Mary Beth Hickey

Psychosocial functioning in offspring of parents with bipolar disorder

BACKGROUND Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. METHODS We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Childrens Global Assessment Scale (CGAS). RESULTS Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the childs Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. LIMITATIONS Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. CONCLUSIONS Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the childs own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the childs psychopathology may help reduce the risk for long-term functional impairment in offspring.

Dimensional psychopathology in offspring of parents with bipolar disorder.

Diler RS, Birmaher B, Axelson D, Obreja M, Monk K, Hickey MB, Goldstein B, Goldstein T, Sakolsky D, Iyengar S, Brent D, Kupfer D. Dimensional psychopathology in offspring of parents with bipolar disorder. Bipolar Disord 2011: 13: 670–678.

Mood lability among offspring of parents with bipolar disorder and community controls

Early identification of bipolar disorder (BP) symptomatology is crucial for improving the prognosis of this illness. Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study.

Altered amygdala-prefrontal response to facial emotion in offspring of parents with bipolar disorder

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls.

Differences in sleep disturbances among offspring of parents with and without bipolar disorder: association with conversion to bipolar disorder

Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diagnosed with BP at intake (BP/OB; n = 47), offspring of parents with BP without BP at intake (non‐BP/OB; n = 386), and offspring of matched control parents who did not have BP (controls; n = 301). We also examined the association of baseline sleep parameters with subsequent development of BP among the non‐BP/OB group.

Assessment of a Person-Level Risk Calculator to Predict New-Onset Bipolar Spectrum Disorder in Youth at Familial Risk

Importance Early identification of individuals at high risk for the onset of bipolar spectrum disorder (BPSD) is key from both a clinical and research perspective. While previous work has identified the presence of a bipolar prodrome, the predictive implications for the individual have not been assessed, to date. Objective To build a risk calculator to predict the 5-year onset of BPSD in youth at familial risk for BPSD. Design, Setting, and Participants The Pittsburgh Bipolar Offspring Study is an ongoing community-based longitudinal cohort investigation of offspring of parents with bipolar I or II (and community controls), recruited between November 2001 and July 2007, with a median follow-up period of more than 9 years. Recruitment has ended, but follow-up is ongoing. The present analysis included offspring of parents with bipolar I or II (aged 6-17 years) who had not yet developed BPSD at baseline. Main Outcomes and Measures This study tested the degree to which a time-to-event model, including measures of mood and anxiety, general psychosocial functioning, age at mood disorder onset in the bipolar parent, and age at each visit, predicted new-onset BPSD. To fully use longitudinal data, the study assessed each visit separately, clustering within individuals. Discrimination was measured using the time-dependent area under the curve (AUC), predicting 5-year risk; internal validation was performed using 1000 bootstrapped resamples. Calibration was assessed by comparing observed vs predicted probability of new-onset BPSD. Results There were 412 at-risk offspring (202 [49.0%] female), with a mean (SD) visit age of 12.0 (3.5) years and a mean (SD) age at new-onset BPSD of 14.2 (4.5) years. Among them, 54 (13.1%) developed BPSD during follow-up (18 with BD I or II); these participants contributed a total of 1058 visits, 67 (6.3%) of which preceded new-onset BPSD within the next 5 years. Using internal validation to account for overfitting, the model provided good discrimination between converting vs nonconverting visits (AUC, 0.76; bootstrapped 95% CI, 0.71-0.82). Important univariate predictors of outcome (AUC range, 0.66-0.70) were dimensional measures of mania, depression, anxiety, and mood lability; psychosocial functioning; and parental age at mood disorder. Conclusions and Relevance This risk calculator provides a practical tool for assessing the probability that a youth at familial risk for BPSD will develop new-onset BPSD within the next 5 years. Such a tool may be used by clinicians to inform frequency of monitoring and treatment options and for research studies to better identify potential participants at ultra high risk of conversion.

Prospective longitudinal course of aggression among adults with bipolar disorder

Bipolar disorder (BP) has been associated with increased aggressive behaviors. However, all existing studies are cross‐sectional and include forensic or inpatient populations and many do not take into account the effects of comorbid conditions. The goal of this study was to evaluate the longitudinal course of aggression among adult outpatients with BP compared with non‐BP patients and healthy controls.

Categorical and dimensional psychopathology in Dutch and US offspring of parents with bipolar disorder: A preliminary cross-national comparison

OBJECTIVE Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands. METHODS We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL). RESULTS Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports. LIMITATIONS Preliminary measure of inter-site reliability. CONCLUSIONS We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study.

Risk for Suicidal Ideation Among the Offspring of Bipolar Parents: Results From the Bipolar Offspring Study (BIOS)

The objective of the study was to examine rates and identify risk factors for suicidal ideation among offspring of parents with bipolar disorder. Subjects included 388 offspring of parents with bipolar disorder and 250 offspring of matched community controls enrolled in the Pittsburgh Bipolar Offspring Study (BIOS). Offspring of bipolar probands displayed greater rates of lifetime suicidal ideation than offspring of controls (33% versus 20%). Factors most strongly associated with lifetime suicidal ideation in offspring of bipolar parents included offspring mood disorder, hostility, recent sexual abuse, and family conflict. Offspring of parents with bipolar disorder are at elevated risk for suicidal ideation as compared with offspring of controls. Suicide risk assessment in this population should attend to specific risk factors identified.

Preliminary investigation of the relationships between sleep duration, reward circuitry function, and mood dysregulation in youth offspring of parents with bipolar disorder

BACKGROUND Altered reward circuitry function is observed in individuals with bipolar disorder (BD) and their unaffected offspring (OBP). While OBP are at elevated risk for BD, modifiable risk factors that may exacerbate neural vulnerabilities in OBP remain under-characterized. As sleep loss is strongly linked to mania in BD, this study tested associations between sleep duration, reward circuitry function, and mood dysregulation in OBP. METHODS Two groups of youth unaffected with BD (9-17yr) completed a number-guessing fMRI reward paradigm: 25 OBP and 21 age-sex-IQ-matched offspring of control parents with non-BD psychopathology (OCP), to differentiate risk for BD from risk for psychopathology more broadly. Regressions tested effects of group status, self-reported past-week sleep duration, and their interaction on neural activity and bilateral ventral striatum (VS) functional connectivity to win>control. Correlations with parent-reported mood dysregulation were assessed. RESULTS Group effects were observed for right posterior insula activity (OCP>OBP) and VS-left posterior insula connectivity (OBP>OCP). Group⁎sleep duration interactions were observed for left dorsal anterior-mid-cingulate (daMCC) activity and VS-left anterior insula/ventrolateral prefrontal cortex (VLPFC) connectivity. Specifically, sleep duration and daMCC activity were positively related in OBP, but negatively related in OCP and sleep duration and VS-left anterior insula/VLPFC connectivity were negatively related in OBP, but positively in OCP. Additionally, increased VS-left posterior insula connectivity and VS-left anterior insula/VLPFC connectivity were associated with greater mood dysregulation in OBP only. LIMITATIONS Cross-sectional design and small sample size. CONCLUSIONS Altered reward-related VS-insula connectivity could represent a neural pathway underpinning mood dysregulation in OBP, and may be modulated by shortened sleep duration.