Childhood-onset bipolar disorder is frequently associated with or preceded by oppositional defiant disorder, conduct disorder or, more frequently, ADHD [40,48,50,51]. The reasons for the association between bipolar disorder and ADHD remain unresolved. It is presently unclear whether this association is a true comorbidity, or a consequence of a diagnostic overlap between the two disorders, or if ADHD is a prodromal condition in the course of bipolar disorder, or a complication of bipolar disorder. Several studies support the finding that adolescent-onset bipolar disorder shows less comorbidity with disruptive behaviour disorders than prepubertal-onset bipolar disorder [40,48,52]. More recently, ADHD has been found as an antecedent in 50% of patients with prepubertal bipolar disorder, compared to 8.7% of patients with adolescent-onset bipolar disorder , suggesting that ADHD may be an antecedent or an early sign of a very early-onset bipolar disorder.
Wozniak et al.  interviewed 46 first-degree relatives of 16 children with a diagnosis of mania. High rates of ADHD comorbidity were found both in the proband children and in the relatives. A five-fold elevated risk for bipolar disorder was observed among relatives of children with ADHD and bipolar disorder, compared to children with ADHD alone . Furthermore, ADHD and bipolar disorder co-occurred in the same relatives more frequently than expected by chance.
Offspring studies on bipolar probands show that about a quarter of bipolar offspring meet criteria for ADHD [9,16-21]. High rates of ADHD in bipolar offspring may be related to an eventual early-onset of bipolar disorder in this population. The presence of ADHD with co-occurring mood difficulties in bipolar offspring may indicate an increased risk for bipolar development.
Carlson and Weintraub  grouped bipolar offspring, offspring of parents with other mental disorders and healthy controls by the presence or absence of behavioural or attentional problems, and found that these problems predicted the development of mental disorders in late adolescence or young adulthood. However, attentional and behavioural disorders were associated to later development of mood disorders in bipolar offspring, but not in offspring of parents with other disorders and in healthy controls .
Chang et al.  reported on the psychopathological features of 60 bipolar offspring. ADHD was the most frequent diagnosis (27%). Parents with bipolar disorder who reported to have had an ADHD during childhood more frequently had a child with bipolar disorder than bipolar parents without a history of ADHD [21,53]. Therefore, co-occurring ADHD and bipolar disorder in a parent may increase the risk for early-onset bipolar disorder in offspring.
Significantly lower rates of ADHD are reported in the offspring of bipolar patients in several non-US studies. Duffy et al.  found only one child with ADHD in the 21 offspring of 13 bipolar parents, and one child with ADHD in the 53 offspring of 30 bipolar probands in the expansion of the same study . This finding was supported by the lack of evidence of attentional problems in both affected and nonaffected children, irrespective of the parents' lithium responsiveness . In Wals et al.'s study , ADHD was a current diagnosis in 4% of the sample, and a lifetime diagnosis in 5% of the sample.
Given the symptomatological overlap, as well as the developmental relationship between ADHD and early-onset bipolar disorder, a comparison between the offspring of parents with ADHD and of bipolar parents with or without ADHD may help to clarify the relationship between bipolar disorder and ADHD .
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