Donna S. Ronsaville

A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder

Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction.

Suicidal ideation and attempts: a longitudinal investigation of children of depressed and well mothers

OBJECTIVE This study uses a prospective longitudinal design to examine suicidality (ideation, plans, attempts, and completions) in children and adolescents, to compare suicidality in the offspring of depressed and well mothers, and to identify correlates and predictors of suicidality. METHOD Two children (n = 192) from each of the families in an ongoing longitudinal study of the offspring of mothers with major depressive disorder (n = 42), with bipolar disorder (n = 26), or without past or current psychiatric diagnosis (n = 30) were studied. Assessment of suicidality, based on diagnostic interviews, was made when the younger of the sibling pairs were approximately 6, 9, and 14 years of age and older siblings were approximately 6, 9, 13, and 18 years of age. RESULTS Children of depressed mothers were more likely to report suicidal thoughts or behaviors than were children of well mothers (particularly the older sibling cohort). Developmental trajectories of suicidality differed for offspring of mothers with major depressive disorder and bipolar disorder. Links were found between lifetime reports of suicidality and the adolescents mood problems (e.g., hypomanic behavior), coping strategies, and parental rejection. Also, childs and mothers suicidality were related. CONCLUSIONS These findings have implications for planning interventions targeted at preventing suicide in youth.

Long-term outcomes of youth who manifested the CBCL-Pediatric Bipolar Disorder phenotype during childhood and/or adolescence.

OBJECTIVE Recent studies have identified a Child Behavior Checklist (CBCL) profile that characterizes children with severe aggression, inattention, and mood instability. This profile has been coined the CBCL-Pediatric Bipolar Disorder (PBD) phenotype, because it is commonly seen among children with bipolar disorder. However, mounting evidence suggests that the CBCL-PBD may be a better tool for identifying children with severe functional impairment and broad-ranging psychiatric comorbidities rather than bipolar disorder itself. No studies have followed individuals with the CBCL-PBD profile through adulthood, so its long-term implications remain unclear. The present authors examined diagnostic and functional trajectories of individuals with the CBCL-PBD profile from early childhood through young adulthood using data from a longitudinal high-risk study. METHOD Participants (n=101) are part of a 23-year study of youth at risk for major mood disorder who have completed diagnostic and functional assessments at regular intervals. RESULTS Across development, participants with the CBCL-PBD phenotype exhibited marked psychosocial impairment, increased rates of suicidal thoughts and behaviors and heightened risk for comorbid anxiety, bipolar disorder, cluster B personality disorders and ADHD in young adulthood, compared to participants without this presentation. However, diagnostic accuracy for any one particular disorder was found to be low. CONCLUSIONS Children with the CBCL-PBD profile are at risk for ongoing, severe, psychiatric symptomatology including behavior and emotional comorbidities in general, and bipolar disorder, anxiety, ADHD, cluster B personality disorders in particular. However, the value of this profile may be in predicting ongoing comorbidity and impairment, rather than any one specific DSM-IV diagnosis.

Neuropsychological Functioning in Adolescent Children of Mothers with a History of Bipolar or Major Depressive Disorders

BACKGROUND Growing evidence demonstrates an association of neuropsychological deficits with mood disorders, but it is not yet clear whether these deficits are risk factors or are concomitant with the symptoms. This study examines the neuropsychological functioning of a group of adolescent offspring who are at risk for a mood disorder by virtue of being raised by mothers who have been diagnosed with major depressive disorder (MDD) or bipolar disorder (BPD). METHODS Adolescent offspring of mothers with BPD (n = 43) or MDD (n = 72) and of psychiatrically well parents (n = 50) completed a battery of neuropsychological tests to assess executive functioning, memory, and attention. RESULTS Children of mothers with BPD showed deficits in executive functioning and selective deficits in spatial memory and attention, in comparison with children of well mothers. Deficits were not found for children of MDD mothers. CONCLUSIONS Knowledge of these neurocognitive processes could aid ultimately in determining whether neurocognitive deficits precede BPD, whether unique profiles are associated with various types of mood disorders, and who may benefit from interventions.

Clinical Subtypes of Depression Are Associated with Specific Metabolic Parameters and Circadian Endocrine Profiles in Women: The Power Study

Background Major depressive disorder (MDD) has been associated with adverse medical consequences, including cardiovascular disease and osteoporosis. Patients with MDD may be classified as having melancholic, atypical, or undifferentiated features. The goal of the present study was to assess whether these clinical subtypes of depression have different endocrine and metabolic features and consequently, varying medical outcomes. Methods Premenopausal women, ages 21 to 45 years, with MDD (N = 89) and healthy controls (N = 44) were recruited for a prospective study of bone turnover. Women with MDD were classified as having melancholic (N = 51), atypical (N = 16), or undifferentiated (N = 22) features. Outcome measures included: metabolic parameters, body composition, bone mineral density (BMD), and 24 hourly sampling of plasma adrenocorticotropin (ACTH), cortisol, and leptin. Results Compared with control subjects, women with undifferentiated and atypical features of MDD exhibited greater BMI, waist/hip ratio, and whole body and abdominal fat mass. Women with undifferentiated MDD characteristics also had higher lipid and fasting glucose levels in addition to a greater prevalence of low BMD at the femoral neck compared to controls. Elevated ACTH levels were demonstrated in women with atypical features of depression, whereas higher mean 24-hour leptin levels were observed in the melancholic subgroup. Conclusions Pre-menopausal women with various features of MDD exhibit metabolic, endocrine, and BMD features that may be associated with different health consequences. Trial Registration ClinicalTrials.gov NCT00006180

Maternal and environmental factors influence the hypothalamic-pituitary-adrenal axis response to corticotropin-releasing hormone infusion in offspring of mothers with or without mood disorders.

Individuals with melancholic major depression exhibit basal hypercortisolism and an attenuated ACTH response to exogenous corticotropin-releasing hormone (CRH) infusion. Given the greater incidence of depression in children of depressed parents, we examined the ACTH and cortisol responses to ovine CRH (oCRH) infusion in 63 adolescent offspring of mothers with major depression, bipolar illness, or no psychiatric illness. Psychiatric and observational assessments of these families had been conducted over the course of 10 years preceding this study. We examined the childrens responses to CRH in relation to maternal characteristics and family environment and found the following: (a) cortisol responses were negatively related to chronic family stress and (b) offspring of depressed mothers with an avoidant personality disorder showed an exaggerated ACTH response. In addition, adolescents in late puberty (Tanner 4 and 5) had lower ACTH and cortisol responses to oCRH infusion than those in early puberty. Further, offspring with early histories of mood problems, and those who developed major depressive disorder as young adults, did not exhibit basal hypercortisolism but did show an attenuated ACTH response to CRH. Our results add to the growing body of literature showing the influence of maternal characteristics and environmental factors on hypothalamic-pituitary-adrenal axis patterns in children.

Quality of life and pain in premenopausal women with major depressive disorder: The POWER Study

BackgroundWhereas it is established that organic pain may induce depression, it is unclear whether pain is more common in healthy subjects with depression. We assessed the prevalence of pain in premenopausal women with major depression (MDD). Subjects were 21- to 45-year-old premenopausal women with MDD (N = 70; age: 35.4 +/- 6.6; mean +/- SD) and healthy matched controls (N = 36; age 35.4 +/- 6.4) participating in a study of bone turnover, the P.O.W.E.R. (P remenopausal, O steopenia/Osteoporosis, W omen, Ale ndronate, Depr ession) Study.MethodsPatients received a clinical assessment by a pain specialist, which included the administration of two standardized forms for pain, the Brief Pain Inventory – Short Form, and the Initial Pain Assessment Tool, and two scales of everyday stressors, the Hassles and Uplifts Scales. In addition, a quality-of-life instrument, the SF-36, was used. The diagnosis of MDD was established by a semi-structured interview, according to the DSM-IV criteria. Substance P (SP) and calcitonin-gene-related-peptide (CGRP), neuropeptides which are known mediators of pain, were measured every hour for 24 h in a subgroup of patients (N = 17) and controls (N = 14).ResultsApproximately one-half of the women with depression reported pain of mild intensity. Pain intensity was significantly correlated with the severity of depression (r2 = 0.076; P = 0.04) and tended to be correlated with the severity of anxiety, (r2 = 0.065; P = 0.07), and the number of depressive episodes (r2 = 0.072; P = 0.09). Women with MDD complained of fatigue, insomnia, and memory problems and experienced everyday negative stressors more frequently than controls. Quality of life was decreased in women with depression, as indicated by lower scores in the emotional and social well-being domains of the SF-36. SP (P < 0.0003) and CGRP (P < 0.0001) were higher in depressed subjects.ConclusionWomen with depression experienced pain more frequently than controls, had a lower quality of life, and complained more of daily stressors. Assessment of pain may be important in the clinical evaluation of women with MDD. SP and CGRP may be useful biological markers in women with MDD.

A prospective high-risk study of the association among maternal negativity, apparent frontal lobe dysfunction, and the development of bipolar disorder

In a previous paper, the authors found that impairment on the Wisconsin Card Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young adulthood among offspring of mothers with bipolar illness. In the present study, the authors explore the contribution of maternal characteristics, beyond maternal mood disorder, to the prediction of offspring dysfunction on the WCST. Results showed that maternal bipolar disorder and maternal negativity were both predictive of impaired performance on the WCST during adolescence. The contribution of maternal negativity to offspring WCST impairment was not better explained by maternal personality disorder, mothers functional impairment, family loading for bipolar disorder, or offspring disruptive behavioral disturbance. Findings did not support a moderator model. However, support was found for a mediation model in which maternal negativity contributed to risk for offspring bipolar disorder through its negative association with apparent frontal lobe functioning, as measured by the WCST. Findings are discussed from the perspective of a vulnerability-stress model. In addition, the authors consider the possibility that maternal negativity and offspring impairment on the WCST may be reflective of a common heritable trait.

Continuity and cascade in offspring of bipolar parents: a longitudinal study of externalizing, internalizing, and thought problems.

There is growing evidence that many offspring of bipolar parents will develop moderate to severe forms of psychopathology during childhood and adolescence. The purpose of this study was to apply growth curve models to evaluate developmental progression with regard to continuity and cascades representative within the context of a family risk study of bipolar disorder (BD). Repeated assessments of externalizing, internalizing, and thought problems, spanning more than a decade, were examined in a total of 94 offspring of parents with BD (O-BD), major depressive disorder (O-UNI), or no significant psychiatric or medical problems (O-WELL). Continuity was defined by the growth curve of the O-WELL group who exhibited low levels of problems from early childhood through late adolescence. Discontinuity, as evidenced by greater complexity of growth curves relative to the O-WELL group, was exhibited in the at- risk offspring groups for internalizing problems. Different patterns of developmental cascades were supported for the at-risk group with O-UNI showing a robust cascade from self-regulatory deficits (externalizing problems) to internalizing problems. There was also support for a cascade from self-regulatory deficits to thought problems across the entire group (with some support that this pattern was accounted for primarily by O-BD). This study not only serves to advance our understanding of the risks associated with a family history of BD, but also provides a novel approach to examining developmental cascades.