Development of Cognitive Functions that depend on the Frontal Lobe in Children whose Mothers have Bipolar I Disorder

With Dr. Adele Diamond, Dr. Allan H. Young, Dr. E. Jane Garland, Dr. Karine McRitchie, Holly MacPherson, Annie Kwan, William Ma and Dr. Weihong Song

Both Unipolar (UD) and Bipolar Affective Disorder (BD) are associated with prefrontal cortex cognitive impairment. Although depressive symptoms and anti-depressive medication may exacerbate cognitive impairments, an abnormal cognitive profile has been reported from drug-free and euthymic depressive populations. Prefrontal cognitive impairment has been indicated as a potential endophenotypic marker (a measurable hereditary component associated with a disorder but is not a direct symptom of that disorder) for severe mood disorders. In first-degree relatives, and especially children of BD patients, the lifetime prevalence of severe affective disorders is very high. Children of mothers with BD are thus an ideal population in which to examine putative endophenotypic markers for the development of severe affective disorder.

Two recent preliminary studies have provided some support for this notion in high risk relatives. Decrements in cognitive functions dependent on the frontal lobe have also been observed in unaffected monozygotic co-twins of BD patients. However, the definitive study has yet to be done. We aim to investigate the nature of executive functioning (prefrontally-dependent cognitive functions) in children of BP I mothers and potentially as an endophenotypic marker of severe affective disorder. In addition, we will investigate circadian function as a candidate endophenotype for BD, and genetic polymorphysisms as co-variates which may explain variation in cognitive and/or psychiatric outcomes among subjects.

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