On the whole, the rates of comorbid anxiety disorder in our substance-dependent bipolar population were nearly three times those reported in the general bipolar population (McElroy et al. 2001
). These results are supported by previous findings showing that bipolar patients with substance dependence are up to four times more likely to be diagnosed with Axis I disorders (Sonne et al. 1994
), but they are the first (to our knowledge) to show that these comorbid disorders are related to the type of substance on which a bipolar patient is dependent.
Alcohol dependent participants were significantly more likely to have comorbid generalized anxiety disorder than the cocaine dependent participants, while cocaine dependence was associated with significantly higher prevalence rates of ASPD and PTSD. In addition to the type of comorbid Axis I and Axis II disorders, clinical features of the bipolar patients were also related to the type of substance dependence in our study population. Alcohol dependence was associated with the depressed mood state, while cocaine dependent participants were more likely to have a mixed mood state and Bipolar I diagnosis than alcohol dependent participants.
The association between cocaine dependence and both ASPD and PTSD in bipolar disorder is consistent with previous research (Regier et al., 1990
and Kolodziej et al. 2005
). Since cocaine induces anxiety, a link between cocaine dependence and anxiety disorders is not unexpected. In addition, PTSD has been shown to develop in cocaine use disorder perhaps due to trauma associated with the use and procurement of cocaine, although cocaine use disorder can also occur secondary to PTSD (Brady et al. 1998
). ASPD is also congruent with the adverse behavior associated with cocaine use.
In contrast to ASPD and PTSD, GAD was more prevalent in bipolar disorder with alcohol dependence than in bipolar disorder with cocaine dependence. The National Comorbidity Survey also found a significantly higher 12-month co-occurrence of GAD with alcohol dependence than GAD with drug (other than alcohol) dependence (Kessler et al. 1996
). This association may arise from the notion that alcohol can be “therapeutic” for anxiety. Some studies have suggested that substance dependence can originate from an attempt to treat a mental disorder (Sonne et al., 1994
and Weiss et al., 2004
Conversely, while substance dependence may begin in an effort to self-medicate, Maremmani has suggested in a recent review that bipolar patients with substance use often continue to use substances even after the substance fails to continue to provide symptom relief (Maremmani et al., 2006
). He suggests that dependence in individuals with bipolar spectrum disorders may be better explained by (hypo)manic excitement, which leads to both sensation seeking behavior and a failure to appreciate its consequences (Maremmani et al., 2006
). (Hypo)mania – the core trait of the bipolar spectrum – also becomes the driving force behind the addiction. This idea suggests that substance abuse and bipolar disorder may be more than simply comorbid disorders, and may actually arise from a common diathesis. Similarly, GAD and alcohol dependence or ASPD, PTSD and cocaine dependence may be linked clinically simply because they arise from common temperament or personality traits.
Lara and colleagues recently proposed a bidimensional model based on fear and anger traits to explain the comorbidity of mood, behavior, and personality disorders (Lara et al., 2006
). Fear was used to encompass pessimism, fear of uncertainty, timidity and low energy, while anger included goal-directed exploration and appetitive impulsivity. They proposed that fear was the basis of depression and anxiety disorders, while both ASPD and PTSD were linked to high levels of anger. This hypothesis could be extended to suggest that alcohol dependence is linked to high fear traits, and cocaine dependence derives from high anger traits.
In our study, those with alcohol dependence were more likely to present in the depressed phase (high fear) of bipolar illness. Cocaine dependence was in turn associated with higher rates of mania (high anger) and mixed states. Alcohol has long been linked to depression, and it has even been found that a past diagnosis of alcohol dependence was associated with more than a 4-fold increase in risk of current or recent (last 12 months) major depressive disorder (Hasin and Grant, 2002
). The association between cocaine dependence and mania is more complex, since cocaine can induce mania. Conversely, Camacho and Akiskal have suggested that the temperamental inclination to bipolar disorder, and the social stressors related to that temperament, may be the driving factors leading to stimulant use and abuse (Camacho and Akiskal, 2005
). Bipolar patients have also been reported to increase stimulant use during mania in order to accentuate the manic high (Strakowski and Delbello, 2000
). Regardless of the primary etiology, it is possible that a state of high anger leads to both stimulant abuse and mania.
An advantage of the bidimensional model is that the basic fear and anger traits are mostly independent of each other. By design, this tenet accounts for the observation that apparently paradoxical states, such as depression and mania, can coexist (Lana et al., 2006). It also suggest that a person with both alcohol and cocaine dependence would be susceptible to the combined set of comorbid disorders. Indeed, those in the ETOH + COC group were significantly more likely to be diagnosed with PTSD and ASPD than those in the ETOH group. The ETOH + COC group tended towards a higher prevalence of GAD than the COC group, although the result was not significantly different. This comparison was likely hampered by the small size of the COC group.
The study has several limitations. Data was initially collected for the purpose of clinical trials and not for the purpose of a well-designed epidemiological study. Temperament was not assessed, and the MINI diagnostic interview does not assess for lifetime comorbidities except for panic disorder and antisocial personality disorder. Lifetime rates would better reveal long-term relationships among the disorders. Medication being taken by patients at baseline could have also affected the rates of comorbidity found. Participants were drawn from those entering three clinical trials instead of just one study, though the research assistants from all three trials received the same training in conducting the MINI, and a secondary interview with a certified psychiatrist was always used. Relative to the local demographics, our patient sample over-represented Caucasians and under-represented Asians and Hispanics. Thus, the generalizability of the findings may be limited.
The study reinforces the previous finding of a high prevalence of personality and anxiety comorbidity in the substance dependent, bipolar population. Such an association is noteworthy, since comorbid personality and anxiety disorders exacerbate bipolar disorder even without the negative effects of substance abuse (Young et al., 1993
; Carpenter et al., 1995
; Ucock et al., 1998; Dunayevich et al., 2000
; Feske et al., 2000
; George et al., 2003
). Given the implications for the management of patients with bipolar disorder and concurrent substance, anxiety, and/or personality disorder, care should be taken to identify comorbid psychiatric illness in any patient population. Unfortunately, bipolar disorder is itself frequently underdiagnosed in the substance dependent population (Albanese et al., 2005).
This study helps support the theory that a person’s expression of comorbid personality, anxiety, mood, or behavior disorders may result from a common, underlying diathesis. Further studies to define the order of development of these comorbid disorders are needed to elucidate any causal relationships and common susceptibilities.