The Resilient Youth Program: a promising skills-based online program for resiliency and stress management.

BACKGROUND: Prevention programs that target resilience may help youth address mental health difficulties and promote well-being during public health crises. AIMS: To examine the preliminary efficacy of the Resilient Youth Program (RYP). METHOD: The RYP was delivered remotely from a US academic medical centre to youth in the community via a naturalistic pilot study. Data from 66 youth (ages 6-18, Mage = 11.65, SD = 3.02) and their parents were collected via quality assurance procedures (May 2020 to March 2021). Pre/post-intervention child/parent-reported psychological and stress symptoms as well as well-being measures were compared via Wilcoxon signed rank tests. Child/parent-reported skills use data were collected. RESULTS: Among child-reported outcomes, there were significant decreases in physical stress (p = .03), anxiety (p = .004), depressive symptoms (p < .001) and anger (p = .002), as well as increased life satisfaction (p = .02). There were no significant differences in child-reported psychological stress (p = .06) or positive affect (p = .09). Among parent-reported child outcomes, there were significant decreases in psychological (p < .001) and physical stress (p = .03), anxiety (p < .001), depressive symptoms (p < .001), and anger (p < .002) as well as increased positive affect (p < .001) and life satisfaction (p < .001). Effect sizes ranged from small to medium; 77% of youth (73% of parents) reported using RYP skills. Age and gender were not associated with outcome change. CONCLUSIONS: The RYP may help reduce psychological/stress symptoms and increase well-being among youth; further research is needed.

Anxiety and Disruptive Behavior Symptoms and Disorders in Preschool-Age Offspring of Parents With and Without Bipolar Disorder: Associations With Parental Comorbidity.

OBJECTIVE: We examined the relative contribution of parental bipolar disorder (BPD) and psychiatric comorbidities (disruptive behavior disorders [DBD] and anxiety disorders) in predicting psychiatric symptoms and disorders in 2-5-year-old offspring. METHODS: Participants were 60 families with a parent with BPD and 78 offspring and 70 comparison families in which neither parent had a mood disorder and 91 offspring. Parent and offspring diagnoses and symptoms were assessed using standardized diagnostic interviews and measures, with offspring assessors masked to parental diagnoses. RESULTS: Offspring of parents with BPD had significant elevations in behavioral, mood and anxiety disorders and symptoms. Both parental BPD and DBD contributed to elevations in child disruptive behavioral symptoms, whereas child anxiety symptoms were more strongly predicted by comorbid parental anxiety. Parental BPD was a stronger predictor than comorbid DBD of child DBDs. CONCLUSION: Some of the elevated risk for disorders in preschoolers is accounted for by parental comorbidity.

Screening Infants Through Adolescents for Social/Emotional/Behavioral Problems in a Pediatric Network.

OBJECTIVE: To assess changes in screening completion in a diverse, 7-clinic network after making annual screening for social/emotional/behavioral (SEB) problems the standard of care for all infant through late adolescent-aged patients and rolling out a fully automated screening system tied to the electronic medical record and patient portal. METHODS: In 2017, the Massachusetts General Hospital made SEB screening using the age-appropriate version of the Pediatric Symptom Checklist the standard of care in its pediatric clinics for all patients aged 2.0 months to 17.9 years. Billing records identified all well-child visits between January 1, 2016 and December 31, 2019. For each visit, claims were searched for billing for an SEB screen and the electronic data warehouse was queried for an electronically administered screen. A random sample of charts was reviewed for other evidence of screening. Chi-square analyses and generalized estimating equations assessed differences in screening over time and across demographic groups. RESULTS: Screening completion (billing and/or electronic) significantly increased from 2016 (37.2%) through 2019 (2017 [46.2%] vs 2018 [66.8%] vs 2019 [70.9%]; χ2 (3) =112652.33, P < .001), with an even higher prevalence found after chart reviews. Most clinics achieved screening levels above 90% by the end of 2019. Differences among demographic groups were small and dependent on whether data were aggregated at the clinic or system level. CONCLUSIONS: Following adoption of a best-practice policy and implementation of an electronic system, SEB screening increased in all age groups and clinics. Findings demonstrate that the AAP recommendation for routine psychosocial assessment is feasible and sustainable.

Further Evidence that Subsyndromal Manifestations of Depression in Childhood Predict the Subsequent Development of Major Depression: A Replication Study in a 10 Year Longitudinally Assessed Sample.

BACKGROUND: We have previously shown that subsyndromal scores on the Child Behavior Checklist (CBCL)-Anxiety/Depression (Anx/Dep) scale at baseline predicted the subsequent development of Major Depressive Disorder (MDD) in youth with ADHD. The present study aimed to replicate these findings in a separate, long-term, longitudinal sample of children at high- and low- risk for depression. METHODS: 219 children of parents with and without depression and/or anxiety, ages 2-25, were stratified into 3 groups: 1) children with familial risk for depression (by presence of parental MDD) plus subsyndromal scores on the CBCL-Anx/Dep scale, 2) children with familial risk for depression without subsyndromal scores, and 3) children with neither familial risk for depression nor subsyndromal scores. Subjects were reassessed at both 5 and 10 year follow-ups. RESULTS: Children with both subsyndromal scores on the CBCL-Anx/Dep plus a familial risk for depression were at greater risk for developing MDD at the 10 year follow-up when compared with all other groups. Those with familial risk but no subsyndromal scores had an intermediate risk that was greater than the controls, who had the lowest risk. LIMITATIONS: The recruitment of the study included families with parental panic disorder, so the sample likely included more families with anxiety disorders than the general population. CONCLUSIONS: Our results showed that subsyndromal scores of the CBCL-Anx/Dep scale increased the risk for the subsequent development of MDD, particularly in children at high risk for depression. These results confirm the CBCL-Anx/Dep scale's utility in identifying children at high risk for developing MDD.

Risk Factors for Depression in Adolescents With ADHD: The Impact of Cognitive Biases and Stress.

Objective: Youth diagnosed with ADHD are at heightened risk of depression. However, many do not develop depression. Individuals with specific cognitive biases are more likely to develop depression yet it remains untested whether these vulnerability-stress models apply to depression risk in youth with ADHD. Method: We examined whether interpretation and attention biases moderated the relation between stressful life events and depressive symptoms in a sample of adolescents (Mage = 14.42) with ADHD (n = 59) and without ADHD (n = 36). Results: Youth with ADHD experienced more stressful life events compared with those without ADHD. Interpretation biases moderated the association between stress and depressive symptoms in youth with and without ADHD. Attention biases moderated the association between stress and depressive symptoms in the non-ADHD youth only. Conclusion: These results enhance our understanding of vulnerability for depression in adolescence with ADHD and inform targeted prevention and treatment models during this critical developmental juncture.

Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.

Exploring the stress sensitization theory with temperamentally inhibited children: a population-based study.

BACKGROUND: This study explored whether temperamentally inhibited children who experience early trauma are vulnerable to developing internalizing problems in the face of later life-stressors. METHODS: A validated screen for temperamental inhibition was distributed to parents of young children attending preschools in six government regions of Melbourne, Australia. Screening identified 11% of children as inhibited (703 of 6347 screened) and eligible for a prevention study. Participants were 545 parents of inhibited preschoolers (78% uptake), of whom 84% were followed into mid childhood (age 7-10 years: wave 1, n = 446; wave 2, n = 427; wave 3, n = 426). Parents and children then completed questionnaires for child internalizing (anxious and depressive) symptoms, and parents received a diagnostic interview for child anxiety disorder. In mid-childhood parents also completed questionnaires annually to describe recent life-stressors experienced by their child, and any potentially traumatic events in the first four years of life. RESULTS: Only one in 14 temperamentally inhibited children had experienced a potentially traumatic event in early childhood. In mid childhood 56% experienced recent life-stressors. Inhibited children who had early life trauma experienced slightly more anxiety disorder and symptoms in mid childhood. Those children with more recent life-stressors in mid childhood also had slightly more symptoms of anxiety and depression. In contrast to stress sensitization, inhibited children with early trauma plus recent stressors did not show especially high mid-childhood internalizing difficulties. CONCLUSIONS: Early life trauma and recent life-stressors each convey a small risk for children with an inhibited temperament to develop internalizing problems. Nevertheless, early life stress may not always result in negative sensitization for children in the general population.

Image acquisition and quality assurance in the Boston Adolescent Neuroimaging of Depression and Anxiety study.

The Connectomes Related to Human Diseases (CRHD) initiative was developed with the Human Connectome Project (HCP) to provide high-resolution, open-access, multi-modal MRI data to better understand the neural correlates of human disease. Here, we present an introduction to a CRHD project, the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study, which is collecting multimodal neuroimaging, clinical, and neuropsychological data from 225 adolescents (ages 14-17), 150 of whom are expected to have a diagnosis of depression and/or anxiety. Our transdiagnostic recruitment approach samples the full spectrum of depressed/anxious symptoms and their comorbidity, consistent with NIMH Research Domain Criteria (RDoC). We focused on an age range that is critical for brain development and for the onset of mental illness. This project sought to harmonize imaging sequences, hardware, and functional tasks with other HCP studies, although some changes were made to canonical HCP methods to accommodate our study population and questions. We present a thorough overview of our imaging sequences, hardware, and scanning protocol. We detail similarities and differences between this study and other HCP studies. We evaluate structural-, diffusion-, and functional-image-quality measures that may be influenced by clinical factors (e.g., disorder, symptomatology). Signal-to-noise and motion estimates from the first 140 adolescents suggest minimal influence of clinical factors on image quality. We anticipate enrollment of an additional 85 participants, most of whom are expected to have a diagnosis of anxiety and/or depression. Clinical and neuropsychological data from the first 140 participants are currently freely available through the National Institute of Mental Health Data Archive (NDA).

Family-Centered Cognitive Behavioral Therapy for Anxiety in Very Young Children with Autism Spectrum Disorder.

To address the paucity of cognitive-behavioral therapy (CBT) protocols available to treat anxiety in preschoolers with ASD, we piloted a family-centered CBT protocol in a series of 16 children aged 3-7 years with ASD and anxiety disorders and explored its feasibility and efficacy. Children were assessed at baseline, post-treatment (PT), and 4-month follow-up (FU) using diagnostic interviews and parent questionnaires. Fourteen children completed at least 10 sessions (mean 14). At PT, 81% were rated "very much-" or "much-improved" on the CGI-Anxiety. Children displayed significant decreases on clinician- and parent-rated anxiety, and improved family function and coping. Gains were maintained at FU. Parent-child CBT is feasible for young children with ASD plus anxiety that shows potential for similar efficacy as with neurotypical children.

Association of Intrinsic Brain Architecture With Changes in Attentional and Mood Symptoms During Development.

Importance: Understanding the neurodevelopmental trajectory of psychiatric symptoms is important for improving early identification, intervention, and prevention of mental disorders. Objective: To test whether the strength of the coupling of activation between specific brain regions, as measured by resting-state functional magnetic resonance imaging (fMRI), predicted individual children's developmental trajectories in terms of attentional problems characteristic of attention-deficit/hyperactivity disorder and internalizing problems characteristics of major depressive disorder (MDD). Design, Setting, and Participants: A community cohort of 94 children was recruited from Vanderbilt University between 2010 and 2013. They were followed up longitudinally for 4 years and the data were analyzed from 2016 to 2019. Based on preregistered hypotheses and an analytic plan, we examined whether specific brain connectivity patterns would be associated with longitudinal changes in scores on the Child Behavior Checklist (CBCL), a parental-report assessment used to screen for emotional, behavioral, and social problems and to predict psychiatric illnesses. Main Outcomes and Measures: We used the strength of resting-state fMRI connectivity at age 7 years to predict subsequent changes in CBCL measures 4 years later and investigated the mechanisms of change by associating brain connectivity changes with changes in the CBCL. Results: We analyzed data from a longitudinal brain development study involving children assessed at age 7 years (n = 94; 41 girls [43.6%]) and 11 years (n = 54; 32 girls [59.3%]). As predicted, less positive coupling at age 7 years between the medial prefrontal cortex and dorsolateral prefrontal cortex (DLPFC) was associated with a decrease in attentional symptoms by age 11 years (t49 = 2.38; P = .01; ß = 0.32). By contrast, a less positive coupling between a region implicated in mood, the subgenual anterior cingulate cortex (sgACC), and DLPFC at age 7 years was associated with an increase in internalizing (eg, anxiety/depression) behaviors by age 11 years (t49 = -2.4; P = .01; ß = -0.30). Logistic regression analyses revealed that sgACC-DLPFC connectivity was a more accurate predictor than baseline CBCL measures for progression to a subclinical score on internalization (t50 = -2.61; P = .01; ß = -0.29). We then replicated and extended the sgACC-DLPFC result in an independent sample of children with (n = 25) or without (n = 18) familial risk for MDD. Conclusions and Relevance: These resting-state fMRI metrics are promising biomarkers for the early identification of children at risk of developing MDD or attention-deficit/hyperactivity disorder.

Intrinsic Functional Brain Connectivity Predicts Onset of Major Depression Disorder in Adolescence: A Pilot Study.

Children with familial risk for major depressive disorder (MDD) have elevated risk for developing depression as adolescents. Here, we investigated longitudinally whether resting-state functional connectivity (RSFC) could predict the onset of MDD. In this pilot study, we followed a group of never-depressed children with familial risk for MDD and a group of age-matched controls without familial risk who had undergone an MRI study at 8-14 years of age. Participants were reassessed 3-4 years later with diagnostic interviews. We first investigated group differences in RSFC from regions in the emotion regulation, cognitive control, and default mode networks in the children who later developed MDD (converted), the children who did not develop MDD (nonconverted), and the control group. We then built a prediction model based on baseline RSFC that was independent of the group differences to classify the individuals who later developed MDD. Compared with the nonconverted group, the converted group exhibited hypoconnectivity between subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices. The nonconverted group exhibited higher sgACC-IPL connectivity than did both the converted and control groups, suggesting a possible resilience factor to MDD. Classification between converted and nonconverted individuals based on baseline RSFC yielded high predictive accuracy with high sensitivity and specificity that was superior to classification based on baseline clinical rating scales. Intrinsic brain connectivity measured in healthy children with familial risk for depression has the potential to predict MDD onset, and it can be a useful neuromarker in early identification of children for preventive treatment.

Neural markers of depression risk predict the onset of depression.

Although research highlights neural correlates of Major Depressive Disorder (MDD), it is unclear whether these correlates reflect the state of depression or a pre-existing risk factor. The current study examined whether baseline differences in brain activations, resting-state connectivity, and brain structural differences between non-symptomatic children at high- and low-risk for MDD based on familial depression prospectively predict the onset of a depressive episode or increases in depressive symptomatology. We re-assessed 44 participants (28 high-risk; 16 low-risk) who had undergone neuroimaging in a previous study 3-4 years earlier (Mean age at follow-up = 14.3 years, SD = 1.9 years; 45% females; 70% Caucasian). We investigated whether baseline brain imaging data (including an emotional face match task fMRI, resting-state fMRI and structural MRI) that differentiated the risk groups also predicted the onset of depression. Resting-state functional connectivity abnormalities in the default mode and cognitive control network that differentiated high-risk from low-risk youth at baseline predicted the onset of MDD during adolescence, after taking risk status into account. Increased functional activation to both happy and fearful faces was associated with greater decreases in self-reported depression symptoms at follow-up. This preliminary evidence could be used to identify youth at-risk for depression and inform early intervention strategies.

Very early family-based intervention for anxiety: two case studies with toddlers.

Anxiety disorders represent the most common category of psychiatric disorder in children and adolescents and contribute to distress, impairment and dysfunction. Anxiety disorders or their temperamental precursors are often evident in early childhood, and anxiety can impair functioning, even during preschool age and in toddlerhood. A growing number of investigators have shown that anxiety in preschoolers can be treated efficaciously using cognitive-behavioural therapy (CBT) administered either by training the parents to apply CBT strategies with their children or through direct intervention with parents and children. To date, most investigators have drawn the line at offering direct CBT to children under the age of 4. However, since toddlers can also present with impairing symptoms, and since behaviour strategies can be applied in older preschoolers with poor language ability successfully, it ought to be possible to apply CBT for anxiety to younger children as well. We therefore present two cases of very young children with impairing anxiety (ages 26 and 35 months) and illustrate the combination of parent-only and parent-child CBT sessions that comprised their treatment. The treatment was well tolerated by parents and children and showed promise for reducing anxiety symptoms and improving coping skills.

Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.

Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbic WM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturational WM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches.

Altered Intrinsic Functional Brain Architecture in Children at Familial Risk of Major Depression.

BACKGROUND: Neuroimaging studies of patients with major depression have revealed abnormal intrinsic functional connectivity measured during the resting state in multiple distributed networks. However, it is unclear whether these findings reflect the state of major depression or reflect trait neurobiological underpinnings of risk for major depression. METHODS: We compared resting-state functional connectivity, measured with functional magnetic resonance imaging, between unaffected children of parents who had documented histories of major depression (at-risk, n = 27; 8-14 years of age) and age-matched children of parents with no lifetime history of depression (control subjects, n = 16). RESULTS: At-risk children exhibited hyperconnectivity between the default mode network and subgenual anterior cingulate cortex/orbital frontal cortex, and the magnitude of connectivity positively correlated with individual symptom scores. At-risk children also exhibited 1) hypoconnectivity within the cognitive control network, which also lacked the typical anticorrelation with the default mode network; 2) hypoconnectivity between left dorsolateral prefrontal cortex and subgenual anterior cingulate cortex; and 3) hyperconnectivity between the right amygdala and right inferior frontal gyrus, a key region for top-down modulation of emotion. Classification between at-risk children and control subjects based on resting-state connectivity yielded high accuracy with high sensitivity and specificity that was superior to clinical rating scales. CONCLUSIONS: Children at familial risk for depression exhibited atypical functional connectivity in the default mode, cognitive control, and affective networks. Such task-independent functional brain measures of risk for depression in children could be used to promote early intervention to reduce the likelihood of developing depression.

Functional and structural brain correlates of risk for major depression in children with familial depression.

Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression.

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.

How Informative Is the CANTAB to Assess Executive Functioning in Children With ADHD? A Controlled Study.

OBJECTIVE: The authors examined the utility of the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) to evaluate executive functioning deficits in children with ADHD. METHOD: Participants were unmedicated children and adolescents with (n = 107) and without (n = 45) Diagnostic and Statistical Manual of Mental Disorders (4th ed.) ADHD. The authors administered the CANTAB Eclipse battery, which comprises specific tasks shown to be deficient in individuals with ADHD. RESULTS: With the exception of the affective go/no-go total omissions, ADHD participants were significantly more impaired on all other subtests of the CANTAB in comparison with controls. Effect sizes for individual CANTAB tests were largely in the medium range with the largest effect sizes seen in spatial working memory total and between errors. CONCLUSION: These CANTAB results are highly congruent with those reported in studies using traditional neuropsychological testing batteries, supporting the utility of the CANTAB to assess neuropsychological deficits in children with ADHD in clinical and research settings.

Efficacy of Interpretation Bias Modification in Depressed Adolescents and Young Adults.

This study evaluated the efficacy of a four-session Cognitive Bias Modification-Interpretation program for 45 depressed adolescents and young adults (14-21 years old; 12 males, 33 females; Beck Depressive Inventory, Second Edition ≥ 14) randomized to an active intervention condition (repeated exposure to positive outcomes of depression-relevant ambiguous scenarios; n=23) or a control condition (n=22). Both conditions experienced reductions on a Test of Interpretation Bias at post-treatment, with no significant between-group differences. When limited to those with negative bias at baseline, the intervention group showed greater improvement in interpretation bias at mid- and post-treatment. In addition, the intervention group overall had greater improvements in self-reported negative cognitions than the control group at post-intervention and two-week follow-up. However, there were no differences between groups in depression or anxiety symptom change. Potential factors contributing to mixed findings are discussed.

Early risk factors for psychopathology in offspring of parents with bipolar disorder: the role of obstetric complications and maternal comorbid anxiety.

OBJECTIVE: Offspring of parents with bipolar disorder (BD) are at increased risk for developing a range of psychiatric disorders. Although genetic factors clearly confer risk to offspring, environmental factors also play a role in increasing vulnerability. Such environmental factors may occur at the initial stages of development in the form of obstetric complications (OCs). The current investigation examined the relationship between OCs and the development of psychopathology in offspring at risk for BD and the influence of parental psychopathology in this relationship. METHODS: This cross-sectional study included 206 offspring of 119 parents with BD. Probit regression analyses examined associations between: (1) OC history and offspring psychopathology; and (2) maternal lifetime comorbid anxiety diagnoses and OCs in pregnancy/delivery with their offspring. Path analyses then tested whether OCs mediate the relationship between maternal comorbid anxiety disorders and offspring lifetime psychopathology. RESULTS: Results indicated a specific association between OCs, particularly delivery complications, and increased risk for offspring anxiety disorders. Data also showed a significant relationship between maternal anxiety disorder comorbidity and OCs. Finally, path analyses suggested that delivery complications act as a mediator in the relationship between comorbid maternal anxiety disorder and offspring anxiety disorder. CONCLUSIONS: Our findings lend support to the importance of identifying and reducing anxiety in pregnant woman with BD. The identification of OCs as early vulnerability factors for psychopathology in offspring at familial risk may also lead to earlier detection and intervention in these offspring.