Etiology and pathophysiology
Heritability for PBD is substantially high with a rate of 15% to 42% risk in first-degree relatives of children with PBD.11 There is some evidence to indicate gene linkages with the brain-derived neurotrophic factor (BDNF) gene (Vall66), the glutamate decarboxylase 1 (GAD1) gene (4s2241165), and the dopamine(Drug information on dopamine) transporter gene (rs41084). However, none of these associations has been replicated and the sample sizes in these studies significantly limit the detection of small effects.11 Furthermore BDNF in platelets has been shown to be decreased in PBD and increased with treatment.12
Although the pathophysiology of PBD remains unknown, MRI studies during the past 5 to 10 years have significantly advanced scientists’ understanding of the brain mechanisms related to PBD symptoms and associated impairments. Structural and functional studies have all shown frontostriatal and frontolimbic abnormalities relative to healthy controls. A consistent structural finding is a small amygdala.13 There are extensive abnormalities in other related brain regions; overall findings implicate abnormalities in regions of the cognitive, emotional, and reward systems.14,15 White matter tract integrity is affected in the prefrontal regions of the corticobulbar tracts in patients with PBD relative to healthy peers.16
A 3-year longitudinal study demonstrates that neurocognitive deficits persist in PBD and show no change during the 3 years in the areas of executive function and verbal memory. While there is improvement in working memory and attention, children with PBD do not catch up with their healthy peers.14 It is important to evaluate whether there are academic difficulties related to poor neurocognitive abilities.
Assessment and diagnosis
Assessment and diagnosis of PBD have also advanced rapidly during the past 15 years. Whereas the notion of diagnosing bipolar disorder in childhood has been plagued by controversy in the past, the literature base to date has led to a consensus that PBD represents a discrete cluster of symptoms that can be validated by reliable assessment.17 The question remains as to how to best classify and describe the heterogeneity in clinical presentation seen in children with early-onset bipolar disorder.
The diagnosis of PBD is complex and requires an in-depth evaluation of the current presenting problem, as well as a history of mood episodes during the child’s lifetime to assess chronicity and episodicity. A clinical interview for making a diagnosis is still the gold standard. In research, however, a diagnostic clinical interview (eg, Washington University in St Louis Kiddie Schedule for Affective Disorders and Schizophrenia [WASH-U-KSADS] or Kiddie-SADS–Present and Lifetime Version [K-SADS-PL]) is often supplemented by an in-depth developmental history and multi-informant clinical rating scales to determine global functioning, social and academic impairment, and quality-of-life issues.
Screening measures can be used preliminarily to assess the presence of different types of manic symptoms. The Child Mania Rating Scale–Parent version (CMRS-P) is the first rating scale that was designed and tested specifically to screen for PBD.18 This measure has 21 developmentally specific items corresponding to DSM-IV-TR–based symptoms. A score of 15 or more (of a potential total score of 63) indicates a 92% chance of having PBD. The CMRS-P is a screening instrument with excellent psychometric properties and is available in 12 languages. It is intended to facilitate early identification of PBD with the hope of aiding parents who seek help for their child, but it is not a diagnostic tool.
Once a formal diagnosis of PBD is made, additional evaluation is needed to address systemic problems through psychosocial treatment that complements pharmacotherapy. Issues include:
• The level of distress of the patient and the family
• Knowledge, skills, and attitude of parents
• The child’s school functioning and neurocognitive problems
Bipolar I disorder is diagnosed if a child manifests abnormally elevated mood, grandiosity or inflated self-esteem, extreme irritability, hypersexuality (not explained by a history of sexual abuse), decreased need for sleep, and behavioral activation (characterized by agitation and pressured speech) coupled with poor judgment. Elevated mood, grandiosity, and irritability are the core symptoms of mania. While there is some debate about which of these is most central to a bipolar I disorder diagnosis, irritability interspersed with rage episodes tends to be the most readily identified and problematic for parents.