ß = 0.35, p = 0.013; 95% CI = 0.07, 0.63), even after adjustment for other adversities. This group effect was more pronounced in males than in females. There was no difference in psychopathology symptoms between children who had loved with loss and those who had never loved (ß = 0.20, p = 0.31, 95% CI = -0.18-0.58). The developmental timing, recency, or accumulation of pet death was unassociated with psychopathology symptoms. Pet death may be traumatic for children and associated with subsequent mental health difficulties. Where childhood pet ownership and pet bereavement is concerned, Tennyson's pronouncement may not apply to children's grief responses: it may not be "better to have loved and lost than never to have loved at all".

8.
Am J Psychiatry ; 177(10): 944-954, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32791893

RESUMO

OBJECTIVE: Efforts to prevent depression, the leading cause of disability worldwide, have focused on a limited number of candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank participants, the authors sought to systematically screen and validate a wide range of potential modifiable factors for depression. METHODS: Baseline data were extracted for 106 modifiable factors, including lifestyle (e.g., exercise, sleep, media, diet), social (e.g., support, engagement), and environmental (e.g., green space, pollution) variables. Incident depression was defined as minimal depressive symptoms at baseline and clinically significant depression at follow-up. At-risk individuals for incident depression were identified by polygenic risk scores or by reported traumatic life events. An exposure-wide association scan was conducted to identify factors associated with incident depression in the full sample and among at-risk individuals. Two-sample Mendelian randomization was then used to validate potentially causal relationships between identified factors and depression. RESULTS: Numerous factors across social, sleep, media, dietary, and exercise-related domains were prospectively associated with depression, even among at-risk individuals. However, only a subset of factors was supported by Mendelian randomization evidence, including confiding in others (odds ratio=0.76, 95% CI=0.67, 0.86), television watching time (odds ratio=1.09, 95% CI=1.05, 1.13), and daytime napping (odds ratio=1.34, 95% CI=1.17, 1.53). CONCLUSIONS: Using a two-stage approach, this study validates several actionable targets for preventing depression. It also demonstrates that not all factors associated with depression in observational research may translate into robust targets for prevention. A large-scale exposure-wide approach combined with genetically informed methods for causal inference may help prioritize strategies for multimodal prevention in psychiatry.


Assuntos
Depressão/prevenção & controle , Adulto , Bases de Dados como Assunto , Depressão/etiologia , Depressão/genética , Dieta , Exercício Físico/psicologia , Feminino , Humanos , Masculino , Análise da Randomização Mendeliana , Herança Multifatorial/genética , Fatores de Risco , Tempo de Tela , Higiene do Sono
10.
J Trauma Stress ; 33(5): 665-676, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32537815

RESUMO

Childhood maltreatment is consistently associated with poor outcomes. However, few epidemiological studies have examined the association between childhood maltreatment and adult resilience capacity, defined as one's perceived ability to cope successfully with challenges. This study aimed to determine associations between adult resilience capacity and specific types and features of childhood maltreatment. Participants were African American adults recruited from a public urban hospital in Atlanta, GA (N = 1,962) between 2005 and 2013. Childhood maltreatment, including witnessing domestic violence or physical, emotional, and sexual abuse, was assessed retrospectively using the Traumatic Events Inventory. Perceived resilience capacity was assessed using the Connor-Davidson Resilience Scale. Linear regressions were performed assessing the association between resilience capacity and childhood maltreatment exposure in general, as well as specific dimensions of exposure, including type, co-occurrence, and developmental timing, adjusting for covariates. Participants exposed to any maltreatment reported lower resilience capacity than unexposed peers, B = -0.38, SE = 0.04, p < .001. All maltreatment types were negatively associated with resilience capacity, even after adjusting for other lifetime trauma exposure. Only emotional abuse remained significantly associated with resilience capacity after accounting for current psychological distress, B = -0.11, SE = 0.05, p = .022. Maltreatment co-occurrence followed an inverse dose-response relationship with resilience capacity: For each additional maltreatment type, scores decreased by 0.18 units (SD = 0.02), p < .001. Finally, the developmental timing of maltreatment did not reveal any differential influences on resilience capacity. The results suggest that childhood emotional abuse and co-occurrence of maltreatment types may be particularly deleterious to adult resilience capacity.

12.
Psychol Med ; : 1-10, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32406816

RESUMO

BACKGROUND: Psychological resilience - positive psychological adaptation in the context of adversity - is defined and measured in multiple ways across disciplines. However, little is known about whether definitions capture the same underlying construct and/or share similar correlates. This study examined the congruence of different resilience measures and associations with sociodemographic factors and body mass index (BMI), a key health indicator. METHODS: In a cross-sectional sample of 1429 African American adults exposed to child maltreatment, we derived four resilience measures: a self-report scale assessing resiliency (perceived trait resilience); a binary variable defining resilience as low depression and posttraumatic stress (absence of distress); a binary variable defining resilience as low distress and high positive affect (absence of distress plus positive functioning); and a continuous variable reflecting individuals' deviation from distress levels predicted by maltreatment severity (relative resilience). Associations between resilience measures, sociodemographic factors, and BMI were assessed using correlations and regressions. RESULTS: Resilience measures were weakly-to-moderately correlated (0.27-0.69), though similarly patterned across sociodemographic factors. Women showed higher relative resilience, but lower perceived trait resilience than men. Only measures incorporating positive affect or resiliency perceptions were associated with BMI: individuals classified as resilient by absence of distress plus positive functioning had lower BMI than non-resilient (ß = -2.10, p = 0.026), as did those with higher perceived trait resilience (ß = -0.63, p = 0.046). CONCLUSION: Relatively low congruence between resilience measures suggests studies will yield divergent findings about predictors, prevalence, and consequences of resilience. Efforts to clearly define resilience are needed to better understand resilience and inform intervention and prevention efforts.

13.
Psychol Med ; : 1-8, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234096

RESUMO

BACKGROUND: There is a wealth of literature on the observed association between childhood trauma and psychotic illness. However, the relationship between childhood trauma and psychosis is complex and could be explained, in part, by gene-environment correlation. METHODS: The association between schizophrenia polygenic scores (PGS) and experiencing childhood trauma was investigated using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Norwegian Mother, Father and Child Cohort Study (MoBa). Schizophrenia PGS were derived in each cohort for children, mothers, and fathers where genetic data were available. Measures of trauma exposure were derived based on data collected throughout childhood and adolescence (0-17 years; ALSPAC) and at age 8 years (MoBa). RESULTS: Within ALSPAC, we found a positive association between schizophrenia PGS and exposure to trauma across childhood and adolescence; effect sizes were consistent for both child or maternal PGS. We found evidence of an association between the schizophrenia PGS and the majority of trauma subtypes investigated, with the exception of bullying. These results were comparable with those of MoBa. Within ALSPAC, genetic liability to a range of additional psychiatric traits was also associated with a greater trauma exposure. CONCLUSIONS: Results from two international birth cohorts indicate that genetic liability for a range of psychiatric traits is associated with experiencing childhood trauma. Genome-wide association study of psychiatric phenotypes may also reflect risk factors for these phenotypes. Our findings also suggest that youth at higher genetic risk might require greater resources/support to ensure they grow-up in a healthy environment.

15.
J Affect Disord ; 265: 255-262, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090749

RESUMO

BACKGROUND: Low maternal vitamin D levels [serum 25-hydroxyvitamin D (25(OH)D)] during pregnancy have been linked to offspring neuropsychiatric outcomes such as schizophrenia and autism, but studies on depression are lacking. We examined the association between maternal vitamin D status during pregnancy and offspring depression during childhood and adolescence and investigated whether any associations were modified by offspring genetic risk for depression. METHODS: Mother-singleton birth offspring pairs in the Avon Longitudinal Study of Parents and Children (ALSPAC) that had maternal 25(OH)D measurements, offspring genetic data, and offspring depression measures collected in childhood (mean age=10.6 years; n = 2938) and/or adolescence (mean age=13.8 years; n = 2485) were included in the analyses. Using multivariable logistic regression, we assessed associations between maternal vitamin D status and offspring polygenic risk score (PRS) for depression on childhood/adolescent depression risk. RESULTS: There was no evidence for an association between maternal vitamin D status during pregnancy and offspring depression in childhood (p = 0.72) or adolescence (p = 0.07). Offspring depression PRS were independently associated with childhood depression (p = 0.003), but did not interact with maternal vitamin D status. These results were robust to adjustments for potential confounders and different cut-offs for vitamin D insufficiency/deficiency. LIMITATIONS: 25(OH)D measurements were only available at a single time point during pregnancy. CONCLUSION: These findings suggest that maternal vitamin D status during pregnancy does not affect an offspring's risk for early life depression.

16.
Mol Psychiatry ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051548

RESUMO

Functional neurological (conversion) disorder (FND) is a neuropsychiatric condition whereby individuals present with sensorimotor symptoms incompatible with other neurological disorders. Early-life maltreatment (ELM) is a risk factor for developing FND, yet few studies have investigated brain network-trauma relationships in this population. In this neuroimaging-gene expression study, we used two graph theory approaches to elucidate ELM subtype effects on resting-state functional connectivity architecture in 30 patients with motor FND. Twenty-one individuals with comparable depression, anxiety, and ELM scores were used as psychiatric controls. Thereafter, we compared trauma endophenotypes in FND with regional differences in transcriptional gene expression as measured by the Allen Human Brain Atlas (AHBA). In FND patients only, we found that early-life physical abuse severity, and to a lesser extent physical neglect, correlated with corticolimbic weighted-degree functional connectivity. Connectivity profiles influenced by physical abuse occurred in limbic (amygdalar-hippocampal), paralimbic (cingulo-insular and ventromedial prefrontal), and cognitive control (ventrolateral prefrontal) areas, as well as in sensorimotor and visual cortices. These findings held adjusting for individual differences in depression/anxiety, PTSD, and motor phenotypes. In FND, physical abuse also correlated with amygdala and insula coupling to motor cortices. In exploratory analyses, physical abuse correlated connectivity maps overlapped with the AHBA spatial expression of three gene clusters: (i) neuronal morphogenesis and synaptic transmission genes in limbic/paralimbic areas; (ii) locomotory behavior and neuronal generation genes in left-lateralized structures; and (iii) nervous system development and cell motility genes in right-lateralized structures. These circuit-specific architectural profiles related to individual differences in childhood physical abuse burden advance our understanding of the pathophysiology of FND.

17.
Psychoneuroendocrinology ; 113: 104484, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918390

RESUMO

OBJECTIVES: Exposure to adversity has been linked to accelerated biological aging, which in turn has been shown to predict numerous physical and mental health problems. In recent years, measures of DNA methylation-based epigenetic age--known as "epigenetic clocks"--have been used to estimate accelerated epigenetic aging. Although a small number of studies have found an effect of adversity exposure on epigenetic age in children, none have investigated if there are "sensitive periods" when adversity is most impactful. METHODS: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC; n = 973), we tested the prospective association between repeated measures of childhood exposure to seven types of adversity on epigenetic age assessed at age 7.5 using the Horvath and Hannum epigenetic clocks. With a Least Angle Regression variable selection procedure, we evaluated potential sensitive period effects. RESULTS: We found that exposure to abuse, financial hardship, or neighborhood disadvantage during sensitive periods in early and middle childhood best explained variability in the deviation of Hannum-based epigenetic age from chronological age, even after considering the role of adversity accumulation and recency. Secondary sex-stratified analyses identified particularly strong sensitive period effects. These effects were undetected in analyses comparing children "exposed" versus "unexposed" to adversity. We did not identify any associations between adversity and epigenetic age using the Horvath epigenetic clock. CONCLUSIONS: Our results suggest that adversity may alter methylation processes in ways that either directly or indirectly perturb normal cellular aging and that these effects may be heightened during specific life stages.

18.
Mol Psychiatry ; 25(7): 1430-1446, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31969693

RESUMO

Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8 × 10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3 × 10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.

19.
Biol Psychiatry ; 87(5): 419-430, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570195

RESUMO

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

20.
J Am Acad Child Adolesc Psychiatry ; 59(2): 283-295.e4, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31078631

RESUMO

OBJECTIVE: Exposure to interpersonal violence is a known risk factor for psychopathology. However, it is unclear whether there are sensitive periods when exposure is most deleterious. We aimed to determine whether there were time periods when physical or sexual violence exposure was associated with greater child psychopathology. METHOD: This study (N = 4,580) was embedded in Generation R, a population-based prospective birth cohort. Timing of violence exposure, reported through maternal reports (child age, 10 years) was categorized by age at first exposure, defined as: very early (0-3 years), early (4-5 years), middle (6-7 years), and late (8+ years) childhood. Using Poisson regression, we assessed the association between timing of first exposure and levels of internalizing and externalizing symptoms, using the Child Behavior Checklist at age 10 years. RESULTS: Violence exposure at any age was associated with higher internalizing (physical violence: risk ratio [RR] = 1.46, p < 0.0001; sexual violence: RR = 1.30, p < .0001) and externalizing symptoms (physical violence: RR = 1.52, p < 0.0001; sexual violence: RR = 1.31, p = 0.0005). However, the effects of violence were time dependent: compared to children exposed at older ages, children first exposed during very early childhood had greater externalizing symptoms. Sensitivity analyses suggested that these time-based differences emerged slowly across ages 1.5, 3, 6, and 10 years, showing a latency between onset of violence exposure and emergence of symptoms, and were unlikely to be explained by co-occurring adversities. CONCLUSION: Interpersonal violence is harmful to childhood mental health regardless of when it occurs. However, very early childhood may be a particularly sensitive period when exposure results in worse psychopathology outcomes. Results should be replicated in fully prospective designs.

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