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316 REVERSIBLE DISORDERS OF BRAIN DEVELOPMENTpotentially devastating effects. For example, if the first mood episode of a patientwith BD is depression, misdiagnosis of unipolar depression may lead to treatmentwith SSRIs, which could trigger mania or cause suicidality in patients with BD(Faedda, Baldessarini, Glovinsky, & Austin, 2004), Baumer et al., in press). Thereis also some concern about the chronic use of stimulants in children with or beforethe onset of BD. Because attention deficit/hyperactivity disorder (ADHD)commonly precedes pediatric-onset BD (K. D. Chang, Steiner, & Ketter, 2000;Faraone, Biederman, Mennin, Wozniak, & Spencer, 1997), the risk of premorbidstimulant therapy is very real. Thus, as will be discussed in this chapter, moreappropriate interventions, whether pharmacologic or psychotherapeutic, wouldobviate the possibility of this inappropriate treatment.Delay or Ameliorate Severity of Mania. If total prevention may not be possible,at least delay of onset of first manic episode seems likely. In a cohort of 60 childrenwith BD, who all had a parent with BD as well, age at onset (AAO) of maniawas 2–3 years later in children with prior exposure to either valproate or carbamazepine(p = .03) or lithium (p = .04) compared to those without such exposure (Changet al., 2006). This indirect evidence suggests that more appropriate early treatmentcould delay the first episode of mania. Amelioration might mean greater timebetween episodes, less severe mood symptoms, and prevention of suicidality andsuicide.Prevent Full Expression of BD. The theory of kindling is important to the conceptof prevention. First applied to seizure disorders, the theory holds that withthe combination of psychosocial stress and genetic vulnerability, greater destabilizationoccurs until a full mood episode occurs (figure 14-1; Post, 1992). Then,with each mood episode, the brain becomes sensitized, so that it becomes easierto have the next mood episode—until spontaneous episodes occur without the needfor psychosocial stress. Thus, patients with BD not properly treated would developepisodes closer to one another, with more severity, leading to rapid cyclingand more treatment resistance (Post & Weiss, 1996). This naturally progressivecourse has not been proven, as it is difficult and unethical to conduct such a long,controlled longitudinal study with one subset of participants receiving no treatment.Nevertheless, retrospective reporting from patient histories (Roy-Byrne,Post, Uhde, Porcu, & Davis, 1985) and research at the level of the cell (Post, 1992)support this hypothesis.Interventions early in the course of kindling may reverse the illness course.For example, rats given repeated subseizure-level electrical stimulation to theiramygdalae will eventually develop seizures, leading to a spontaneous seizure disorder.However, if the same rat is administered valproate early on, no seizure disorderwill ever develop (Post, 2002). Thus, if similar interventions are performedearly enough in bipolar illness development, it is possible that the full expressionof BD could be completely averted.