M. H. J. Hillegers

High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls

BACKGROUND Schizophrenia is associated with lower intelligence and poor educational performance relative to the general population. This is, to a lesser degree, also found in first-degree relatives of schizophrenia patients. It is unclear whether bipolar disorder I (BD-I) patients and their relatives have similar lower intellectual and educational performance as that observed in schizophrenia. METHOD This cross-sectional study investigated intelligence and educational performance in two outpatient samples [494 BD-I patients, 952 schizophrenia spectrum (SCZ) patients], 2231 relatives of BD-I and SCZ patients, 1104 healthy controls and 100 control siblings. Mixed-effects and regression models were used to compare groups on intelligence and educational performance. RESULTS BD-I patients were more likely to have completed the highest level of education (odds ratio 1.88, 95% confidence interval 1.66-2.70) despite having a lower IQ compared to controls (β = -9.09, S.E. = 1.27, p < 0.001). In contrast, SCZ patients showed both a lower IQ (β = -15.31, S.E. = 0.86, p < 0.001) and lower educational levels compared to controls. Siblings of both patient groups had significantly lower IQ than control siblings, but did not differ on educational performance. IQ scores did not differ between BD-I parents and SCZ parents, but BD-I parents had completed higher educational levels. CONCLUSIONS Although BD-I patients had a lower IQ than controls, they were more likely to have completed the highest level of education. This contrasts with SCZ patients, who showed both intellectual and educational deficits compared to healthy controls. Since relatives of BD-I patients did not demonstrate superior educational performance, our data suggest that high educational performance may be a distinctive feature of bipolar disorder patients.

Perceived parental rearing of bipolar offspring

Objective:  To explore the impact of growing up with a parent with a bipolar disorder. First, we compared parental rearing behavior perceived by young adult offspring of bipolar parents with parental rearing behavior perceived by same aged young adults from the general population. Secondly, we examined the associations between perceived parental rearing behavior and parental psychopathology and psychopathology in offspring.

The role of life events and psychological factors in the onset of first and recurrent mood episodes in bipolar offspring: results from the Dutch Bipolar Offspring Study.

BACKGROUND Life events are an established risk factor for the onset and recurrence of unipolar and bipolar mood episodes, especially in the presence of genetic vulnerability. The dynamic interplay between life events and psychological context, however, is less studied. In this study, we investigated the impact of life events on the onset and recurrence of mood episodes in bipolar offspring, as well as the effects of temperament, coping and parenting style on this association. METHOD Bipolar offspring (n = 108) were followed longitudinally from adolescence to adulthood. Mood disorders were assessed with: the Kiddie Schedule of Affective Disorders and Schizophrenia - Present and Lifetime Version or the Structured Clinical Interview for DSM-IV Axis I disorders; life events with the Life Events and Difficulties Schedule; and psychological measures using the Utrecht Coping List, Temperament and Character Inventory and short-EMBU (memories of upbringing instrument). Anderson-Gill models (an extension of the Cox proportional hazard model) were utilized. RESULTS Life events were associated with an increased risk for first and, although less pronounced, subsequent mood episodes. There was a large confounding effect for the number of previous mood episodes; findings suggest a possible kindling effect. Passive coping style increased the risk of mood episode onset and recurrent episodes, but also altered the effect of life events on mood disorders. Harm avoidance temperament was associated with mood episode recurrence. CONCLUSIONS Life events are especially a risk factor in the onset of mood disorders, though less so in recurrent episodes. Psychological features (passive coping and harm-avoidant temperament) contribute to the risk of an episode occurring, and also have a moderating effect on the association between life events and mood episodes. These findings create potential early intervention strategies for bipolar offspring.

Immunological aspects of bipolar disorder.

ABSTRACT Introduction: Significant changes in immune function have been found in mood disorders. Controlled studies in bipolar disorder concerning cell-mediated immunity and thyroid autoimmunity are reviewed, and presented together with preliminary findings from our own ongoing study. Method: Using Medline and other sources, 14 controlled studies as well as some other relevant studies were found. Results: Bipolar disorder is associated with an acute phase response and activation of the cell-mediated immune system, and with an increased prevalence of antithyroid autoantibodies. Conclusion: Changes in immune function, in connection with neuroendocrine changes, may provide new hypotheses for the pathophysiology of mood disorders.

A dynamic course of T cell defects in individuals at risk for mood disorders.

OBJECTIVES T cell abnormalities have been repeatedly reported in adult patients with mood disorders, suggesting a role of these cells in the pathogenesis of these disorders. In the present study, we explored the dynamics of circulating T cell subsets over time in a population at high familial risk for developing a mood disorder. METHODS Children of a parent with bipolar disorder (bipolar offspring, N=140) were assessed at three time-points: adolescence, young adulthood and adulthood. We carried out a detailed fluorescence-activated cell sorting (FACS) analysis to determine various T cell subsets from frozen stored peripheral blood mononuclear cells of bipolar offspring and age- and gender-matched healthy controls at each time-point. RESULTS Throughout the period of observation reduced levels of CD3+ and CD3+ CD4+ T cells were observed. In bipolar offspring Th1, Th2, Th17 and natural T regulatory cells (Tregs) followed a dynamic course over time with reduced levels of Tregs in adolescence and a reduced relative number of Th1, Th17 cells in young adulthood. In post hoc analysis Tregs were inversely associated with the pro-inflammatory monocyte state determined previously (rs=-0.220, p=0.001). Significant associations between T cell subset abnormalities and psychopathology such as mood disorders were not found. CONCLUSIONS A subtle partial T cell defect was present in bipolar offspring from adolescence through adulthood. Within this defect the dynamic change of inflammatory and regulatory T cell subsets suggests a high inflammatory state during adolescence, a reduced inflammatory state during young adulthood and a virtually normalized state at adulthood.

Bipolar disorder in children and adolecents: a clinical reality?

Abstract The appearance, the differential diagnosis and the prevalence of bipolar disorder in children and adolescents is discussed. Among adolescents bipolar disorder appears to have a similar prevalence in the US and The Netherlands. However, among children it is frequently diagnosed in the US and hardly in The Netherlands. It is concluded that bipolar disorder tends to start earlier in the US than in the Netherlands. It is hypothesized that this may be related to a higher use of stimulants and antidepressants by US children diagnosed as ADHD or depression, respectively.

Baseline dimensional psychopathology and future mood disorder onset: findings from the Dutch Bipolar Offspring Study

To identify the early signs of mood disorder development, specifically bipolar disorder (BD), in a population at familial risk for BD.

Prediction of change in level of problem behavior among children of bipolar parents

Objective:  To determine the effects of familial loading, birth weight, and family problems on change in parent‐reported problems across a 14‐month period among children of bipolar parents.

A study of genetic and environmental contributions to structural brain changes over time in twins concordant and discordant for bipolar disorder

This is the first longitudinal twin study examining genetic and environmental contributions to the association between liability to bipolar disorder (BD) and changes over time in global brain volumes, and global and regional measures of cortical surface area, cortical thickness and cortical volume. A total of 50 twins from pairs discordant or concordant for BD (monozygotic: 8 discordant and 3 concordant pairs, and 1 patient and 3 co-twins from incomplete pairs; dizygotic: 6 discordant and 2 concordant pairs, and 1 patient and 7 co-twins from incomplete pairs) underwent magnetic resonance imaging twice. In addition, 57 twins from healthy twin pairs (15 monozygotic and 10 dizygotic pairs, and 4 monozygotic and 3 dizygotic subjects from incomplete pairs) were also scanned twice. Mean follow-up duration for all twins was 7.5 years (standard deviation: 1.5 years). Data were analyzed using structural equation modeling software OpenMx. The liability to BD was not associated with global or regional structural brain changes over time. Although we observed a subtle increase in cerebral white matter in BD patients, this effect disappeared after correction for multiple comparisons. Heritability of brain changes over time was generally low to moderate. Structural brain changes appear to follow similar trajectories in BD patients and healthy controls. Existing brain abnormalities in BD do not appear to progressively change over time, but this requires additional confirmation. Further study with large cohorts is recommended to assess genetic and environmental influences on structural brain abnormalities in BD, while taking into account the influence of lithium on the brain.

Validation of the Seven Up Seven Down Inventory in bipolar offspring: screening and prediction of mood disorders. Findings from the Dutch Bipolar Offspring Study

OBJECTIVE To validate the Seven Up Seven Down (7U7D), an abbreviated version of the General Behavior Inventory (GBI), as screener for mood disorders and test its ability to predict mood disorders over time in individuals at risk for bipolar disorder (BD). METHODS Bipolar offspring (n=108) were followed from adolescence into adulthood and assessed at baseline, 1-, 5- and 12 years follow-up (T1-T4 respectively). Offspring were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children--Present and Lifetime Version, Structured Clinical Interview for DSM-IV Axis I Disorders and the GBI. RESULTS Performance of the GBI and 7U7D was functionally similar for the depression (7D) scale, but variable for the mania (7U) scale. As screener for mood disorders (T4), the 7D showed fair diagnostic efficiency (area under the curve (AUC) 0.68, p<0.01, OR 1.53, 95% CI 1.15-2.03). The discriminative validity for BD and unipolar disorder was only close to significant (7D AUC 0.66, p=0.078; 7U AUC 0.67, p=0.067). In terms of prediction of mood disorder onset between T1 and T4, the 7D, but not the 7U, was associated with new onset (AUC 0.67, p<0.05; HR 1.14, 95% CI 1.07-1.23). The 7U7D did not achieve significant prediction of BD. LIMITATIONS Relative small sample size and limited generalizability. CONCLUSIONS Based on the current study, the 7U7D shows limited potential as screening instrument for mood disorders in bipolar offspring. The clinical utility of the 7U7D needs further exploration for use in clinical and research settings.