This is a renewal of the protocol entitled "Children of Bipolar Parents: A High-Risk Follow-up Study" (NIMH #60952) also known as the Bipolar Offspring Study (BIOS). In line with the current NIMH Strategic Plan, BIOS has been investigating the additive effects of behavioral, affective, circadian/sleep, genetic, and psychosocial factors associated with the development of mood disorders in the offspring of parents with bipolar disorder (BP). Enrollment of BIOS sample was completed in July 2007 with 862 children recruited (509 from parents with BP and 353 from community control parents) and a retention rate of 87%. Interviewers, blind to parental diagnosis, assessed offspring every other year with a comprehensive battery of instruments. BIOS is beginning to elucidate a specific developmental progression to bipolarity in the offspring of parents with BP and as to date, offspring of parents with BP are at significantly higher risk to develop BP-I (OR: 19.5) or subsyndromal BP (OR: 31.2). Since most of the sample will enter the age of highest risk to develop BP and other mood disorders during the next funding period, we are proposing to continue to study this sample for 5 more years. For a subset of 200 children of parents with BP and control parents, we propose to measure neurocognitive functioning and activity in, and functional and anatomic connectivity between, neural regions implicated in the pathogenesis of BP, and obtain more precise measurements of puberty using salivary hormonal levels. We hypothesize that, relative to offspring of control parents, offspring of parents with BP will develop over follow-up: 1) higher rates of mood disorders and psychopathology (e.g., mood lability, disrupted sleep) and 2) deficits in neurocognitive functioning and neurocircuitry associated with emotion processing and regulation. In addition, in offspring of parents with BP, onset of BP or any mood disorder will be predicted by the combined effects of development, demographic factors, other psychiatric disorders, dimensional behavioral and mood phenotypes, family environmental factors, and their interactions. Within the subset of offspring of parents with BP who will have neurocognitive and neuroimaging data, onset of BP or any mood disorder will be predicted by abnormal neurocognitive functioning and activity and connectivity in neural circuitry for emotion processing and regulation, that in turn will be associated with sleep and circadian factors, puberty, and clinical and demographic risk factors identified above. Findings from this large study will help identify the initial symptoms and neurobiomarkers related to increased risk of BP in youth. Such findings will facilitate prompt diagnosis and interventions, thus preventing, or at least ameliorating, the negative effects of this severe illness in youth.
Bipolar disorder is a severe illness associated with considerable negative consequences for the normal development of the child and increased risk for suicide and substance abuse. However, little is known about the initial symptoms and the progression of this illness from childhood and adolescence to adulthood. The findings from this large study will help to identify the initial symptoms and some brain biological markers related to the increased risk to develop bipolar in youth. Such findings will advance the field so that prompt diagnosis and interventions are made, thus preventing or at least ameliorating the negative effects of this severe illness in youth.
|Frank, E; Nimgaonkar, V L; Phillips, M L et al. (2015) All the world's a (clinical) stage: rethinking bipolar disorder from a longitudinal perspective. Mol Psychiatry 20:23-31|
|Maoz, Hagai; Goldstein, Tina; Axelson, David A et al. (2014) Dimensional psychopathology in preschool offspring of parents with bipolar disorder. J Child Psychol Psychiatry 55:144-53|
|Ballester, Javier; Goldstein, Benjamin; Goldstein, Tina R et al. (2014) Prospective longitudinal course of aggression among adults with bipolar disorder. Bipolar Disord 16:262-9|
|Maoz, Hagai; Goldstein, Tina; Goldstein, Benjamin I et al. (2014) The effects of parental mood on reports of their children's psychopathology. J Am Acad Child Adolesc Psychiatry 53:1111-22.e5|
|Sparks, Garrett M; Axelson, David A; Yu, Haifeng et al. (2014) Disruptive mood dysregulation disorder and chronic irritability in youth at familial risk for bipolar disorder. J Am Acad Child Adolesc Psychiatry 53:408-16|
|Phillips, Mary L; Swartz, Holly A (2014) A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. Am J Psychiatry 171:829-43|
|Purcell, Amanda L; Phillips, Mary; Gruber, June (2013) In your eyes: does theory of mind predict impaired life functioning in bipolar disorder? J Affect Disord 151:1113-9|
|Ladouceur, Cecile D; Diwadkar, Vaibhav A; White, Richard et al. (2013) Fronto-limbic function in unaffected offspring at familial risk for bipolar disorder during an emotional working memory paradigm. Dev Cogn Neurosci 5:185-96|
|Belleau, Emily L; Phillips, Mary L; Birmaher, Boris et al. (2013) Aberrant executive attention in unaffected youth at familial risk for mood disorders. J Affect Disord 147:397-400|
|Birmaher, Boris (2013) Bipolar disorder in children and adolescents. Child Adolesc Ment Health 18:|
Showing the most recent 10 out of 21 publications