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

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          Key Points

          Question

          Are genetic and environmental risk factors associated with different trajectories of depression symptoms during adolescence and young adulthood?

          Findings

          In a cohort study of 3525 individuals observed from ages 10 to 24 years, both genetic and environmental risk factors were associated with childhood-persistent and early-adult–onset trajectories of depression symptoms, while adolescent-limited and childhood-limited trajectories were not associated with genetic risk factors.

          Meaning

          Differential patterns of timing and the nature of genetic and environmental risk factors were associated with different trajectory groups for depression symptoms, which could help to guide the timing and focus of prevention strategies.

          Abstract

          This cohort study examines the differential associations of genetic and environmental risk factors with trajectories of depression symptoms among individuals observed from ages 10 to 24 years in the Avon Longitudinal Study of Parents and Children (ALSPAC).

          Abstract

          Importance

          Less favorable trajectories of depressive mood from adolescence to early adulthood are associated with current and later psychopathology, impaired educational attainment, and social dysfunction, yet the genetic and environmental risk factors associated with these trajectories are not fully established. Examining what risk factors are associated with different trajectories of depressive mood could help identify the nature of depression symptoms and improve preventive interventions for those at most risk.

          Objective

          To examine the differential associations of genetic and environmental risk factors with trajectories of depression symptoms among individuals observed from ages 10 to 24 years.

          Design, Setting, and Participants

          In a longitudinal cohort study established in 1990 and currently ongoing (the Avon Longitudinal Study of Parents and Children [ALSPAC]), growth mixture modeling was used to identify trajectories of depression symptoms in 9394 individuals in the United Kingdom. Associations of different risk factors with these trajectories were then examined. Analysis was conducted between August 2018 and January 2019.

          Main Outcomes and Measures

          Trajectories were composed from depression symptoms measured using the Short Mood and Feelings Questionnaire at 9 occasions from ages 10 to 24 years. Risk factors included sex, a polygenic risk score taken from a recent genome-wide association study of depression symptoms, maternal postnatal depression, partner cruelty to the offspring’s mother when the child was aged 2 to 4 years, childhood anxiety at age 8 years, and being bullied at age 10 years.

          Results

          Data on all risk factors, confounders, and the outcome were available for 3525 individuals, including 1771 (50.2%) who were female. Trajectories were assessed between the mean (SD) age of 10.7 (0.3) years and mean (SD) age of 23.8 (0.5) years. Overall, 5 distinct trajectories of depression symptoms were identified: (1) stable low (2506 individuals [71.1%]), (2) adolescent limited (325 individuals [9.2%]), (3) childhood limited (203 individuals [5.8%]), (4) early-adult onset (393 individuals [11.1%]), and (5) childhood persistent (98 individuals [2.8%]). Of all the associations of risk factors with trajectories, sex (odds ratio [OR], 6.45; 95% CI, 2.89-14.38), the polygenic risk score for depression symptoms (OR, 1.47; 95% CI, 1.10-1.96), and childhood anxiety (OR, 1.30; 95% CI, 1.16-1.45) showed the strongest association with the childhood-persistent trajectory of depression symptoms compared with the stable-low trajectory. Maternal postnatal depression (OR, 2.39; 95% CI, 1.41-4.07) had the strongest association with the early-adult–onset trajectory, while partner cruelty to mother (OR, 2.30; 95% CI, 1.36-3.90) had the strongest association with the adolescent-limited trajectory. Bullying (OR, 8.08; 95% CI, 4.92-13.26) showed the strongest association with the childhood-limited trajectory.

          Conclusions and Relevance

          The least favorable trajectories of depression symptoms (childhood persistent and early-adult onset) were associated with both genetic and environmental risk factors, but the 2 trajectories of limited duration that had resolved by early adulthood (childhood limited and adolescent limited) were not associated with the polygenic risk score or maternal postnatal depression. Bullying was strongly associated with both the childhood-persistent and childhood-limited trajectories, suggesting that this risk factor may have a time-specific effect. These findings suggest that examining genetic and multiple time-specific environmental antecedents could help identify trajectories of varying onset and chronicity.

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          Most cited references41

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          Subthreshold depression in adolescence and mental health outcomes in adulthood.

          There is increasing interest in the extent to which individuals with subthreshold depression face increased risks of subsequent major depression and other disorders. To examine linkages between the extent of depressive symptoms (asymptomatic, subthreshold, major depression) at ages 17 to 18 years and mental health outcomes up to age 25 years in a New Zealand birth cohort. Data were gathered during the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of 1265 New Zealand children (635 males, 630 females). General community sample. The analysis was based on 1006 participants who represented 80% of the original cohort. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptom criteria for major depression and anxiety disorder, treatment-seeking, suicidal ideation, and suicide attempt. There were significant associations (P<.01) between the extent of depression at ages 17 to 18 years and rates of subsequent depressive symptoms, major depression, treatment for depression, anxiety disorder, treatment for anxiety disorder, suicidal ideation, and suicide attempts. After adjustment for covariate factors, the extent of depression at ages 17 to 18 years remained associated with later depression and suicidal tendencies. Planned comparisons showed that sample members with subthreshold depression had a similar prognosis to those meeting criteria for major depression. Findings suggest that sample members with subthreshold depression are a group with elevated risks of later depression and suicidal behaviors. Current diagnostic procedures, which classify people with subthreshold depression into complex discrete groups, might obscure the fact that depressive symptoms are dimensional and range from none to severe.
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            Maternal depression during pregnancy and the postnatal period: risks and possible mechanisms for offspring depression at age 18 years.

            Some small studies suggest that maternal postnatal depression is a risk factor for offspring adolescent depression. However, to our knowledge, no large cohort studies have addressed this issue. Furthermore, only 1 small study has examined the association between antenatal depression and later offspring depression. Understanding these associations is important to inform prevention. To investigate the hypothesis that there are independent associations between antenatal and postnatal depression with offspring depression and that the risk pathways are different, such that the risk is moderated by disadvantage (low maternal education) with postnatal depression but not with antenatal depression. Prospective investigation of associations between symptoms of antenatal and postnatal parental depression with offspring depression at age 18 years in a UK community-based birth cohort (Avon Longitudinal Study of Parents and Children) with data from more than 4500 parents and their adolescent offspring. Diagnosis of offspring aged 18 years with major depression using the International Classification of Diseases, 10th Revision. Antenatal depression was an independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003) more likely to have depression at age 18 years for each standard deviation increase in maternal depression score antenatally, independent of later maternal depression. Postnatal depression was also a risk factor for mothers with low education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to have depression for each standard deviation increase in postnatal depression score. However, for more educated mothers, there was little association (odds ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education moderated the effects of postnatal but not antenatal depression. Paternal depression antenatally was not associated with offspring depression, while postnatally, paternal depression showed a similar pattern to maternal depression. The findings suggest that treating maternal depression antenatally could prevent offspring depression during adulthood and that prioritizing less advantaged mothers postnatally may be most effective.
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              Adolescent subthreshold-depression and anxiety: psychopathology, functional impairment and increased suicide risk.

               Subthreshold-depression and anxiety have been associated with significant impairments in adults. This study investigates the characteristics of adolescent subthreshold-depression and anxiety with a focus on suicidality, using both categorical and dimensional diagnostic models.  Data were drawn from the Saving and Empowering Young Lives in Europe (SEYLE) study, comprising 12,395 adolescents from 11 countries. Based on self-report, including Beck Depression Inventory-II (BDI-II), Zung Self-Rating Anxiety Scale (SAS), Strengths and Difficulties Questionnaire (SDQ) and Paykel Suicide Scale (PSS) were administered to students. Based on BDI-II, adolescents were divided into three groups: nondepressed, subthreshold-depressed and depressed; based on the SAS, they were divided into nonanxiety, subthreshold-anxiety and anxiety groups. Analyses of Covariance were conducted on SDQ scores to explore psychopathology of the defined groups. Logistic regression analyses were conducted to explore the relationships between functional impairments, suicidality and subthreshold and full syndromes.  Thirty-two percent of the adolescents were subthreshold-anxious and 5.8% anxious, 29.2% subthreshold-depressed and 10.5% depressed, with high comorbidity. Mean scores of SDQ of subthreshold-depressed/anxious were significantly higher than the mean scores of the nondepressed/nonanxious groups and significantly lower than those of the depressed/anxious groups. Both subthreshold and threshold-anxiety and depression were related to functional impairment and suicidality. Subthreshold-depression and subthreshold-anxiety are associated with an increased burden of disease and suicide risk. These results highlight the importance of early identification of adolescent subthreshold-depression and anxiety to minimize suicide. Incorporating these subthreshold disorders into a diagnosis could provide a bridge between categorical and dimensional diagnostic models. © 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.
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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                28 June 2019
                June 2019
                28 June 2019
                : 2
                : 6
                : e196587
                Affiliations
                [1 ]Medical Research Center Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
                [2 ]School of Geographical Sciences, University of Bristol, Bristol, United Kingdom
                [3 ]Centre for Multilevel Modelling, University of Bristol, Bristol, United Kingdom
                [4 ]Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom
                [5 ]Centre for Academic Mental Health, University of Bristol, Bristol, United Kingdom
                [6 ]School of Education, University of Bristol, Bristol, United Kingdom
                Author notes
                Article Information
                Accepted for Publication: May 14, 2019.
                Published: June 28, 2019. doi:10.1001/jamanetworkopen.2019.6587
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2019 Kwong ASF et al. JAMA Network Open.
                Corresponding Author: Alex S. F. Kwong, MSc, School of Geographical Sciences, University of Bristol, University Road, Bristol BS8 1SS, United Kingdom ( alex.kwong@ 123456bristol.ac.uk ).
                Author Contributions: Mr Kwong had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Kwong, López-López, Manley, Timpson, Pearson.
                Acquisition, analysis, or interpretation of data: Kwong, López-López, Hammerton, Leckie.
                Drafting of the manuscript: Kwong, Manley, Timpson, Pearson.
                Critical revision of the manuscript for important intellectual content: Kwong, López-López, Hammerton, Timpson, Leckie, Pearson.
                Statistical analysis: Kwong, López-López, Hammerton, Leckie.
                Obtained funding: López-López.
                Administrative, technical, or material support: Kwong, López-López.
                Supervision: López-López, Manley, Timpson, Leckie, Pearson.
                Conflict of Interest Disclosures: None reported.
                Funding/Support: The Avon Longitudinal Study of Parents and Children (ALSPAC) receives its core support from the UK Medical Research Council (MRC), grant 102215/2/13/2 from the Wellcome Trust, and the University of Bristol. A comprehensive list of grant funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/). This research was specifically funded by grant 08426812/Z/07/Z from the Wellcome Trust, grants 076467/Z/05/Z and 092731 from the Wellcome Trust and the MRC, grant MR/M006727/1 from the MRC, grant PD301198-SC101645 from the National Institutes of Health, grant FP/2007-2013 from the European Research Council under the European Union’s Seventh Framework Programme, and grants 758813, MHINT and 669545, and DevelopObese from the European Research Council Grant Agreements. Mr Kwong is funded by an Economic and Social Research Council Advanced Quantitative Methods Studentship. Drs López-López and Pearson are supported by grant ES/P00881X/1 from the Economic and Social Research Council. Dr Hammerton is supported by a Sir Henry Wellcome Postdoctoral Fellowship (209138/Z/17/Z). Dr Timpson is a Wellcome Trust Investigator (grant 202802/Z/16/Z), is a program lead in the MRC Integrative Epidemiology Unit (project reference, MC_UU_12013/3), and works within the University of Bristol National Institute for Health Research Biomedical Research Centre and Cancer Research UK Integrative Cancer Epidemiology Programme (grant C18281/A19169).
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Additional Contributions: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses.
                Additional Information: The study website contains details of all the data that are available through a fully searchable data dictionary at http://www.bristol.ac.uk/alspac/researchers/access/. Permission to use the ALSPAC data is obtained through a proposal system managed by the ALSPAC executive. The code used for this analysis can be requested from the corresponding author. Part of this data was collected using REDCap ( https://projectredcap.org/resources/citations/).
                Article
                zoi190265
                10.1001/jamanetworkopen.2019.6587
                6604106
                31251383
                aa2ae05a-222c-4186-9cf8-5e5b39a54cd3
                Copyright 2019 Kwong ASF et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 12 March 2019
                : 14 May 2019
                Funding
                Funded by: UK Medical Research Council
                Funded by: Wellcome Trust
                Funded by: University of Bristol
                Funded by: Wellcome Trust
                Funded by: Wellcome Trust
                Funded by: MRC
                Funded by: MRC
                Funded by: National Institutes of Health
                Funded by: European Research Council
                Funded by: European Research Council
                Funded by: Economic and Social Research Council
                Funded by: Economic and Social Research Council
                Funded by: Sir Henry Wellcome Postdoctoral Fellowship
                Funded by: Wellcome Trust Investigator
                Funded by: National Institute for Health Research
                Categories
                Research
                Original Investigation
                Online Only
                Psychiatry

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