To the Editor: The clinical case conference by Jean A. Frazier, M.D., et al. (1) highlighted that diagnosing comorbid bipolar disorder in patients with Asperger’s disorder who display prominent affective symptoms is crucial so that these children can receive appropriate treatment. However, this is not a new observation and has already been made by me in a previous report (2). In addition to increasing awareness of the existence of such comorbidity in patients with Asperger’s disorder, I emphasized caution in prescribing psychotropic medications—especially antidepressants—to this population. Antidepressants, including selective serotonin reuptake inhibitors (SSRIs), have been shown to induce hypomania in some patients with Asperger’s disorder (3) and also to worsen aggressive behavior—the latter evident in the case study by Dr. Frazier and colleagues. Thus, when antidepressants are added to treat depression or repetitive stereotyped behavior in such patients, it may be worthwhile to add a mood stabilizer, particularly if there is a positive family history of affective illness.

A growing body of literature now suggests the effective use of mood stabilizers in autistic spectrum disorders with comorbid bipolar disorder. This use may stem from the common neurobiological substrates in these two conditions. Involvement of the amygdala in both of these disorders, as discussed by the authors, leads one to hypothesize as to whether mood stabilizers have a specific role in controlling the emotional dysregulation of Asperger’s disorder, which is often misinterpreted as a part of that disorder. Indeed, there is evidence to suggest that lithium and valproate may change genetic expression in the amygdalal-hippocampal complexes through modulating second-messenger effects (4). Further research in this respect would be encouraging.

Finally, in my observation, some patients with Asperger’s disorder with comorbid bipolar disorder require higher doses or a combination of mood stabilizers, which may be partly explained by the fact that bipolar disorder is recognized quite late in these patients, thus conferring some resistance to treatment. Hence, a clinician may have to adequately treat such patients with mood stabilizers at doses higher than those typically used in add-on regimens for control of aggressive or impulsive behavior.