Elsevier

Journal of Affective Disorders

Volume 238, 1 October 2018, Pages 244-249
Journal of Affective Disorders

Research paper
Does the course of manic symptoms in pediatric bipolar disorder impact the course of conduct disorder? Findings from four prospective datasets

https://doi.org/10.1016/j.jad.2018.05.020Get rights and content

Highlights

  • Conduct disorder and bipolar disorder are prevalent and highly morbid psychiatric conditions.

  • There is a high and bidirectional overlap between conduct disorder and bipolar disorder.

  • Youth with both disorders are at extremely high risk for very adverse outcomes, including psychiatric hospitalization, suicidal risk, and addictions.

  • While bipolar disorder can be treated pharmacologically, conduct disorder cannot. Using longitudinal, naturalistic data, this study tested the hypothesis that reduction of symptoms of mania will lead to reduction of symptoms of conduct disorder. The findings support this hypothesis.

Abstract

Background

To assess whether the course of pediatric bipolar-I (BP-I) disorder impacts the course of conduct disorder (CD)/antisocial personality disorder (ASPD). We hypothesized that remission of manic symptoms in BP-I youth will be associated with remission of CD/ASPD.

Methods

We used data from four longitudinal datasets of carefully characterized and comprehensively assessed youth with structured diagnostic interview based diagnoses of BP-I disorder and CD/ASPD assessed at baseline in childhood and at follow-up onto adolescent years. The baseline sample consisted of 240 subjects with full BP-I disorder. The average follow-up time was 6.6 ± 2.4 years.

Results

Subjects with remitting BP-I disorder in adolescent years had a significantly lower one-year prevalence of CD or ASPD compared to those with persistent BP-I disorder (χ2= 10.35, p = 0.001).

Limitations

Our inferences were derived from the examination of naturalistic longitudinal follow-up data and not results of a clinical trial.

Conclusions

Results indicate that remission of manic symptoms at the adolescent follow up in youth with BP-I disorder were associated with a significant decrease in rates of CD/ASPD. These results suggest that targeting manic symptoms in youth with BP-I disorder could mitigate the course of CD/ASPD in youth. Considering the high morbidity and disability associated CD/ASPD in youth and the limited treatment options available to address it, if replicated, these findings would have very important clinical and public health significance.

Introduction

A body of literature documents a high and bidirectional overlap between bipolar-I (BP-I) disorder and conduct disorder (CD)/antisocial personality disorder (ASPD) in both clinical (Biederman et al., 1996b, Faraone et al., 1998, Geller et al., 1994, Kovacs and Pollock, 1995, Kutcher et al., 1989, Wozniak et al., 1995a, Wozniak et al., 1995b) and epidemiological samples (Lewinsohn et al., 1995).

Our own studies documented a high and bidirectional comorbidity between BP-I disorder and CD within and without the context of ADHD (Biederman et al., 1999). Examination of symptoms of mania and patterns of familial aggregation in youth with BP-I disorder and CD indicated that the presence of one disorder did not alter the symptomatic picture or familiality of the other. In other words, the symptom profile of BP-I disorder and CD was the same irrespective of the comorbidity with the other disorder. Likewise, both BP-I disorder and CD bred true in families irrespective of the presence of the other disorder. We also found significant evidence of cosegregation between CD and BP-I disorder among relatives of probands with comorbid CD + BP-I disorder supporting the hypothesis the CD + BP-I disorder may represent a distinct subgroup of either BP-I disorder or CD (Wozniak et al., 2001). More recently, Masi et al. (2008) examined the co-occurrence of CD and BP-I disorder in a sample of 307 youth using structured clinical interviews and found that youth with comorbid CD plus BP-I disorder had higher rates of aggression when compared with those with CD alone and had the highest risk for substance abuse. Likewise, Olvera et al. (2014) reported that subjects with the co-occurrence of CD and BP-I disorder had poorer lifetime functioning, more mood and attentional dysfunction, and more medication exposure than subjects with CD who were not bipolar.

Furthermore, Mallett et al. (2009) using data from a random sample of youth before the juvenile courts in two Northeast Ohio counties in the USA (n = 555) over a 4‐year time frame, identified a lifetime diagnosis of depression and/or bipolar disorder to be predictive of later youth delinquency adjudication. Webb et al. (2014) compared risks for suicidality and criminality in a national cohort of people diagnosed with bipolar disorder using data from the Swedish national registers. Findings revealed that 22.2% of bipolar disorder cohort members engaged in suicidal or criminal acts after diagnosis. They were at greatly elevated risk for completed suicide (risk ratio = 18.8; 95% CI, 16.0–22.2), attempted suicide (risk ratio = 14.3; 95% CI, 13.5–15.2), violent crime (risk ratio = 5.0; 95% CI, 4.6–5.4), and nonviolent crime (risk ratio = 2.9; 95% CI, 2.8–3.1) compared with the general population.

Work by our group and others showed that both predatory and non-predatory types of aggression occur in youth with BP-I disorder (Biederman et al., 1999, Eichelman, 1987, Eichelman, 1992). Such aggressive behaviors can lead to arrest and incarceration. For example, Plizka et al. (2000) found that 20% of adolescents admitted to a juvenile detention center met criteria for mania and those with mania had much higher rates of substance use disorders than those with bipolar disorder. In our studies (Biederman et al., 1996a, Biederman et al., 1999), the rate of psychiatric hospitalization in children with CD in the absence of BP-I disorder was very low and indistinguishable from that of youth with ADHD. In contrast, it was very high in those with comorbid CD with BP-I disorder, suggesting that the presence of BP-I disorder drives the need for psychiatric hospitalization in children with CD.

While pharmacological treatments can successfully treat pediatric BP-I disorder (Liu et al., 2011), pharmacological approaches are less certain in the management of CD youth (Thomas, 2016). A series of small early controlled clinical trials (Campbell et al., 1995, Campbell et al., 1984, Cueva et al., 1996, Malone et al., 2000, Rifkin et al., 1997) in hospitalized aggressive children with CD suggested that mood stabilizers (lithium carbonate and carbamazepine) (Steiner et al., 2003) may be effective in the treatment of aggressive symptoms in CD children. Similar findings were reported in more recent small studies of risperidone in youths with conduct disorder and aggressivity (Findling et al., 2000) and in a sample of children with subnormal intelligence, aggression and disruptive behavior disorders (Aman et al., 2002), as well as a study of olanzapine in the treatment of adolescents with severe conduct disorder with marked aggressive symptoms (Masi et al., 2006).

While none of these studies addressed the question of whether these children may have had comorbidity with bipolar disorder, in all these studies, the investigators targeted aggression in the context of CD with antimanic agents. These findings suggest that the therapeutic benefits observed in aggressive children with CD with anti-manic treatments could have been due to their anti-manic effects of the medications used targeting manic symptoms. However, to the best of our knowledge, no study to date directly assessed whether treating manic symptoms in youth with BP-I disorder improves symptoms of CD.

In the absence of clinical trial data, one approach to indirectly probe this important issue is to examine whether the naturalistic longitudinal course of manic symptoms in BP-I youth impacts the course of CD overtime. Specifically, prospective data can provide important insight as to whether remission of manic symptoms in youth with BP-I disorder is associated with remission of CD symptoms. Since improvement of manic symptoms can be achieved in the short-term with appropriate antimanic armamentarium (Liu et al., 2011), this information would support the conduct of clinical trials targeting manic symptoms in youth with CD and comorbid BP-I disorder with antimanic agents.

Whether the course of manic symptoms in youth with BP-I disorder impacts the course of CD has important implications. Clinically, such information will encourage clinicians to consider the diagnosis of BP-I disorder in mood dysregulated youth with CD and address the BP-I disorder component of the clinical picture with appropriate antimanic treatment. Considering the morbidity and poor prognosis associated with CD, the ability to address manic symptoms in CD youth with comorbid BP-I disorder may allow these very high-risk youths to attain clinical stability and avoid institutionalization and incarceration, an issue of high societal and public health relevance.

The main aim of the present study was to assess whether the course of pediatric BP-I disorder impacts the course of CD/ASPD. To this end we used data from four longitudinal datasets of carefully characterized and comprehensively assessed youth with structured diagnostic interview based diagnoses of BP-I disorder and CD assessed at baseline in childhood and at follow-up during adolescent years. We hypothesized that remission of manic symptoms in BP-I youth will be associated with remission of CD.

Section snippets

Sample

The sample was derived from four independent studies using identical assessment methodology: Two were prospective controlled family studies of boys and girls 6 to 17 years of age with and without ADHD (Boys Study: N=140 ADHD and N = 120 Controls; Girls Study: N = 140 ADHD and N = 122 Controls) (Biederman et al., 1996a, Biederman et al., 2006); The third one was a prospective controlled family study of youth 10 to 18 years of age with (N = 105) and without (N = 98) DSM-IV pediatric BP-I disorder

Demographic characteristics of the sample

Our baseline sample consisted of 240 subjects with full BP-I disorder. There were no significant differences between the studies in the baseline rate of CD/ASPD (Boys ADHD: 53% vs. Girls ADHD: 33% vs. BP Family: 54% vs. BP Controlled: 55%; χ2= 2.60, p = 0.45). Subjects at baseline were an average age of 11.8 ± 3.5 years, had an average socioeconomic status (SES) of 1.9 ± 1.0, and were predominantly male (72%) and Caucasian (95%). At baseline, 44% of patients were both taking medication and

Discussion

Using data from four naturalistic longitudinal datasets of youth of both sexes with and without BP-I disorder and ADHD, we examined whether the course of pediatric BP-I disorder affects the course of CD/ASPD. Results indicate that remission of manic symptoms in youth with BP-I disorder was associated with a significant decrease in rates of CD/ASPD. If replicated, these results suggest that targeting symptoms of mania in youth with CD with comorbid BP-I disorder could indirectly mitigate the

Author Contributions

Dr. Biederman had full access to all the data in the study, conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript.

Ms. Fitzgerald was the statistician for this study, analyzed the data, and critically reviewed and revised the manuscript.

Ms. Woodworth carried out the literature search, assisted with interpretation of the data, assisted with drafting the manuscript, reviewed and revised the manuscript.

Dr. Yule assisted with interpretation of

Role of the funding source

This work was supported in part by National Institute of Health grants R01HD036317 (JB), R01MH050657 (JB), R01HD37999 (SF), R01HD37694 (SF), R01DA12945 (TW), K24DA016264 (TW), and R01MH66237-5 (JW), as well as by a grant from the Stanley Foundation (Dr. Biederman, PI), and the MGH Pediatric Psychopharmacology Council Fund. The research leading to these results has received funding from the European Union Seventh Framework Programme [FP7/2007–2013] under grant agreement n° 602805 (Faraone). The

Conflicts of interest

Dr. Joseph Biederman is currently receiving research support from the following sources: AACAP, The Department of Defense, Food & Drug Administration, Headspace, Lundbeck, Neurocentria Inc., NIDA, PamLab, Pfizer, Shire Pharmaceuticals Inc., Sunovion, and NIH. Dr. Biederman has a financial interest in Avekshan LLC, a company that develops treatments for attention deficit hyperactivity disorder (ADHD). His interests were reviewed and are managed by Massachusetts General Hospital and Partners

Acknowledgements

None.

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