There is evidence to suggest that bipolar disorder consists of multiple distinct subtypes. One measure that appears to stratify some of these subtypes is age at onset (Faraone et al., 2003; Potash et al., 2007). The enrichment of inherited or de novo CNVs in subjects with an early onset of mania (Malhotra et al., 2011; Priebe et al., 2011; Zhang et al., 2009a) is consistent with the notion of distinct subtypes and suggest that individuals with an early onset of mania might constitute a subclass of bipolar disorder in which there is a greater contribution from rare alleles of large effect. Also consistent with this notion, a previous study found that segregation of early-onset bipolar disorder in families was consistent with major gene effects, whereas familial segregation of late-onset bipolar disorder was consistent with a multifactorial etiology (Grigoroiu-Serbanescu et al., 2001).
