Panic disorder occurs in about 1 in 5 individuals who have bipolar disorder. Anxiety amplifies the distress caused by depression and mania, but pharmacological approaches are tricky and under-studied. Frequent comorbidity and evidence of a possible genetic relationship of bipolar and panic disorders are suggestive of a causal relationship between the 2. Thus, it may be fruitful to look more closely at evidence for common biological abnormalities in both disorders to find a pathophysiological mechanism that links mania, depression, and panic attacks. Mood episodes and panic attacks can both be modeled as the result of deficits in amygdala-mediated emotional conditioning.1 From this model, some insight may be gained for potentially helpful treatment strategies for the 2 disorders when they occur together.
Evidence for comorbidity
In nearly every study, substantial numbers of individuals who meet criteria for bipolar disorder—between 15% and 20%, or 10 to 20 times the rate in the general population—also meet criteria for panic disorder.2-5 Others have found more modest elevations in the rate of panic disorder in persons with bipolar disorder.6 A relationship between bipolar and panic disorders has also been recorded when looking from the opposite direction. Anxiety disorder specialists have long noticed high rates of bipolar spectrum disorders in their patients who have panic disorder.7
Clinical presentation and consequences of comorbidity
Symptoms of panic disorder have been associated with greater suicidality in patients who have bipolar disorder.8-10 Panic disorder has predicted a slower treatment response in bipolar disorder,9,11 as well as greater likelihood of substance dependence and other anxiety disorders.4 Panic disorder is associated with more unstable forms of bipolar illness—namely, mixed, rapid-cycling, or rapid-switching states.12,13 Findings from a study of intraepisodic panic attacks in hospitalized patients with bipolar disorder suggest that panic attacks are extremely common—affecting as many as 60% of patients—in bipolar, depressed, and mixed states but are relatively uncommon in patients with pure mania.14
Early-age-at-onset samples tend to have more panic comorbidity than average,15 although elevated bipolar and panic comorbidity is documented throughout the life cycle, including in geriatric populations.16 There is less information on other clinical patterns of comorbidity. The question remains whether panic attacks in individuals with bipolar disorder are identical in form to panic attacks in others. It is also unknown whether panic attacks take a different form when they occur in the context of active mood symptoms or when they occur between mood episodes.
Family/genetic aspects of bipolar and panic comorbidity
The rate of panic comorbidity in family samples with bipolar disorder resembles the rate in population studies.17-18 In these studies, risk for panic disorder is elevated only in family members with a mood disorder. The results from analyses of 2 genetic databases reveal a specific familial risk for panic in some individuals with bipolar disorder.17,19
Molecular evidence of a common genetic risk factor for bipolar and panic disorders remains sparse. A stratified reanalysis of bipolar linkage data from 28 families, which had supported a genetic locus for bipolar disorder on the long arm of chromosome 18,20 revealed that the evidence for the link was carried almost exclusively by the families that had an elevated risk for panic disorder.21 This result remains in doubt, however, since it has not been replicated in other studies. A later study of 3 genes of possible functional relevance to bipolar disorder revealed that panic comorbidity enhanced the evidence of association for individuals with bipolar disorder but without panic disorder.22 This finding also awaits positive replication.
