Gemma Hammerton

Antecedents of New-Onset Major Depressive Disorder in Children and Adolescents at High Familial Risk

Importance Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational outcomes. Objectives To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents. Design, Setting, and Participants This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean [SD] age of 12.4 [2.0] years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up. Main Outcomes and Measures The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score. Results On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (&bgr; = 0.12, P = .03) and fear and/or anxiety (&bgr; = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (&bgr; = −0.08, P = .14) and low mood (&bgr; = −0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents. Conclusions and Relevance There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity.

Association between Maternal Depression Symptoms across the First Eleven Years of Their Child’s Life and Subsequent Offspring Suicidal Ideation

Depression is common, especially in women of child-bearing age; prevalence estimates for this group range from 8% to 12%, and there is robust evidence that maternal depression is associated with mental health problems in offspring. Suicidal behaviour is a growing concern amongst young people and those exposed to maternal depression are likely to be especially at high risk. The aim of this study was to utilise a large, prospective population cohort to examine the relationship between depression symptom trajectories in mothers over the first eleven years of their child’s life and subsequent adolescent suicidal ideation. An additional aim was to test if associations were explained by maternal suicide attempt and offspring depressive disorder. Data were utilised from a population-based birth cohort: the Avon Longitudinal Study of Parents and Children. Maternal depression symptoms were assessed repeatedly from pregnancy to child age 11 years. Offspring suicidal ideation was assessed at age 16 years. Using multiple imputation, data for 10,559 families were analysed. Using latent class growth analysis, five distinct classes of maternal depression symptoms were identified (minimal, mild, increasing, sub-threshold, chronic-severe). The prevalence of past-year suicidal ideation at age 16 years was 15% (95% CI: 14-17%). Compared to offspring of mothers with minimal symptoms, the greatest risk of suicidal ideation was found for offspring of mothers with chronic-severe symptoms [OR 3.04 (95% CI 2.19, 4.21)], with evidence for smaller increases in risk of suicidal ideation in offspring of mothers with sub-threshold, increasing and mild symptoms. These associations were not fully accounted for by maternal suicide attempt or offspring depression diagnosis. Twenty-six percent of non-depressed offspring of mothers with chronic-severe depression symptoms reported suicidal ideation. Risk for suicidal ideation should be considered in young people whose mothers have a history of sustained high levels of depression symptoms, even when the offspring themselves do not have a depression diagnosis.

Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology

Objective Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior. Method Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms. Conclusion Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology.

Longitudinal symptom course in adults with recurrent depression: Impact on impairment and risk of psychopathology in offspring.

BACKGROUND Major depressive disorder (MDD) is common and is associated with an increased risk of psychopathology in offspring. However, depression shows considerable heterogeneity in its course over time. The aim of this study is to examine the relationship between parent depression symptom trajectories and (i) quality of life and social impairment and (ii) psychiatric disorder and depression symptoms in their offspring. METHOD Participants were from a longitudinal study of 337 parents with recurrent MDD and their adolescent offspring. Families were assessed on three occasions over four years. Parent depressive symptoms and current MDD diagnosis were assessed using the Schedules for Clinical Assessment in Neuropsychiatry. Adult quality of life and social impairment were derived from the EuroQol and current employment status. Psychiatric outcomes in offspring were assessed using the Child and Adolescent Psychiatric Assessment. RESULTS Using latent class growth analysis, three distinct classes of parental depression symptoms were identified (asymptomatic, mild, and chronic high). Parent depression classes were associated with their own quality of life and social impairment, and with psychiatric disorder and depression symptoms in their offspring. LIMITATIONS (i) We were unable to test associations with specific offspring disorders, (ii) we did not address the direction of effects underlying associations, and (iii) the sample consisted primarily of mothers and findings may not generalise to depressed fathers. CONCLUSION Longitudinal assessments of depressive symptoms in parents could help to identify families who are most in need of early intervention.

Association between obesity and depressive disorder in adolescents at high risk for depression

Objective:To examine the relationship between Body Mass Index (BMI) and depressive disorder in adolescents at high risk for depression.Design:Prospective longitudinal 3-wave study of offspring of parents with recurrent depression. Replication in population-based cohort study.Subjects:Three hundred and thirty-seven families where offspring were aged 9–17 years at baseline and 10–19 years at the final data point. Replication sample of adolescents from population-based cohort study aged 11–13 years at first assessment and 14–17 years at follow-up.Measurements:High risk sample used BMI, skin-fold thickness, Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)-defined major depressive disorder and depression symptoms using the Child and Adolescent Psychiatric Assessment (CAPA). Replication sample used BMI, DSM-IV depressive disorder and depression symptoms using the Development and Well-Being Assessment (DAWBA).Results:Two hundred and eighty-nine adolescents were included in the primary analyses. The mean BMI for each age group in this sample were significantly higher than population norms. There was no significant longitudinal association between categories of weight (or BMI) and new onset depressive disorder or depression symptoms. Similar results were found for skin-fold thickness. The association was also tested in a replication population-based sample and found to be non-significant in the subsample of offspring with mothers who had experienced recurrent depression in the past. BMI at age 12 years was, however, a significant predictor of depression symptoms but not of depressive disorder at age 15 years for the total unselected population.Conclusion:BMI does not significantly predict the development of depression in the offspring of parents with recurrent depression.

Examining whether offspring psychopathology influences illness course in mothers with recurrent depression using a high-risk longitudinal sample

Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = −.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls’ symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression.

Detecting recurrent major depressive disorder within primary care rapidly and reliably using short questionnaire measures

BACKGROUND Major depressive disorder (MDD) is often a chronic disorder with relapses usually detected and managed in primary care using a validated depression symptom questionnaire. However, for individuals with recurrent depression the choice of which questionnaire to use and whether a shorter measure could suffice is not established. AIM To compare the nine-item Patient Health Questionnaire (PHQ-9), the Beck Depression Inventory, and the Hospital Anxiety and Depression Scale against shorter PHQ-derived measures for detecting episodes of DSM-IV major depression in primary care patients with recurrent MDD. DESIGN AND SETTING Diagnostic accuracy study of adults with recurrent depression in primary care predominantly from Wales METHOD Scores on each of the depression questionnaire measures were compared with the results of a semi-structured clinical diagnostic interview using Receiver Operating Characteristic curve analysis for 337 adults with recurrent MDD. RESULTS Concurrent questionnaire and interview data were available for 272 participants. The one-month prevalence rate of depression was 22.2%. The area under the curve (AUC) and positive predictive value (PPV) at the derived optimal cut-off value for the three longer questionnaires were comparable (AUC = 0.86-0.90, PPV = 49.4-58.4%) but the AUC for the PHQ-9 was significantly greater than for the PHQ-2. However, by supplementing the PHQ-2 score with items on problems concentrating and feeling slowed down or restless, the AUC (0.91) and the PPV (55.3%) were comparable with those for the PHQ-9. CONCLUSION A novel four-item PHQ-based questionnaire measure of depression performs equivalently to three longer depression questionnaires in identifying depression relapse in patients with recurrent MDD.

Explaining risk for suicidal ideation in adolescent offspring of mothers with depression

Background It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent–child relationship. Method Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the childs life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. Results There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19–4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent–child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. Conclusions Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent–child relationship may also be beneficial.

Parental alcohol use and risk of behavioral and emotional problems in offspring

Objective The majority of studies that have examined parental alcohol use and offspring outcomes have either focused on exposure in the antenatal period or from clinical populations. This study sought to examine proximal and distal associations between parental alcohol use and offspring conduct problems and depressive symptoms in a population birth cohort. Methods We used prospective data from a large UK based population cohort (ALSPAC) to investigate the association between parental alcohol use, measured in units, (assessed at ages 4 and 12 years) with childhood conduct trajectories, (assessed on six occasions from 4 to 13.5 years, n = 6,927), and adolescent depressive symptoms (assessed on four occasions from ~13 to ~18 years, n = 5,539). Heavy drinking was defined as ≥21 units per week in mothers and partners who drank 4+ units daily. Results We found little evidence to support a dose response association between parental alcohol use and offspring outcomes. For example, we found insufficient evidence to support an association between maternal alcohol use at age 4 years and childhood conduct problems (childhood limited: OR = 1.00, 95% CI = .99, 1.01; adolescent onset: OR = 0.99, 95% CI = .98, 1.00; and early-onset persistent: OR = 0.99, 95% CI = .98, 1.00) per 1-unit change in maternal alcohol use compared to those with low levels of conduct problems. We also found insufficient evidence to support an association between maternal alcohol use at age 4 years and adolescent depressive symptoms (intercept: b = .001, 95% CI = -.01, .01, and slope: b = .003, 95% CI = -.03, .03) per 1-unit change in maternal alcohol use. Results remained consistent across amount of alcohol consumed (i.e., number of alcohol units or heavy alcohol use), parent (maternal self-reports or maternal reports of partner’s alcohol use), and timing of alcohol use (assessed at age 4 or age 12 years). Conclusions There is no support for an association between parental alcohol use during childhood and conduct and emotional problems during childhood or adolescence.

Depression and blood pressure in high-risk children and adolescents: an investigation using two longitudinal cohorts

Objective To examine the relationship between blood pressure and depressive disorder in children and adolescents at high risk for depression. Design Multisample longitudinal design including a prospective longitudinal three-wave high-risk study of offspring of parents with recurrent depression and an on-going birth cohort for replication. Setting Community-based studies. Participants High-risk sample includes 281 families where children were aged 9–17 years at baseline and 10–19 years at the final data point. Replication cohort includes 4830 families where children were aged 11–14 years at baseline and 14–17 years at follow-up and a high-risk subsample of 612 offspring with mothers that had reported recurrent depression. Main outcome measures The new-onset of Diagnostic and Statistical Manual of Mental Disorder, fourth edition defined depressive disorder in the offspring using established research diagnostic assessments—the Child and Adolescent Psychiatric Assessment in the high-risk sample and the Development and Wellbeing Assessment in the replication sample. Results Blood pressure was standardised for age and gender to create SD scores and childs weight was statistically controlled in all analyses. In the high-risk sample, lower systolic blood pressure at wave 1 significantly predicted new-onset depressive disorder in children (OR=0.65, 95% CI 0.44 to 0.96; p=0.029) but diastolic blood pressure did not. Depressive disorder at wave 1 did not predict systolic blood pressure at wave 3. A significant association between lower systolic blood pressure and future depression was also found in the replication cohort in the second subset of high-risk children whose mothers had experienced recurrent depression in the past. Conclusions Lower systolic blood pressure predicts new-onset depressive disorder in the offspring of parents with depression. Further studies are needed to investigate how this association arises.