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318 REVERSIBLE DISORDERS OF BRAIN DEVELOPMENTet al., 2004). One reason for this decreasing AAO may be genetic anticipation.Anticipation refers to the phenomenon of a disease state occurring in successivegenerations with earlier ages of onset and/or higher severity. This phenomenonhas been described in other neurological disorders (e.g., Huntington’s, Fragile X,myotonic dystrophy), and in some cases it has been linked to genetic causes: thatof trinucleotide repeat sequences expanding in number of repeats with each generation(for review, see Goossens, Del-Favero, & Van Broeckhoven, 2001). Althoughgenetic repeat expansions have not been definitively linked to anticipationin BD, anticipation itself has been found to occur in cohorts of families with BD(Howe et al., 2004; McInnis et al., 1993). Studies of birth cohorts with BD inPennsylvania found that patients born after 1940 experienced their first moodepisode 4.5 years earlier in life than those born before 1940 (Chengappa et al.,2003). In a Northern California cohort of 57 families of parents with BD, the meanAAO of mania in the adults was 16.8 years, compared to 11.2 years for their offspringwith BD, a difference of 5.6 years between generations (Howe et al., 2004).However, it is unclear whether this anticipation is solely due to genetic reasons.Other possible reasons include better diagnostic skills of clinicians, heightenedpublic and professional awareness of the possibility of mood disorders in children,environmental effects such as growth hormone in milk leading to earlier onsetof puberty, and other exogenous factors such as the recent increase in use of stimulantsand antidepressants in youth (Reichart & Nolen, 2004). Whatever the cause,it now appears that most cases of BD begin in childhood or adolescence. Thereforeearly detection and intervention programs should be aimed at this age group.During childhood, the early symptoms of BD are often difficult to diagnosebecause they often do not fulfill the required criteria for a full mood episode.Premorbid symptoms also may vary from child to child, depending on the subtypeof BD, because BD is a fairly heterogeneous disorder with different subtypesincluded within the bipolar spectrum. For example, bipolar spectrum diagnosesin the DSM-IV include bipolar I and II disorder, cyclothymia, and bipolar disordernot otherwise specified (NOS). The classic form of manic-depressive illness,as described by Emil Kraeplin, is episodic in nature with periods of interepisoderecovery (Goodwin & Jamison, 1990). In this “classic” form, there may be nopremorbid symptoms before the first mood episode, often a first manic “break”occurring during late adolescence or early adulthood. Currently, this type of BDis thought to be less common than other more chronic and rapid-cycling forms,and forms that include irritability instead of euphoria as the primary manic mood(Akiskal, 1996). Adults with this type of BD commonly report that they experiencedsymptoms of depression, mania, suicidality, and so on, years before theirfirst manic episode (Lish et al., 1994). Therefore, in the majority of cases theremay be symptom complexes that predate the full expression of BD. Identificationof these complexes may help in determining populations at high risk forBD development.