Risk Of Psychopathology In Offspring Research Articles

Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2Years of Age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2years of age, or if associations were due to confounding variables. Methods Data from 815 mother-child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = - 0.20, p < 0.001) and internalizing (semi-partial rdiet = - 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = - 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = - 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment.

The role of glucocorticoid, interleukin-1\u03b2, and antioxidants in prenatal stress effects on embryonic microglia

Maternal stress during pregnancy is associated with an increased risk of psychopathology in offspring. Resident immune cells of the brain, microglia, may be mediators of prenatal stress and altered neurodevelopment. Here, we demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin-1β (IL-1β), nor the glucocorticoid hormone, corticosterone, recapitulated the full effects of prenatal stress on the morphology of microglial cells in the cortical plate of embryonic mice; IL-1β effects showed greater similarity to prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has antioxidant properties, moderated the effects of prenatal stress on microglia. Microglia changes with prenatal stress were also sensitive to the antioxidant, N-acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.

The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders

BackgroundTwo major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. MethodsClinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6–17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. ResultsOffspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8–34.6) and substance use disorders HR=5.0(1.1–21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LimitationsLimited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. ConclusionsOur results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD.

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

BackgroundMajor 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. MethodParticipants 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. ResultsUsing 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. ConclusionLongitudinal assessments of depressive symptoms in parents could help to identify families who are most in need of early intervention.

Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors

Intergenerational effects of trauma have been observed clinically in a wide range of populations, and parental PTSD has been associated with an increased risk for psychopathology in offspring. In studies of Holocaust survivor offspring, parental PTSD, and particularly maternal PTSD, has been associated with increased risk for PTSD, low basal urinary cortisol excretion and enhanced cortisol suppression in response to dexamethasone. Such findings implicate maternally derived glucocorticoid programming in the intergenerational transmission of trauma-related consequences, potentially resulting from in utero influences or early life experiences. This study investigated the relative influence of Holocaust exposure and PTSD in mothers and fathers on glucocorticoid sensitivity in offspring. Eighty Holocaust offspring and 15 offspring of non-exposed Jewish parents completed evaluations and provided blood and urine samples. Glucocorticoid sensitivity was evaluated using the lysozyme suppression test (LST), an in vitro measure of glucocorticoid receptor sensitivity in a peripheral tissue, the dexamethasone suppression test (DST), and 24-h urinary cortisol excretion. Maternal PTSD was associated with greater glucocorticoid sensitivity in offspring across all three measures of glucocorticoid function. An interaction of maternal and paternal PTSD on the DST and 24-h urinary cortisol showed an effect of decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. Although indirect, these findings are consistent with the hypothesis that epigenetic programming may be involved in the intergenerational transmission of trauma-related effects on glucocorticoid regulation.

740 – All about ‘u’: associations between prenatal depression, and foetal and infant stress responses in the developing world

Introduction Prenatal maternal depression predicts disturbances in stress responses and an increased risk of psychopathology in offspring. However the foetal origins of these programming influences on the offspring's stress response mechanism are unclear. Furthermore, there are no inquiries into this issue from the developing world, where high rates of prenatal depression (25-45%) are reported. Aim To explore associations between prenatal depression and, foetal and infant responsivity, in a sample from rural South India. Methods 67 pregnant women in their third trimester with high prenatal depression scores and 66 controls were assessed for their foetus’ responsivity to repeated vibroacoustic stimulation by measuring foetal heart rate responses. At 1.5-3 months postbirth, infant cortisol responses to immunisation and infant temperament were measured. Results A curvilinear relationship existed between prenatal depression and foetal responsivity to a potential stressor (R2=0.98, p=0.02). Foetuses of mothers with both very high and very low levels of depression showed elevated responses compared to the foetuses of mothers with moderate levels of depression. Prenatal depression predicted elevated infant cortisol responsivity independent of postnatal depression and other confounders (B=13.08, p=0.02). Quintile analysis revealed this relationship to be U shaped (R2=0.20, p=0.02), similar to the relationship between prenatal depression and foetal responsivity. There were no associations between prenatal depression and difficult infant temperament. Conclusions The findings provide the first evidence of a curvilinear relationship between prenatal depression and offspring stress responsivity from the developing world suggesting that intra-uterine exposure to moderate stress levels may be beneficial in the context of socio-economic disadvantage.

Mental disorders in offspring of parents with bipolar and major depressive disorders

There is limited information on the specificity of associations between parental bipolar disorder (BPD) and major depressive disorder (MDD) and the risk of psychopathology in offspring. The chief aim of the present study was to investigate the association between mood disorder subtypes in the two parents and mental disorders in the offspring. A total of 376 offspring (aged 6.0-17.9 years; mean=11.5years) of 72 patients with BPD (139 offspring), 56 patients with MDD (110 offspring), and 66 controls (127 offspring) participated in a family study conducted in two university hospital centers in Switzerland. Probands, offspring, and biological co-parents were interviewed by psychologists blind to proband diagnoses, using a semi-structured diagnostic interview. Rates of mood and anxiety disorders were elevated among offspring of BPD probands (34.5% any mood; 42.5% any anxiety) and MDD probands (25.5% any mood; 44.6% any anxiety) as compared to those of controls (12.6% any mood; 22.8% any anxiety). Moreover, recurrent MDD was more frequent among offspring of BPD probands (7.9%) than those of controls (1.6%). Parental concordance for bipolar spectrum disorders was associated with a further elevation in the rates of mood disorders in offspring (64.3% both parents versus 27.2% one parent). These findings provide unique information on the broad manifestations of parental mood disorders in their offspring. The earlier onset and increased risk of recurrent MDD in the offspring of parents with BPD compared to those of controls suggests that the episodicity characterizing BPD may emerge in childhood and adolescence.

P-106 - Risk of mental disorders in children of parents with alcohol or heroin dependence: a controlled high risk study

Children of patients with substance use disorders (SUD) are at high risk for mental disorders. The effects of specific SUD in both parents on the risk of psychopathology in offspring have hardly been studied. To gain a better understanding of the morbid risk of these children. To assess, 1) the associations between alcohol dependence (AD) or heroin dependence (HD) in patients and psychopathology in their children; 2) the morbid risk conferred by having a second parent with SUD. The sample included 276 children aged from 6 to 17.9 years (mean age = 11.5): 23 children of 15 patients with HD, 101 offspring of 50 patients with AD, 152 children of 81 orthopedic patients (controls) and 158 biological co-parents of the children. Subjects were interviewed by psychologists blind to patient diagnoses, using a semi-structured diagnostic interview. 1) Children of HD or AD patients had largely elevated rates of recurrent major depressive disorder and children of HD patients were also at an increased risk for ADHD and SUD; 2) There were interactions between drug disorders and alcohol disorders in both parents to increase the risk of early SUD in offspring. The early manifestations of mental disorders in children of SUD patients emphasize the need for prompt identification and treatment of these disorders. The involvement of co-parental disorders in the development of offspring psychopathology highlights the need to pay clinical attention not only to the patient, but also to the co-parent in order to optimize prevention in offspring.

Maternal smoking cessation and reduced academic and behavioral problems in offspring

BackgroundThere is some debate whether smoking during pregnancy causes or is only a risk factor for negative academic outcomes and increased risk of psychopathology in offspring. This study evaluated whether maternal smoking cessation would reduce the risk of adverse outcomes in school-aged children. MethodsWomen completed an online survey that included items about child scholastic performance and the Child Behavior Checklist (CBCL). Mothers were divided based on pre-pregnancy and pregnancy smoking status into: (1) Nonsmokers (N=320); (2) Women that smoked in the 3 months preceding and throughout pregnancy (Smokers, N=83); and (3) Smoking before, but not during pregnancy (Quitters, N=72). ResultsThe Smokers and Quitters groups each had lower education and incomes compared to Nonsmokers but were indistinguishable from each other on these measures. The offspring of Smokers were more likely (p<.05) to be behind their peers on standardized tests in math (27.8%) relative to both Nonsmokers (17.4%) and Quitters (13.0%) with similar findings for reading. Smokers reported more behavioral problems by their children in several areas including Hyperactivity and Impulsivity, Social problems, and Externalizing problems including Aggression and Rule-Breaking. Further, the children of Quitters had significantly fewer Attention and Externalizing problems than Smokers. These outcomes were observed even after accounting for the variance attributable to maternal education and several other potential confounds. ConclusionsTogether, these findings indicate that smoking cessation is associated with reduced risk of having children with academic and neuropsychological difficulties. These outcomes are discussed within the framework that nicotine may be a neurobehavioral teratogen.

Parental disorders, childhood abuse, and binge eating in a large community sample

Genetic and nonshared environmental factors are implicated in the etiology of binge eating behaviors (BEB), with genetic risk expressed as parental psychopathology. Traumatic experiences including child abuse predict onset of BEB. It is not clear if each separately contribute to BEB, or whether parental pathology leads to abuse which in turn influences BEB. Data were obtained from the National Comorbidity Survey-Replication (N = 2960). Through structural equation modeling, we estimated unique and combined effects of mother's and father's internalizing (INT) and externalizing (EXT) disorders, and child abuse on BEB. Parental INT and EXT psychopathology contributed to child abuse and BEB. Abuse predicted BEB and partially mediated associations between parental psychopathology and BEB. Results emphasize the value of models that incorporate nature and nurture to understand risk for psychopathology in offspring, with childhood abuse being one mediator of how parental psychopathology may reflect genetic risk and influence environmental risk.

Psychopathology in the Offspring of Parents with Bipolar Disorder: A Controlled Study

To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psychiatric disorders in these youth. Using structured diagnostic interviews (Structured Clinical Interview for DSM-IV [SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. Compared with offspring of parents without mood disorders, high-risk youth had elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also had significantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk for subsequent bipolar disorder in high-risk samples.

Prenatal and perinatal influences on risk for psychopathology in childhood and adolescence.

The relationship between a range of prenatal and perinatal events and risk for psychopathology in offspring was examined. Prenatal and perinatal events investigated included maternal experiences, health, and substance use during pregnancy, obstetric complications, feeding practices, and infant health during the first year of life. Offspring diagnosis was based on structured interviews conducted with 579 adolescents on two occasions. Risk for later psychopathology was associated with a number of prenatal and perinatal factors. Major depression was associated with not being breast fed and maternal emotional problems during the pregnancy. Anxiety was chiefly associated with fever and illness during the first year of life and maternal history of miscarriage and stillbirth. Disruptive behavior disorder was associated with poor maternal emotional health during the pregnancy and birth complications. Risk for substance use disorder was associated with maternal use of substances during the pregnancy. Mediating effects of maternal depression, maternal-child conflict, and physical symptoms in the child, and moderating effects of gender of child and parental education were also evaluated. The limitations of this study are discussed and future research directions are suggested.