Mood Disorders In Offspring Research Articles

Risk factors for mood disorders among offspring of parents with bipolar disorder: Findings from a discordant-sibling study

The purpose of this naturalistic, prospective study was to identify risk factors for mood disorders in offspring of parents with bipolar disorder (BPD) using the discordant-sibling design by comparing premorbid psychopathology or symptoms, temperament, personality traits and coping style as well as the perception of family-related characteristics among affected and unaffected siblings within the same family. This approach controls for confounding by unmeasured genetic and environmental factors shared within families. Our sample comprised 24 families of a parent with BPD with at least one child that developed BPD or major depressive disorder (n=31), and at least one child who did not. Offspring were followed for a mean duration of 16.2 (s.d: 4.6) years. Information was collected from the offspring themselves. Generalized linear mixed models only revealed differences in three dimensions of the Dimension of Temperament Survey-Revised (DOTS-R) version: Offspring with mood disorders scored higher on "Approach-withdrawal", "Rhythmicity for daily habits", and "Task orientation" than their unaffected siblings. The higher scores, and not lower scores as expected, on these temperament dimensions observed in offspring that subsequently developed mood disorders may reflect increased vulnerability, but they could also mirror premorbid mood swings or strategies to cope with them.

Gestational environmental enrichment prevents chronic social stress induced anxiety- and ethanol-related behaviors in offspring

Epidemiological surveys have shown a strong relationship between maternal stress and offspring's mood disorders. Growing evidence suggested that environmental enrichment (EE) improves cognitive function in models of psychiatric and neurological disorders. However, the potential protective effects of gestational EE on social stress-elicited mood disorders in offspring have not been studied. Knowing that the undeveloped brain is more sensitive to gestational environmental stimuli, we hypothesized that initiating cognitive stimulation, during gestation, would protect against social stress-induced behavioral alterations in adulthood. Therefore, the present study aimed to investigate the effects of gestational EE on social stress-elicited anxiety- and ethanol-related behaviors in adult offspring. EE consisted of free access, of dams, to tubular devices of different shapes, colors, and sizes that were changed regularly. After birth and weaning, young adult offspring were exposed to 19 days of social stress and anxiety-like behavior was evaluated by elevated plus maze, open field, and marbles burying tests. The two-bottle choice (TBC) drinking paradigm was used to assess stress-induced ethanol intake. Results showed that gestational EE prevented social stress-elicited anxiogenic-like effects with no differences in spontaneous locomotor activity. Moreover, in the TBC paradigm, mice pre-exposed to EE consistently showed a significantly decreased consumption and preference for ethanol with no effects on tastants' intakes. Interestingly, gestational EE increased serum BDNF levels, which showed a correlation with measures of anxiety- and ethanol-related behaviors. These findings indicate that some neurodevelopmental changes associated with prenatal EE may counteract adult social stress-induced behavioral alterations through a BDNF mechanism. Therefore, we propose that gestational EE has significant protective and beneficial effects on social stress-induced cognitive impairment. It can also alleviate anxiety-like behavior and subsequent excessive alcohol consumption.

Predicting the risk and timing of major mood disorder in offspring of bipolar parents: exploring the utility of a neural network approach

BackgroundBipolar disorder onset peaks over early adulthood and confirmed family history is a robust risk factor. However, penetrance within families varies and most children of bipolar parents will not develop the illness. Individualized risk prediction would be helpful for identifying those young people most at risk and to inform targeted intervention. Using prospectively collected data from the Canadian Flourish High-risk Offspring cohort study available in routine practice, we explored the use of a neural network, known as the Partial Logistic Artificial Neural Network (PLANN) to predict the time to diagnosis of major mood disorders in 1, 3 and 5-year intervals.ResultsOverall, for predictive performance, PLANN outperformed the more traditional discrete survival model for 3-year and 5-year predictions. PLANN was better able to discriminate or rank individuals based on their risk of developing a major mood disorder, better able to predict the probability of developing a major mood disorder and better able to identify individuals who would be diagnosed in future time intervals. The average AUC achieved by PLANN for 5-year prediction was 0.74, which indicates good discrimination.ConclusionsThis evaluation of PLANN is a useful step in the investigation of using neural networks as tools in the prediction of mood disorders in at-risk individuals and the potential that neural networks have in this field. Future research is needed to replicate these findings in a separate high-risk offspring sample.

Sirt7-p21 Signaling Pathway Mediates Glucocorticoid-Induced Inhibition of Mouse Neural Stem Cell Proliferation.

Prenatal glucocorticoid (GC) overexposure impacts fetal hippocampal neural stem cells (NSCs) and increases the risk for relative cognitive and mood disorders in offspring. However, the precise underlying mechanisms remain elusive. Here, we treated mouse hippocampal NSCs with dexamethasone (DEX) in vitro and found that DEX inhibited cell proliferation and Sirt7 expression. In addition, prenatal mouse overexposure to DEX induced the suppression of Sirt7 in the hippocampus of offspring. Sirt7 knockdown significantly decreased the percentage of proliferating cells but did not further reduce the NSC proliferation rate in the presence of DEX, whereas Sirt7 overexpression rescued DEX-induced inhibition of hippocampal NSC proliferation. Moreover, DEX inhibited Sirt7 expression through the glucocorticoid receptor (GR), and p21 was found to mediate the functional effect of DEX-induced Sirt7 suppression. In conclusion, our data demonstrate for the first time the effect of DEX on the Sirt7-p21 pathway in hippocampal NSCs, identifying a new potential therapeutic target for prenatal GC overexposure-related neurodevelopmental disorders in offspring.

Prenatal tobacco use and the risk of mood disorders in offspring: a systematic review and meta-analysis.

It is plausible that offspring born to mothers using tobacco during pregnancy may have increased risk of mood disorders (depression and bipolar disorders); however, mixed results have been reported. We conducted a systematic review and meta-analysis to investigate the magnitude and consistency of associations reported between prenatal tobacco use and mood disorders in offspring. We systematically searched EMBASE, SCOPUS, PubMed and Psych-INFO for studies on mood disorders and prenatal tobacco use. Methodological quality of studies was assessed with the revised Newcastle-Ottawa Scale. We estimated pooled relative risk (RR) with inverse variance weighted random-effects meta-analysis. We performed leave-one-out analyses, and stratified analyses by a subgroup (depression and bipolar disorder). Potential publication bias was assessed by inspection of the funnel plot and Egger's test for regression asymmetry. This study protocol was prospectively registered in PROSPERO (CRD42017060037). Eight cohort and two case-control studies were included in the final meta-analysis. We found an increased pooled relative risk of mood disorders in offspring exposed to maternal prenatal tobacco use RRs 1.43 (95% CI 1.27-1.60) compared to no prenatal tobacco use. Similarly, the pooled relative risks of bipolar and depressive disorders in offspring were 1.44, (95% CI 1.15-1.80) and 1.44, (95% CI 1.21-1.71), respectively. Moreover, the pooled estimated risk of mood disorders was not significantly attenuated in the studies that reported sibling comparison results [RR = 1.21 (95% CI 1.04-1.41)]. Taken together, there was strong evidence for a small (RR < 2) association between prenatal tobacco use and mood disorders in offspring.

Psychopathological precursors of the onset of mood disorders in offspring of parents with and without mood disorders: results of a 13-year prospective cohort high-risk study.

There is still limited evidence from prospective high-risk research on the evolution of specific disorders that may emerge early in the development of mood disorders. Moreover, few studies have examined the specificity of mood disorder subtypes among offspring of parents with both major subtypes of mood disorders and controls based on prospective tracking across the transition from childhood to adulthood. Our specific objectives were to (a) identify differences in patterns of psychopathological precursors among youth with (hypo)mania compared to MDD and (b) examine whether these patterns differ by subtypes of parental mood disorders. Our data stem from a prospective cohort study of 449 directly interviewed offspring (51% female, mean age 10.1years at study intake) of 88 patients with BPD, 71 with MDD, 30 with substance use disorders and 60 medical controls. The mean duration of follow-up was 13.2years with evaluations conducted every three years. Within the whole cohort of offspring, MDE (Hazard Ratio=4.44; 95%CI: 2.19-9.02), CD (HR=3.31;1.55-7.07) and DUD (HR=2.54; 1.15-5.59) predicted the onset of (hypo)manic episodes, whereas MDD in offspring was predicted by SAD (HR=1.53; 1.09-2.15), generalized anxiety (HR=2.56; 1.05-6.24), and panic disorder (HR=3.13; 1.06-9.23). The early predictors of (hypo)mania in the whole cohort were also significantly associated with the onset of (hypo)mania among the offspring of parents with BPD. The onset of mood disorders is frequently preceded by identifiable depressive episodes and nonmood disorders. These precursors differed by mood subtype in offspring. High-risk offspring with these precursors should be closely monitored to prevent the further development of MDD or conversion to BPD.

Traumatic experiences, family functioning, and mood disorder development in bipolar offspring.

ObjectivesStudies in children of patients affected with bipolar disorder (BD; bipolar offspring) are at high risk to develop mood disorders. Our aim is to investigate how environmental factors such as childhood trauma and family functioning relate to the development of mood disorders in offspring at familial risk for BD.DesignThe current study is part of a longitudinal prospective cohort study among offspring of parents with BD.MethodsThe current study is part of the Dutch Bipolar Offspring Study, an ongoing prospective cohort study among adolescent offspring of a parent with BD. Bipolar offspring were psychiatrically evaluated at baseline and at 1‐, 5‐, and 12‐year follow‐up. Complete follow‐up data over de 12‐year follow‐up were available for 102 offspring. Childhood trauma was measured with the Childhood Trauma Questionnaire (CTQ) and filled out by the offspring. Family functioning was reported by the mother with the 130‐item Questionnaire for Family Problems (QFP).ResultsEmotional maltreatment was significantly associated (HR = 1.82, CI 1.18–2.82, p = .007) with mood disorder onset in bipolar offspring. No association was found with the family functioning total score (HR = 1.04, CI 0.94–15, p = .085) nor its subscales.ConclusionsThe current study suggests that emotional maltreatment is associated with mood disorder development in bipolar offspring. Remarkably, the association of offspring‐reported emotional maltreatment and mood disorder onset was not reflected in parent‐reported family functioning (e.g., support and communication, openness or involvement). Possible explanations are discussed and warrant further study.Practitioner points Offspring of bipolar patients are at increased risk of developing mood disorders across the life‐time.Emotional trauma contributes to the likelihood of developing mood disorders in bipolar offspring.In the daily treatment of bipolar patients having children, attention should be given to parental style and difficulties.Further research using multiple informant methods on childhood trauma an family functioning is needed to further disentangle the effects of these variables on the onset of psychopathology in bipolar offspring.

Origins and Impact of Psychological Traits in Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) exhibit compromised psychiatric health. Independent of obesity, women with PCOS are more susceptible to have anxiety and depression diagnoses and other neuropsychiatric disorders. During pregnancy women with PCOS display high circulating androgen levels that may cause prenatal androgen exposure affecting the growing fetus and increasing the risk of mood disorders in offspring. Increasing evidence supports a non-genetic, maternal contribution to the development of PCOS and anxiety disorders in the next generation. Prenatal androgenized rodent models reflecting the anxiety-like phenotype of PCOS in the offspring, found evidence for the altered placenta and androgen receptor function in the amygdala, together with changes in the expression of genes associated with emotional regulation and steroid receptors in the amygdala and hippocampus. These findings defined a previously unknown mechanism that may be critical in understanding how maternal androgen excess can increase the risk of developing anxiety disorders in daughters and partly in sons of PCOS mothers. Maternal obesity is another common feature of PCOS causing an unfavorable intrauterine environment which may contribute to psychiatric problems in the offspring. Whether environmental factors such as prenatal androgen exposure and obesity increase the offspring’s susceptibility to develop psychiatric ill-health will be discussed.

The Impact of Parental and Familial Factors on the Onset of Mood Disorders in Offspring

The Impact of Parental and Familial Factors on the Onset of Mood Disorders in Offspring

2.1 Emerging Course of Major Mood Disorders in Offspring of Parents With Bipolar Disorder: Differences Associated With Parental Lithium Response

2.1 Emerging Course of Major Mood Disorders in Offspring of Parents With Bipolar Disorder: Differences Associated With Parental Lithium Response

Maternal testosterone exposure increases anxiety-like behavior and impacts the limbic system in the offspring

During pregnancy, women with polycystic ovary syndrome (PCOS) display high circulating androgen levels that may affect the fetus and increase the risk of mood disorders in offspring. This study investigated whether maternal androgen excess causes anxiety-like behavior in offspring mimicking anxiety disorders in PCOS. The PCOS phenotype was induced in rats following prenatal androgen (PNA) exposure. PNA offspring displayed anxiety-like behavior in the elevated plus maze, which was reversed by flutamide [androgen receptor (AR) blocker] and tamoxifen [selective estrogen receptor (ER) modulator]. Circulating sex steroids did not differ between groups at adult age. The expression of serotonergic and GABAergic genes associated with emotional regulation in the amygdala was consistent with anxiety-like behavior in female, and partly in male PNA offspring. Furthermore, AR expression in amygdala was reduced in female PNA offspring and also in females exposed to testosterone in adult age. To determine whether AR activation in amygdala affects anxiety-like behavior, female rats were given testosterone microinjections into amygdala, which resulted in anxiety-like behavior. Together, these data describe the anxiety-like behavior in PNA offspring and adult females with androgen excess, an impact that seems to occur during fetal life, and is mediated via AR in amygdala, together with changes in ERα, serotonergic, and GABAergic genes in amygdala and hippocampus. The anxiety-like behavior following testosterone microinjections into amygdala demonstrates a key role for AR activation in this brain area. These results suggest that maternal androgen excess may underpin the risk of developing anxiety disorders in daughters and sons of PCOS mothers.

Early exposure to parental bipolar disorder and risk of mood disorder: the Flourish Canadian prospective offspring cohort study.

Exposure to postnatal parental depression is associated with offspring mood disorder later in life; however, little is known about exposure to parental bipolar disorder (BD) and subsequent risk of psychopathology. The aim of this study was to determine the association between the duration, severity and timing of exposure to parental BD in early childhood and subsequent risk of mood disorder. 189 offspring of a parent with BD completed annual assessments following Kiddie Schedule for Affective Disorders (KSADS) format semistructured interviews as part of an ongoing 16-year prospective cohort study. Clinical data from the affected parents were collected over the first decade of their offspring's life using SADS-L format semistructured interviews and coded using the Affective Morbidity Index (AMI). A longer duration of exposure to parental BD was associated with a 1.5-fold risk of any psychopathology (95% confidence interval (CI): 1.0-2.3) and a 2.5-fold increased risk of substance use disorders (95% CI: 1.2-5.3). Exposure during the first 2 years of life was significantly associated with the risk of mood disorder (hazard ratio (HR): 1.1, 95% CI: 1.0-1.2), whereas exposure later in childhood was not. The duration of exposure to active parental BD in childhood is an important risk factor for the subsequent development of mood and non-mood psychopathology risk in offspring. These findings emphasize the importance of effective treatment of parents with BD to help both themselves and their children, especially early in development.

Prevention of Bipolar and Depressive Disorders: is This an Attainable Goal?

Despite therapeutic advances, unipolar depression and bipolar disorder are among the most debilitating psychiatric disorders. Unfortunately, lacking knowledge about the underlying pathophysiology limit early identification and indicated prevention efforts. Therefore, early characterization of the ‘prodromal” (subsyndromal) stages of depression and, especially, bipolar mania have attracted increasing attention, especially in youth, given the early age of first depression and bipolar disorder symptom onset. Review of phenomenological manifestations of the prodromal stages preceding syndromal unipolar depression and bipolar disorder, including antecedent and comorbid conditions. While offspring mood disorder studies are ongoing, clinical ‘high-risk” mood disorder research is relatively new. So far, retrospective and early prospective data suggest that a clinical prodrome exits in a sizeable patient group of patients subsequently developing unipolar depression and bipolar disorder. Moreover, phenomenologically, the early clinical depression or mania prodrome includes character traits that may become more pronounced, non-specific symptoms of decreasing role and social functioning, as well as subthreshold depressive and/or attenuated (hypo)mania-like symptoms (especially mood swings/lability, racing thoughts and sleep abnormalities). Frequent comorbidities that overlap with mood disorder criteria, the fact that several concurrent supratheshold symptoms can coexist that are still subthreshold for the full mood disorder and the episodicity of emerging as well as full mood symptoms are complicate the identification of the mood disorder prodrome. Data suggest that a relevant proportion of patients ultimately developing unipolar depression or bipolar disorder presents with a clinically identifiable depressive or (hypo)mania ‘prodromal” symptom stage that may enable indicated prevention. Prospective clinical and biological risk marker studies, utilizing specific instruments that target at-risk phenomenology are needed to advance the clinical high-risk and prevention approach for mood disorders.

Familial pathways to early-onset suicide attempt: a 5.6-year prospective study.

Suicide attempts are strong predictors of suicide, a leading cause of adolescent mortality. Suicide attempts are highly familial, although the mechanisms of familial transmission are not understood. Better delineation of these mechanisms could help frame potential targets for prevention. To examine the mechanisms and pathways by which suicidal behavior is transmitted from parent to child. In this prospective study conducted from July 15, 1997, through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age, 17.7 years) of 334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a suicide attempt, were followed up for a mean of 5.6 years. The primary outcome was a suicide attempt. Variables were examined at baseline, intermediate time points, and the time point proximal to the attempt. Participants were assessed by structured psychiatric assessments and self-report and by interview measures of domains hypothesized to be related to familial transmission (eg, mood disorder and impulsive aggression). Among the 701 offspring, 44 (6.3%) had made a suicide attempt before participating in the study, and 29 (4.1%) made an attempt during study follow-up. Multivariate logistic regression revealed that proband suicide attempt was a predictor of offspring suicide attempt (odds ratio [OR], 4.79; 95% CI, 1.75-13.07), even controlling for other salient offspring variables: baseline history of mood disorder (OR, 4.20; 95% CI, 1.37-12.86), baseline history of suicide attempt (OR, 5.69; 95% CI, 1.94-16.74), and mood disorder at the time point before the attempt (OR, 11.32; 95% CI, 2.29-56.00). Path analyses were consistent with these findings, revealing a direct effect of proband attempt on offspring suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive aggression as a precursor of mood disorder. Parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting for the familial transmission of mood disorder. Interventions that target mood disorder and impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal behavior.

Family functioning in the context of parental bipolar disorder: associations with offspring age, sex, and psychopathology.

Previous research has shown that families with a parent who has bipolar disorder (BD) may experience family functioning difficulties. However, the association between family functioning and psychopathology among offspring of parents with BD, and offspring characteristics that may moderate this association, remains poorly understood. This study examined the cross-sectional associations between family functioning (cohesion, expressiveness, and conflict) and psychopathology in 117 offspring (ages 5-18) of 75 parents with BD. We also examined whether age and sex differences moderated these associations. We measured offspring psychopathology by examining current dimensional symptoms and DSM-IV emotional and behavioral disorders. Correlational analyses indicated that higher family conflict and lower cohesion were associated with higher internalizing and externalizing symptoms in offspring. Lower family cohesion was also associated with current offspring mood disorders. Moderation analyses indicated, first, that the link between lower family cohesion and internalizing symptoms was stronger for younger offspring compared to older offspring. Second, higher family conflict and current mood disorder were associated in younger males but not in older males or in females. Results remained the same after controlling for parental anxiety or substance use disorder comorbidity. Our study highlights the importance of accounting for family functioning when working with offspring at risk for BD, while also recognizing that the connections between family functioning and offspring outcomes are complex and differ based on offspring sex and developmental stage.

Early parent-child relationships and risk of mood disorder in a Canadian sample of offspring of a parent with bipolar disorder: findings from a 16-year prospective cohort study.

Exposure to parental bipolar disorder (BD) early in life may increase the risk of developing a mood disorder. However, the impact of early parent-child relationships when a parent is affected and how this impacts an offspring's risk remains unclear. The primary objective of this study was to determine the association between parent-child relationships and risk of mood disorder in offspring of parents with BD and, secondly, to determine the interaction of temperament and life stress on this association. Two hundred and thirty-three offspring completed annual clinical assessments following Kiddie Schedule for Affective Disorders (KSADS) format interviews as part of an ongoing Canadian prospective cohort study conducted from 1996 to 2013. Offspring completed measures of early adversity, life stress and temperament. Clinical data from the affected parents were prospectively collected over the first decade of their offspring's life using SADS format interviews. Higher perceived neglect from mother and offspring emotionality were significantly associated with the hazard of mood disorder (hazard ratio (HR): 1.1, 95% confidence interval (CI): 1.0-1.2 and HR: 1.7, 95% CI: 1.0-3.1, respectively). Duration of exposure to parental BD significantly interacted with offspring emotionality to predict mood disorder (P = 0.01). Further, perceived neglect from mother was associated with offspring high emotionality (P = 0.02). Neglect from mother is a significant early predictor of mood disorder in offspring at familial risk for BD and may increase emotional sensitivity. Psychosocial support and interventions for high-risk families could be beneficial in reducing early adversity, maternal neglect and the risk of subsequent mood disorders in offspring.

Childhood anxiety: An early predictor of mood disorders in offspring of bipolar parents

BackgroundAnxiety disorders are common among the offspring of parents with bipolar disorder (BD). This study investigated the nature of the association between anxiety disorders and mood disorders in a prospectively studied high-risk cohort. MethodsHigh-risk offspring were identified from families in which one parent had confirmed BD based on SADS-L interviews and best estimate diagnostic procedures. All agreeable offspring aged 8–25 years were enrolled in a longitudinal study involving repeated KSADS-PL format clinical assessments. Control (C) offspring from families in which neither parent met lifetime criteria for a psychiatric disorder were similarly assessed. All DSM-IV diagnoses in the offspring were confirmed on blind consensus review. Cumulative incidence and adjusted Cox Proportional Hazards models were used to calculate the risk of anxiety disorders and the predictive association with mood disorders. ResultsThe cumulative incidence of anxiety disorders was higher (23.40% vs. 10.42%; HR=2.136; p=.0382) and occurred earlier (9.79 vs. 14.84 years; p=.0125) in high-risk compared to C offspring. In high-risk offspring generalized anxiety disorders (GAD) followed by social phobia were the most incident anxiety subtypes; while high emotionality (HR 1.111; p=.0096) and shyness (HR 1.144; p=.0053) increased the risk of anxiety disorders. Anxiety disorders increased the adjusted risk of mood disorders (HR 2.166; p=.0004), on average 8.49 years later (SD 5.97). LimitationsThe cumulative incidence of BD is relatively low, as the cohort is still in the period of risk. ConclusionsFindings highlight the need for longitudinal surveillance of symptomatic high-risk children and suggest anxiety disorders are an important early intervention target.

Faster progression from smoking initiation to heavy smoking mediates polygenic risk for adult smoking problems

The number of ancestors with anxiety, depressive and substance use disorders reflects the multigenerational morbidity load of psychopathology. Results: After adjusting for familial load of other psychopathology, the incidence for anxiety disorders among offspring significantly increased across age (using Cox regression) with higher familial load of anxiety (HR= 1.17) and substance use disorders (HR=1.15). The cumulative incidence for offspring mood disorders was significantly higher the more ancestors were affected by mood (HR=1.29) and substance use disorders (HR=1.15). Substance use disorder risk among offspring increased with higher familial load of substance use disorders (HR=1.37). Discussion:Our findings are in line with prior research suggesting familiality in anxiety, mood and substance use disorders and emphasize an important role of familial morbidity load. A familial history of substance use disorders appears particularly critical because of evidence for cross-transmission to anxiety and mood disorders beyond the effects of homotypic comorbidity.

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-1390 - Prenatal stress and affective disorders in a population birth cohort

Maternal psychological stress during pregnancy has been associated with the risk for mood disorders in offspring, although there is no consensus about the influence of the timing of the stress on outcomes. We examined the relationship of prenatal stress at specific times in pregnancy to the incidence of mood disorders in offspring using data from a large birth cohort. We linked data on 90,079 offspring born in Jerusalem in 1964–76 to Israel's psychiatric registry. We used proportional hazards models to evaluate the link between discharge diagnoses and gestational age during the Arab-Israeli war of June, 1967. Those in their first trimester of fetal development during the war were significantly more likely to be admitted to hospitals for any mood disorders (RR = 3.01, 1.68–5.39, p = .0002), and the subgroups of bipolar disorder (2.44; 1.0–5.99; p = .054) and “other” mood disorders (3.61; 1.68–7.80; p = .001). Mood disorders were substantially increased in offspring whose mothers had been in the third month of pregnancy in June, 1967 (5.54, 2.73–11.24, p < .0001). These findings suggest that acute maternal stress in early pregnancy may contribute to the etiology of mood disorders in offspring. They point to the third month of fetal development as a moment of special vulnerability.