Daily and weekly mood ratings using a remote capture method in high-risk offspring of bipolar parents: Compliance and symptom monitoring.

OBJECTIVES: To determine the compliance and clinical utility of weekly and daily electronic mood symptom monitoring in adolescents and young adults at risk for mood disorder. METHODS: Fifty emerging adult offspring of bipolar parents were recruited from the Flourish Canadian high-risk offspring cohort study along with 108 university student controls. Participants were assessed by KSADS/SADS-L semi-structured interviews and used a remote capture method to complete weekly and daily mood symptom ratings using validated scales for 90 consecutive days. Hazard models and generalized estimating equations were used to determine differences in summary scores and regularity of ratings. RESULTS: Seventy-eight and 77% of high-risk offspring and 97% and 93% of controls completed the first 30 days of weekly and daily ratings, respectively. There were no differences in drop-out rates between groups over 90 days (weekly P = 0.2149; daily P = 0.9792). There were no differences in mean summary scores or regularity of weekly anxiety, depressive or hypomanic symptom ratings between high-risk offspring and control groups. However, high-risk offspring compared to controls had daily ratings indicating lower positive affect, higher negative affect and lower self-esteem (P = 0.0317). High-risk offspring with remitted mood disorder compared to those without had more irregularity in weekly anxiety and depressive symptom ratings and daily ratings of lower positive affect, higher negative affect, and higher shame and self-doubt (P = 0.0365). CONCLUSIONS: Findings support that high-resolution electronic mood tracking may be a feasible and clinically useful approach in monitoring emerging psychopathology in young people at high-risk offspring of mood disorder onset or recurrence.

Exponential decay for binary time-varying covariates in Cox models.

Cox models are commonly used in the analysis of time to event data. One advantage of Cox models is the ability to include time-varying covariates, often a binary covariate that codes for the occurrence of an event that affects an individual subject. A common assumption in this case is that the effect of the event on the outcome of interest is constant and permanent for each subject. In this paper, we propose a modification to the Cox model to allow the influence of an event to exponentially decay over time. Methods for generating data using the inverse cumulative density function for the proposed model are developed. Likelihood ratio tests and AIC are investigated as methods for comparing the proposed model to the commonly used permanent exposure model. A simulation study is performed, and 3 different data sets are presented as examples.

The developmental trajectory of bipolar disorder.

BACKGROUND: Bipolar disorder is highly heritable and therefore longitudinal observation of children of affected parents is important to mapping the early natural history. AIMS: To model the developmental trajectory of bipolar disorder based on the latest findings from an ongoing prospective study of the offspring of parents with well-characterised bipolar disorder. METHOD: A total of 229 offspring from families in which 1 parent had confirmed bipolar disorder and 86 control offspring were prospectively studied for up to 16 years. High-risk offspring were divided into subgroups based on the parental long-term response to lithium. Offspring were clinically assessed and DSM-IV diagnoses determined on masked consensus review using best estimate procedure. Adjusted survival analysis and generalised estimating equations were used to calculate differences in lifetime psychopathology. Multistate models were used to examine the progression through proposed clinical stages. RESULTS: High-risk offspring had an increased lifetime risk of a broad spectrum of disorders including bipolar disorder (hazard ratio (HR) = 20.89; P = 0.04), major depressive disorder (HR = 17.16; P = 0.004), anxiety (HR = 2.20; P = 0.03), sleep (HR = 28.21; P = 0.02) and substance use disorders (HR = 2.60; P = 0.05) compared with controls. However, only offspring from lithium non-responsive parents developed psychotic disorders. Childhood anxiety disorder predicted an increased risk of major mood disorder and evidence supported a progressive transition through clinical stages, from non-specific psychopathology to depressive and then manic or psychotic episodes. CONCLUSIONS: Findings underscore the importance of a developmental approach in conjunction with an appreciation of familial risk to facilitate earlier accurate diagnosis in symptomatic youth.

Predictors of leisure time physical activity among people with spinal cord injury.

BACKGROUND: Most studies of physical activity predictors in people with disability have lacked a guiding theoretical framework. Identifying theory-based predictors is important for developing activity-enhancing strategies. PURPOSE: To use the World Health Organization's International Classification of Functioning, Disability and Health (ICF) framework to identify predictors of leisure time physical activity among people with spinal cord injury (SCI). METHODS: Six hundred ninety-five persons with SCI (M age=47; 76% male) completed measures of Body Functions and Structures, Activities and Participation, Personal Factors, and Environmental Factors at baseline and 6-months. Activity was measured at 6 and 18 months. Logistic and linear regression models were computed to prospectively examine predictors of activity status and activity minutes per day. RESULTS: Models explained 19%-25% of variance in leisure time physical activity. Activities and Participation and Personal Factors were the strongest, most consistent predictors. CONCLUSIONS: The ICF framework shows promise for identifying and conceptualizing predictors of leisure time physical activity in persons with disability.

A likelihood approach to estimating animal density from binary acoustic transects.

We propose an approximate maximum likelihood method for estimating animal density and abundance from binary passive acoustic transects, when both the probability of detection and the range of detection are unknown. The transect survey is purposely designed so that successive data points are dependent, and this dependence is exploited to simultaneously estimate density, range of detection, and probability of detection. The data are assumed to follow a homogeneous Poisson process in space, and a second-order Markov approximation to the likelihood is used. Simulations show that this method has small bias under the assumptions used to derive the likelihood, although it performs better when the probability of detection is close to 1. The effects of violations of these assumptions are also investigated, and the approach is found to be sensitive to spatial trends in density and clustering. The method is illustrated using real acoustic data from a survey of sperm and humpback whales.

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

BACKGROUND: Bipolar 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. RESULTS: Overall, 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. CONCLUSIONS: This 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.

Development and validation of a risk calculator for major mood disorders among the offspring of bipolar parents using information collected in routine clinical practice.

BACKGROUND: Family history is a significant risk factor for bipolar disorders (BD), but the magnitude of risk varies considerably between individuals within and across families. Accurate risk estimation may increase motivation to reduce modifiable risk exposures and identify individuals appropriate for monitoring over the peak risk period. Our objective was to develop and independently replicate an individual risk calculator for bipolar spectrum disorders among the offspring of BD parents using data collected in routine clinical practice. METHODS: Data from the longitudinal Canadian High-Risk Offspring cohort study collected from 1996 to 2020 informed the development of a 5 and 10-year risk calculator using parametric time-to-event models with a cure fraction and a generalized gamma distribution. The calculator was then externally validated using data from the Lausanne-Geneva High-Risk Offspring cohort study collected from 1996 to 2020. A time-varying C-index by age in years was used to estimate the probability that the model correctly classified risk. Bias corrected estimates and 95% confidence limits were derived using a jackknife resampling approach. FINDINGS: The primary outcome was age of onset of a major mood disorder. The risk calculator was most accurate at classifying risk in mid to late adolescence in the Canadian cohort (n = 285), and a similar pattern was replicated in the Swiss cohort (n = 128). Specifically, the time-varying C-index indicated that there was approximately a 70% chance that the model would correctly predict which of two 15-year-olds would be more likely to develop the outcome in the future. External validation within a smaller Swiss cohort showed mixed results. INTERPRETATION: Findings suggest that this model may be a useful clinical tool in routine practice for improved individualized risk estimation of bipolar spectrum disorders among the adolescent offspring of a BD parent; however, risk estimation in younger high-risk offspring is less accurate, perhaps reflecting the evolving nature of psychopathology in early childhood. Based on external validation with a Swiss cohort, the risk calculator may not be as predictive in more heterogenous high-risk populations. FUNDING: The Canadian High-Risk Study has been funded by consecutive operating grants from the Canadian Institutes for Health Research, currently CIHR PJT Grant 152796 he Lausanne-Geneva high-risk study was and is supported by five grants from the Swiss National Foundation (#3200-040,677, #32003B-105,969, #32003B-118,326, #3200-049,746 and #3200-061,974), three grants from the Swiss National Foundation for the National Centres of Competence in Research project "The Synaptic Bases of Mental Diseases" (#125,759, #158,776, and #51NF40 - 185,897), and a grant from GlaxoSmithKline Clinical Genetics.

The role of emotional abuse in intimate partner violence and health among women in Yokohama, Japan.

OBJECTIVES: As part of the World Health Organization's cross-national research effort, we investigated the relationship between various health indicators and the experience of intimate partner violence (IPV), which included emotional, physical, and sexual abuse, among women in Yokohama, Japan. METHODS: We used multivariate logistic and negative binomial regression to examine the relationship between health status and IPV in a stratified cluster sample of 1371 women aged 18 to 49 years. RESULTS: In 9 of 11 health indicators examined, the odds of experiencing health-related problems were significantly higher (P < .05) among those that reported emotional abuse plus physical or sexual violence than among those that reported no IPV, after we controlled for sociodemographic factors, childhood sexual abuse, and adulthood sexual violence perpetrated by someone other than an intimate partner. For most health indicators, there were no significant differences between those that reported emotional abuse only and those that reported emotional abuse plus physical or sexual violence. CONCLUSIONS: The similarity of outcomes among those that reported emotional abuse only and those that reported emotional abuse plus physical or sexual violence suggests the need for increased training of health care providers about the effects of emotional abuse.

CD56bright cells increase expression of {alpha}4 integrin at ovulation in fertile cycles.

Leukocyte content of human endometrium changes rapidly after ovulation, particularly as a result of gains in CD56(bright) uterine NK (uNK) cells. We have proposed that uNK precursor cells are found within the blood CD56(bright) pool and are recruited to decidualizing endometrium through functional changes in their adhesion molecules and chemokine receptors. This study sought to quantify alterations in adhesion molecules, cytokines, chemokines, and receptors induced in circulating CD56(+) cells of fertile and infertile women by ovulation. Blood was drawn from 12 fertile volunteers and six female-infertility patients at Menstrual Cycle Day (d) 5 and on the day following the preovulatory surge of luteinizing hormone (LH). CD56(bright), CD56(dim), and CD56(+)CD3(+) cell subsets were isolated and evaluated by flow cytometry, quantitative PCR, or Western blotting. In CD56(bright) cells from fertile but not infertile women, alpha(4) integrin increased between d5 and the preovulatory LH surge. CD56(dim) and NKT cells did not show a change in alpha(4) integrin but differed significantly between fertile and infertile donors, and infertile donors had reduced homing molecule expression in CD56(dim) and NKT cells, and at ovulation, their NKT cells showed elevated cytokine production. None of the circulating CD56(+) cell subsets had transcripts for receptors for estrogen, progesterone, LH, or prolactin. Thus, immunological events associated with the LH surge induce alterations in all subsets of CD56(+) cells, and the unique induction of alpha(4) integrin in CD56(bright) cells of fertile women constitutes a potential method to promote uterine homing.

Creating case scenarios or vignettes using factorial study design methods.

AIM: This paper is a report of a study conducted to develop clinical case vignettes using an adaptation of an incomplete factorial study design methodology. BACKGROUND: In health care, vignettes or cases scenarios are core to problem-based learning, common in practice guideline development processes, and increasingly being used in patient or care-giver studies of chronic or life-threatening illnesses. A large number of behavioural, psycho-social and clinical factors can be relevant in such decision problems. Unbiased methods for choosing what factors to include are needed, when it is not possible to include all relevant combinations of factors in the vignettes. METHOD: The factors to be considered, number of levels or categories for each factor, and desired number of scenarios were decided in advance. An algorithm was used first to create the full factorial data set, and then a random subset of combinations was generated, according to predefined criteria, based on maximizing determinants. The subset of combinations was incorporated into written vignettes. The study was conducted in 2004-2005. FINDINGS: Application of the method yielded diverse and balanced scenarios that covered the full range of factors to be considered for a project to elicit health providers' processes in diet counselling for dyslipidemia. CONCLUSION: The approach is flexible, decreases possible researcher bias in the creation of vignettes, and can improve statistical power in survey research. This novel application of study design methodology merits consideration when vignettes are being developed to elicit opinions or decisions in studies of complex health issues.

Investigating the association between anxiety symptoms and mood disorder in high-risk offspring of bipolar parents: a comparison of Joint and Cox models.

BACKGROUND: Anxiety is associated with mood disorders including bipolar disorder. Two statistical modelling frameworks were compared to investigate the longitudinal relationship between repeatedly measured anxiety symptoms and the onset of depression and bipolar disorder in youth at confirmed familial risk. METHODS: Prospectively collected data on 156 offspring of a parent with confirmed bipolar disorder participating in the Canadian Flourish high-risk offspring longitudinal cohort study were used for this analysis. As part of the research protocol at approximately yearly visits, a research psychiatrist completed the HAM-A and a semi-structured diagnostic research interview following KSADS-PL format. Diagnoses using DSM-IV criteria were made on blind consensus review of all available clinical information. We investigated two statistical approaches, Cox model and Joint model, to evaluate the relationship between repeated HAM-A scores and the onset of major depressive or bipolar disorder. The Joint model estimates the trajectory of the longitudinal variable using a longitudinal sub-model and incorporates this estimated trajectory into a Cox sub-model. RESULTS: There was evidence of an increased hazard of major mood disorder for high-risk individuals with higher HAM-A scores under both modelling frameworks. After adjusting for other covariates, a one-unit increase in log-transformed HAM-A score was associated with a hazard ratio of 1.74 (95% CI (1.12, 2.72)) in the Cox model compared to 2.91(95% CI (1.29, 6.52)) in the Joint model. In an exploratory analysis there was no evidence that family clustering substantially affected the conclusions. CONCLUSIONS: Estimated effects from the conventional Cox model, which is often the model of choice, were dramatically lower in this dataset, compared to the Joint model. While the Cox model is often considered the approach of choice for analysis, research has shown that the Joint model may be more efficient and less biased. Our analysis based on a Joint model suggests that the magnitude of association between anxiety and mood disorder in individuals at familial risk of developing bipolar disorder may be stronger than previously reported.

Epigenetic markers in inflammation-related genes associated with mood disorder: a cross-sectional and longitudinal study in high-risk offspring of bipolar parents.

Bipolar disorder is highly heritable and typically onsets in late adolescence or early adulthood. Evidence suggests that immune activation may be a mediating pathway between genetic predisposition and onset of mood disorders. Building on a prior study of mRNA and protein levels in high-risk offspring published in this Journal, we conducted a preliminary examination of methylation profiles in candidate immune genes from a subsample of well-characterized emergent adult (mean 20 years) offspring of bipolar parents from the Canadian Flourish high-risk cohort. Models were adjusted for variable age at DNA collection, sex and antidepressant and mood stabilizer use. On cross-sectional analysis, there was evidence of higher methylation rates for BDNF-1 in high-risk offspring affected (n = 27) and unaffected (n = 23) for mood disorder compared to controls (n = 24) and higher methylation rates in affected high-risk offspring for NR3C1 compared to controls. Longitudinal analyses (25 to 34 months) provided evidence of steeper decline in methylation rates in controls (n = 24) for NR3C1 compared to affected (n = 15) and unaffected (n = 11) high-risk offspring and for BDNF-2 compared to affected high-risk. There was insufficient evidence that changes in any of the candidate gene methylation rates were associated with illness recurrence in high-risk offspring. While preliminary, findings suggest that longitudinal investigation of epigenetic markers in well-characterized high-risk individuals over the peak period of risk may be informative to understand the emergence of bipolar disorder.

U-Flourish university students well-being and academic success longitudinal study: a study protocol.

INTRODUCTION: Over 30% of Canadians between the ages of 16 and 24 years attend university. This period of life coincides with the onset of common mental illnesses. Yet, data to inform university-based mental health prevention and early intervention initiatives are limited. The U-Flourish longitudinal study based out of Queen's University, Canada and involving Oxford University in the UK, is a student informed study funded by the Canadian Institute for Health Research Strategy for Patient Oriented Research (CIHR-SPOR). The primary goal of U-Flourish research is to examine the contribution of risk and resiliency factors to outcomes of well-being and academic success in first year students transitioning to university. METHODS AND ANALYSIS: The study is a longitudinal survey of all first-year undergraduate students entering Queen's University in the fall term of 2018 (and will launch at Oxford University in fall of 2019). In accordance with the CIHR-SPOR definitions, students represent the target population (ie, patient equivalent). Student peer health educators were recruited to inform the design, content and implementation of the study. Baseline surveys of Queen's first year students were completed in the fall of 2018, and follow-up surveys at the end of first year in the spring of 2019. Extensive student-led engagement campaigns were used to maximise participation rates. The baseline survey included measures of personal factors, family factors, environmental factors, psychological and emotional health, and lifestyle factors. Main outcomes include self-reported indicators of mental health at follow-up and mental health service access, as well as objective measures of academic success through linkage to university administrative and academic databases. A combination of mixed effects regression techniques will be employed to determine associations between baseline predictive factors and mental health and academic outcomes. ETHICS AND DISSEMINATION: Ethical approval was obtained by the Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (HSREB) (#6023126) at Queen's University. Findings will be disseminated through international and national peer-reviewed scientific articles and other channels including student-driven support and advocacy groups, newsletters and social media.

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

AIM: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Experiences of intimate partner violence and related injuries among women in Yokohama, Japan.

We estimated rates of intimate partner violence and related injuries in a sample of 1371 women aged 18 to 49 years in Yokohama, Japan. By the age of 30 years, 14.3% of women who had ever had a partner had experienced violence from that partner, and 3.3% had suffered injuries related to such violence. By the time women had reached the age of 49 years, these percentages were 19% and 4%, respectively. In addition to the need for increased prevention efforts, our findings indicate the need for an expanded legal definition of intimate partner violence in Japan given that the current definition excludes premarital violence.

Demographic determinants of acute gastrointestinal illness in Canada: a population study.

BACKGROUND: Gastrointestinal illness is an important global public health issue, even in developed countries, where the morbidity and economic impact are significant. Our objective was to evaluate the demographic determinants of acute gastrointestinal illness in Canadians. METHODS: We used data from two population-based studies conducted in select communities between 2001 and 2003. Together, the studies comprised 8,108 randomly selected respondents; proxies were used for all respondents under 12 years and for respondents under 19 years at the discretion of the parent or guardian. Using univariate and multivariate logistic regression, we evaluated the following demographic determinants: age, gender, cultural group, and urban/rural status of the respondent, highest education level of the respondent or proxy, number of people in the household, and total annual household income. Two-way interaction terms were included in the multivariate analyses. The final multivariate model included income, age, gender, and the interaction between income and gender. RESULTS: After adjusting for income, gender, and their interaction, children under 10 years had the highest risk of acute gastrointestinal illness, followed by young adults aged 20 to 24 years. For males, the risk of acute gastrointestinal illness was similar across all income levels, but for females the risk was much higher in the lowest income category. Specifically, in those with total annual household incomes of less than $20,000, the odds of acute gastrointestinal illness were 2.46 times higher in females than in males. CONCLUSION: Understanding the demographic determinants of acute gastrointestinal illness is essential in order to identify vulnerable groups to which intervention and prevention efforts can be targeted.

Energy dispersive X-ray diffraction as a means to identify illicit materials: a preliminary optimisation study.

Energy dispersive X-ray diffraction is proposed as a suitable non-destructive method to rapidly identify illicit drugs in parcels. A preliminary data set of 7 illicit drug samples and a possible cutting agent has been collected with a range of count times using a tungsten target X-ray source, a high resolution HpGe detector and a variable geometry diffraction cell. These results have been used to calibrate and train multivariate analysis software to predict the drug content in previously unseen spectra.

Repeated salivary daytime cortisol and onset of mood episodes in offspring of bipolar parents.

BACKGROUND: Differences in cortisol secretion may differentiate individuals at high compared to low genetic risk for bipolar disorder (BD) and predict the onset or recurrence of mood episodes. The objectives of this study were to determine if salivary cortisol measures are: (1) different in high-risk offspring of parents with BD (HR) compared to control offspring of unaffected parents (C), (2) stable over time, (3) associated with the development of mood episode onset/recurrence, and (4) influenced by comorbid complications. METHODS: Fifty-three HR and 22 C completed salivary cortisol sampling annually for up to 4 years in conjunction with semi-structured clinical interviews. The cortisol awakening response (CAR), daytime cortisol [area under the curve (AUC)], and evening cortisol (8:00 p.m.) were calculated. RESULTS: There were no differences in baseline CAR, AUC and evening cortisol between HR and C (p = 0.38, p = 0.30 and p = 0.84), respectively. CAR, AUC and evening cortisol were stable over yearly assessments in HR, while in Cs, evening cortisol increased over time (p = 0.008), and CAR and AUC remained stable. In HR, AUC and evening cortisol increased the hazard of a new onset mood disorder/recurrence by 2.7 times (p = 0.01), and 3.5 times (p = 0.01), respectively, but this was no longer significant after accounting for multiple comparisons. CONCLUSIONS: Salivary cortisol is stable over time within HR offspring. However, between individuals, basal salivary cortisol is highly variable. More research is needed, with larger samples of prospectively studied HR youth using a more reliable method of cortisol measurement, to determine the potential role of cortisol in the development of mood disorders.

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.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.