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Comorbidity in Bipolar Disorder: Page 4 of 5

Comorbidity in Bipolar Disorder: Page 4 of 5

Not withstanding this ambiguity and the lack of large epidemiological studies, there is general agreement regarding the co-occurrence of BPD and ADHD.47 In a recent review, Singh and colleagues48 found a bidirectional relationship between the 2: ADHD occurred in up to 85% of children with BPD, and BPD occurred in up to 22% of children with ADHD. The authors further explored 4 hypotheses:

• BPD symptoms lead to overdiagnosis of ADHD in youth.

• ADHD is a prodromal or early manifestation of childhood BPD.

• ADHD is treated with psychostimulants that trigger the onset of childhood BPD.

• ADHD and BPD share an underlying biological mechanism (ie, common familial, genetic, or neurophysiological).

Despite limitations, current literature best supports the second hypothesis—that ADHD may be a marker of the development of early-onset BPD. Ultimately, longitudinal controlled studies are needed to help us diagnose this disorder more precisely and to manage it rationally. Pharmacological studies may offer insights into the efficacy of mood stabilizers and/or the failure of psychostimulants; conversely, the induction of bipolar symptoms with psychostimulants or antidepressants may also be instructive.

Personality disorders

As with the comorbid conditions discussed earlier, the presence of a comorbid personality disorder complicates diagnostic interpretation and treatment decisions.49 Marked personality disorder–related symptoms may also negatively influence the outcome of the bipolar illness.50 The severity of residual mood symptoms in bipolar patients with personality disorders differs from that in bipolar patients without personality disorders—even during periods of remission.49

Features of a personality disorder may overlap with a bipolar mood episode.51 It may therefore be too challenging to diagnose a personality disorder until the mood episode has been successfully treated. A careful personal and collateral history may be most instructive in establishing the presence of personality traits that predate the onset of a discreet mood disturbance. Conversely, personality features that endure after the resolution of a mood episode may reveal the comorbid condition. A positive family history of a mood disorder and antidepressant-induced mood elevation also serve as important clues.

A recent study found that cluster B (borderline, narcissistic, antisocial, histrionic) personality disorder features were evident in about one-third of bipolar patients, with possible associations to childhood emotional and/or physical abuse.52 An independent, elevated lifetime risk of suicide was attributed to cluster B comorbidity. Recent literature advocates a more careful approach to diagnosing borderline personality disorder in the face of the mood-cycling pattern seen in bipolar II disorder; a cyclothymic temperament has been proposed as the underlying feature of this atypical mood, anxiety, impulsivity continuum.53,54

Clearly, treatment of this comorbid subtype requires a greater degree of finesse in the integration of psychotherapeutic and psychopharmacological modalities—especially in restoring functionality and ensuring compliance. Again, mood stabilization with lithium appears less effective than anticonvulsants, such as valproate or lamotrigine, in this comorbid population.55-57 Second generation antipsychotics (olanzapine, risperidone) have also played a role in improving symptoms and regulating affective lability.58-61

Medical comorbidities

Cardiovascular disease, type 2 diabetes mellitus, and other endocrine disorders tend to occur more often in patients with BPD than in the general population.62,63 According to population-based studies, cardiovascular mortality is almost twice as high in patients with BPD, which may be related to higher rates of obesity.5,64 Mechanisms hypothesized to explain this finding include smoking, diet, sedentary lifestyle, and unrecognized risk factors (insulin resistance, inflammation, hypercortisolemia).65,66

Comorbid neurological disorders, including migraine headache, have also been reported at higher rates in patients with BPD, especially bipolar II disorder. The latter may represent a subtype of the disease.67


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