Elsevier

Comprehensive Psychiatry

Volume 78, October 2017, Pages 130-139
Comprehensive Psychiatry

Substance use disorders in adolescent and young adult relatives of probands with bipolar disorder: What drives the increased risk?

https://doi.org/10.1016/j.comppsych.2017.07.010Get rights and content

Abstract

Background

Adults with bipolar disorder (BD) have higher rates of substance use disorders (SUDs) compared to the general population. SUD rates in young offspring/relatives of BD probands, as well as factors which drive those rates, are not as well-characterized.

Methods

We aimed to examine SUD prevalence among adolescent/young adult offspring and relatives of probands with and without BD. Data were collected from five sites in the US and Australia during 2006–2011. Youth offspring/relatives (“Relatives of BD probands;” n = 267; mean age = 16.8 years; ± 2.9 S.D.), identified through a proband family member with DSM-IV BD (Type I or II), were compared to offspring/relatives of control probands (“relatives of control probands;” n = 149; mean age = 17.4 years; ± 2.9 S.D.). Logistic regression with generalized estimating equations was used to compare the groups across a range of substance use and SUD variables. Odds ratios were calculated for lifetime prevalence of substance outcomes.

Results

Bivariate analyses showed DSM-IV SUDs were more prevalent among relatives of BD probands than among relatives of control probands (29% vs. 18%; p = 0.01). Generalized estimating equation models showed BD mood and childhood-onset externalizing disorders in adolescent and young adult relatives to each significantly increase the odds (OR = 2.80–3.17; p < 0.02) for the development of several substance variables among all relatives, whereas the risk of SUDs in relatives was not increased when the relatives had no mood or externalizing disorders themselves.

Conclusion

Relatives of BD probands with lifetime mood and externalizing disorders report more substance use/SUDs than relatives of control probands. In contrast, SUD outcomes in relatives of BD probands without mood or externalizing disorders were no different from control relatives without psychopathology. Early recognition and treatment of psychiatric disorders may lead to less substance use in this highly vulnerable population.

Introduction

The association between substance use disorders (SUDs) and mood disorders, particularly bipolar disorder (BD), has been well documented [1], [2], [3], [4]. Estimates of lifetime comorbidity of BD and SUDs range from 16 to 54% [5], [6], with a recent meta-analysis finding a mean prevalence of 33% for comorbid BD and SUDs [7]. This comorbidity is particularly important from a prognostic standpoint, with multiple studies documenting significantly worse mental and physical health outcomes in individuals afflicted by both SUDs and BD [8], [9]. SUDs complicate treatment and course of BD, and vice versa. Co-occurring SUDs have been shown to be particularly associated with increased frequency and duration of mood episodes, increased preoccupation with suicide, decreased treatment compliance and more severe cognitive impairment in individuals with BD [3], [10]. Tobacco is the most commonly used drug of abuse among individuals with BD and is used 1.5–3 times more often than in the general population [11], [12], [13], [14]. Tobacco use is of particular interest given recent evidence of earlier death rates in both men and women with BD, driven partly by tobacco-related illnesses [15]. Alcohol, cannabis, and cocaine are the next most commonly misused substances among individuals with BD [3]. Explanatory models postulate that substance use is elevated among individuals with BD, compared to the general population, because of common risk factors. These common risk factors may increase expression of a range of self-regulatory deficits which may manifest in symptoms of mood disorders or SUDs [16].

Prominent models of addiction liability have largely focused on trajectories toward SUDs from childhood externalizing disorders [17], [18], [19], [20]. Pathways toward SUDs among youth with BD diagnoses are also becoming increasingly well characterized [21], [22], [23], [24]. In youth, the combination of conduct disorder and BD has been associated with especially high rates of SUDs in relatives [21], indicating an overlap between the risk factors for BD and SUDs. Genome-wide association analysis has provided evidence of a significant genetic overlap in the risk factors of BD and SUDs [25]. However, the relative influence of a family history of BD and other risk factors (e.g., adolescent psychopathology, parental SUDs, etc.) on SUD development in BD remain unclear, as does information pertaining to relative age of onset of each disorder category. Understanding mechanisms leading to an underlying SUD in BD are essential to the development of appropriate preventive and treatment interventions. For example, if parenting practices associated with having BD are driving the effect, modifying parental behavior should become the focus of intervention development. If adolescent psychopathology is driving the effect, preventing or treating youth disorders should become the focus of study.

Examination of adolescent/young adult relatives of BD probands provides an opportunity to study SUD/substance use and psychiatric disorders as they develop. Increased risk for SUDs in relatives of individuals with BD is hypothetically attributed to several factors. First, the occurrence of high rates of psychopathology in offspring of BD probands [26] may increase risk, as higher rates of SUDs have been associated with a range of mental disorders. Second, shared genetic loading for BD as well as SUDs is higher in relatives of BD probands. Identified genes likely influence affective and reward brain circuitry abnormalities linked with both SUD and BD [27]. Third, stressors associated with having relatives with BD may also increase risk for SUDs [28].

Several recent studies have reported on rates of SUDs in offspring of BD probands. In a Canadian sample, 24% of prospectively followed adolescent and young adult offspring of BD probands (aged 12–25) were found to have lifetime SUD, with cannabis being the most common substance abused [29]. Being male and having a prior mood disorder were risk factors for offspring developing a SUD [29]. Similarly, in the Dutch Bipolar Offspring Study, lifetime prevalence of a SUD was 28% in offspring of BD probands, when assessed at follow up during young adulthood [30]. BD in parental probands has also been shown to predict offspring SUD, while MDD in parental probands in the same sample did not [31]. SUDs and substance use are relatively common in the general adolescent population [32]; thus, comparisons with relatives of control proband parents are warranted in order to determine if their SUD rates differ from relatives of control probands whose families do not have identified BD. The Pittsburg Bipolar Offspring Study (BIOS) reported that 20% of relatives of BD probands had SUDs at follow up at mean age of 18.1 years, compared to only 10% of community control relatives of control probands [33]. In sum, SUD rates in young adult relatives of BD probands range from 20 to 28% and appear to be greater than those in relatives of control probands. However, while high rates of comorbid psychiatric and SUDs have been established, the relative influence of proband SUDs/psychopathology and relatives own psychopathology on SUD outcomes in relatives of probands with BD has not been well characterized in prior studies.

The relationship between parental/relative BD and SUDs and adolescent psychopathology and SUDs remains poorly defined. We hypothesize, for our primary research question, that offspring/relatives of probands with BD (“relatives of BD probands”) will be more likely to manifest SUDs, compared to youth offspring/relatives of control probands (“relatives of control probands”), even after adjusting for relative mental health diagnoses. We also report three exploratory analyses, hypothesizing that: (1) Parental SUDs, Parental BD and relative psychopathology will all be associated with increased odds for adolescent substance outcomes (2) Given the controversy surrounding the ages of onset of SUDs vs BD (e.g., some studies suggested that SUDs predict mood disorders [34], [35], [36] and others the reverse relationship [37], [38], [39], with most conceding that a bidirectional relationship is also likely), we plan to study the relative age of onset of each type of disorder and predict the onset of mood disorders will occur prior to the onset of SUDs in both groups, given the relatively earlier emergence of these disorders, in general. (3) Finally, we are unaware of any studies examining the relative age of onset of SUDs in BD relatives vs. control relatives. We predict that relatives of BD probands will have earlier onset of SUDs than relatives of control probands, given greater rates of child and adolescent onset psychopathology in BD relatives. To address these four topics, we examined the lifetime prevalence and age of onset of SUD outcomes and their relationship to parental SUDs and BD and comorbid youth psychopathology (i.e., mood, anxiety and externalizing disorders) in adolescent and young adult offspring/relatives of probands with and without BD. Given the young age of our sample, we examine the spectrum from subthreshold SUD symptoms to SUDs.

Section snippets

Subjects

As detailed in prior publications [26], [40], [41], information on participants was ascertained through the research database of the Bipolar High Risk Study Group. Relatives of BD probands were 12–21 year old offspring (81%) or siblings (9%) of a proband with BD, the majority of whom had BD, type I (89%). A small number (10%) were 2nd degree relatives of a BD proband in a family with multiple cases of BD. Control participants (“relatives of control probands”) were identified through proband

Results

Relatives of BD probands (mean age = 16.8 years; ± 2.9 S.D.) comprised 267 adolescent/young adult participants. This sample included subjects from 183 families, 121 with a single offspring, 44 with 2 offspring, 13 with 3, 2 with 4, 1 with 5, and 1 with 6. Males comprised 49.4% of this sample. There were 149 relatives of control probands (mean age = 17.4 years; ± 2.9 S.D.) ascertained from 114 families, 87 with a single offspring, 21 with 2 offspring, 5 with 3, and 1 with 5. Males made up 53% of this

Discussion

This study compared SUD development in young adult and adolescent relatives of probands with and without BD. Our primary finding was that rates of SUDs and substance use, except alcohol, were higher in relatives of BD probands compared to relatives of control probands, with offspring psychopathology appearing to partly account for such group differences in SUDs. We also found similar rates of SUDs compared to other studies on the offspring of BD probands [29], [30], [31], [33], with a lifetime

Conclusions

In summary, SUDs, PSU, SUDs and nicotine use were more common in relatives of probands with BD, with these differences largely accounted for by co-existing mood or externalizing disorders. These findings suggest that prevention and treatment of psychiatric disorders in adolescents may modify the course or prevent the development of SUDs, particularly in youth with a family history of BD.

The following are the supplementary data related to this article.

Acknowledgment

This work was supported by K12DA000357 to Leslie Hulvershorn and Collaborative R01s MH68009, MH073151, and MH068006 to John Nurnberger, Wendy Reich (later Anne Glowinski), and Melvin McInnis (with a subcontract to Johns Hopkins University) and colleagues.

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