A familial relationship between attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) was examined in 140 children with ADHD, 120 non-ADHD controls, and their 822 first-degree relatives by analyses of structured psychiatric interviews at the Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA. Of 15 ADHD+BPD children meeting diagnostic criteria for BPD, most had irritable, not euphoric, mood, only one had classic biphasic illness and 9 had mixed manic and depressive presentations. Relatives of both ADHD with, and without, BPD groups had an increased risk of ADHD compared to the non-ADHD controls. The risk of BPD among relatives was increased 5-fold if the proband child with ADHD had BPD. Relatives of ADHD+BPD probands had an increased risk of major depression. Both ADHD and BPD occurred in the same relatives more often than expected by chance. A male preponderance of bipolar relatives of ADHD+BPD probands was 75% to 25% female. A familial distinct subtype of comorbid ADHD with BPD is suggested by the data. 
COMMENT. The comorbid presentation of ADHD with BPD may represent a subtype nosologically discrete from other ADHD cases, a male predominant syndrome with childhood onset and severe symptomatology, and high familial risks for ADHD, BPD, and major depression.
The hypothesis that BPD may underly the syndrome of ADHD or occur as a comorbid disorder is not new. It was a popular explanation by some psychiatrists for the “hyperactive child” syndrome or the “minimal brain dysfunction” syndrome during the 1960’s, not generally subscribed to by neurologists specializing in the field. Werry JC, in his discussion of the above article by the Harvard group of investigators, points out that the data show a low association of ADHD and BPD, probably only 5%, and cautions against the risk of an overdiagnosis and treatment of ADHD as BPD, or as a comorbid disorder.
Mania with pervasive developmental disorder is reported in 14 children, representing 21% of a group of PDD subjects, in a study at the Massachusetts General Hospital . According to the authors, comorbid mania among patients with PPD may be more common than previously thought.
Symptoms of mania can include an abnormal and persistently elevated, expansive, or irritable mood, hyperactivity, distractibility, inappropriate cheerfulness, excessive talking, and silliness, sleeplessness, agitation, and aggressive outbursts. Adults with manic episodes also engage in inappropriate business ventures, unrestrained buying sprees, and irresponsible credit card debt.
Aggression in boys with ADHD was associated with parent aggressive behavior and lower 5-HT, central serotonergic function in a study of 41 boys at Queens College, Flushing, NY . Serotonergic function was assessed by the prolactin response to fenfluramine challenge.