Diagnostic Precursors to Bipolar Disorder in Offspring of Parents With Bipolar Disorder: A Longitudinal Study

Abstract

Objective Identify diagnostic risk factors of mania/hypomania in the offspring of parents with bipolar disorder (“high-risk offspring”). Method High-risk offspring aged 6-18 years (n=391) and demographically-matched offspring (n=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean interval 2.5 years; mean duration 6.8 years). Results High-risk offspring, as compared to community offspring, had significantly higher rates of subthreshold (hypo)manic (13.3% vs. 1.2%, p<.0001), manic/hypomanic (9.2% vs. 0.8%, p=.0003) and major depressive episodes (32.0% vs. 14.9%, p<.0001). They also had higher rates of attention-deficit hyperactivity (30.7% vs. 18.2%, p=.01), disruptive behavior (27.4% vs. 15.3%, p=.03), anxiety (39.9% vs. 21.8%, p=.0002), and substance use disorders (20.0% vs. 10.1%, p=.008), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% vs. 13.7%; p=.10). Multivariate Cox regressions in the high-risk offspring showed that subthreshold (hypo)manic episodes (Hazard Ratio 2.29, p=.03), major depressive episodes (Hazard Ratio 1.99, p=.05), and disruptive behavior disorders (Hazard Ratio 2.12, p=.03) were associated with subsequent mania/hypomania. Only subthreshold (hypo)manic episodes (Hazard Ratio 7.57, p<.0001) were associated when analyses were restricted to prospective data. Conclusions Subthreshold (hypo)manic episodes were a diagnostic risk factor for the development of mania/hypomania in the offspring of parents with bipolar disorder, and should be a target for clinical assessment and future treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

Web‐based integrated bipolar parenting intervention for parents with bipolar disorder: a randomised controlled pilot trial

“…BD impacts negatively on, sleep/wake cycles, impulse control, communication and motivation, which may undermine adaptive parenting (Phelan, Lee, Howe, & Walter, 2006; Vance, Jones, Espie, Bentall, & Tai, 2008); whilst mood variation can trigger inconsistent parenting (David, Styron, & Davidson, 2011; Dolman, Jones, & Howard, 2013). Support for parents with BD is particularly important as their children are at high‐risk for psychiatric conditions, including attention deficit hyperactive disorder (ADHD), depression, anxiety, substance abuse, sleep disorders and BD (Axelson et al., 2015; Duffy, Jones, Goodday, & Bentall, 2016; Mesman, Nolen, Reichart, Wals, & Hillegers, 2013). Despite this, few of these children receive clinical support (Calam, Jones, Sanders, Dempsey, & Sadhnani, 2012; Jones, Tai, Evershed, Knowles, & Bentall, 2006) which risks more severe psychological disorders in later life (Duffy et al., 2016).…”

The predictive value of childhood subthreshold manic symptoms for adolescent and adult psychiatric outcomes

“…Evidence from prospective evaluations of offspring of at least one BD parent suggests that attenuated manic symptoms frequently predate syndromal onset (Axelson et al, 2015;Hafeman et al, 2016;Malhi et al, 2014). However, in general population cohorts the relationship between subthreshold symptoms and clinical outcomes has modest contemporaneous specificity and predictive value.…”

Children in the US are at High Risk for Psychiatric Disorders: Early Monitoring by Parents May Enhance Awareness and Treatment

“…The offspring of patients in the US had a psychiatric illness in 46.3% compared to those from Europe who had a 16.1% incidence of illness. These lower incidences than those seen by Axelson et al [1] were based on patient report and not prospective diagnostic interviews or long term follow up. The US offspring had significantly (p<0.001) more depression, bipolar disorder, and "other" illnesses compared to the Europeans [9].…”

“…In a recent study by Axelson et al [1] children of a parent with bipolar disorder or community controls without a bipolar diagnosis were followed prospectively for 7 years. A very high incidence of childhood psychiatric illness was observed in both groups.…”

“…The offspring of a parent with bipolar disorder had a major psychiatric diagnosis 74.2% of the time, while the offspring of the controls still had a disturbingly high incidence of illness of 48.4%. The lifetime diagnosis rates as listed in Table 2 in Axelson et al [1] (in the high risk children versus the controls) included: an anxiety disorder (39.9% vs 21.8%); major depressive (32.0% vs 14.9%); ADHD (30.7% vs 18.1%); disruptive behavioral disorder (27.4% vs 15.3%); substance use disorders (19.9% vs 10.1%); and full to sub threshold bipolar disorder (22.5% vs 2.0%).…”