Bipolar disorder (BP) is a progressive, life-threatening condition characterized by alternating episodes of severe depression and mania, ranked by the WHO as among the leading causes of lifetime disability. The heritability of BP is estimated at 85–95%, and genetic susceptibility loci, each with small effects, are emerging. Accumulating evidence suggests a developmental origin for BP: neuroanatomical abnormalities are often present at the first episode; there are organizational and neuronal migration alterations, with minimal astrogliosis. In addition, BP is typically diagnosed at adolescence when there is a shift from relying on earlier-developing brain regions to later-maturing prefrontal structures—a period when the brain may be particularly vulnerable to pre-existing neuropathologies (Strakowski, 2012). Since subtle changes in differentiation can produce neurological consequences that only become apparent much later in life, a developmental model to study BP is required.

The ability to reprogram adult somatic cells to induced pluripotent stem cells (iPSC) by expressing four transcription factors found in the blastocyst inner cell mass and embryonic stem cells (Takahashi et al, 2007) now makes it possible to derive BP patient-specific stem cells. iPSC are well suited to identify alterations in cell behavior, examine gene expression, and identify novel signaling pathways in the affected cell type(s). In BP, they provide a robust source of cells from individuals with longitudinal observations, individuals on or off medications, and patients who have comorbid diagnoses, multiple episodes and treatments, unlike embryonic stem cells. iPSC have been derived for other neuropsychiatric disorders (e.g., Brennand et al, 2011), and are now being reported for BP.

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