This grant application is for 5 years of funding through the Mentored Patient Oriented Research Career Development Award (K23) program. The objective is to develop the candidate's skills in behavioral genetics research and augment her training in neurobiological endophenotypes of bipolar disorder. The research plan builds on the candidate's experience in behavioral endophenotypes and neurocognition in major mental illness (schizophrenia and bipolar disorder); its basic aim is to assess familial aggregation of measures of neurocognitive function, temperament, and neuroanatomy in unaffected relatives of individuals with severe bipolar disorder, and apply these measures to quantitative trait loci (QTL) analysis. The proposed study will provide an important first step toward the ultimate goal of linking bipolar endophenotypes to specific genes. Both the research and training plan are opportunistic, utilizing previously ascertained study samples from ongoing research, and renowned investigators in the UCLA research community. The Career Development Plan will develop the Pi's skills in: 1) the design of studies that collect and analyze human genetic material, 2) data analytic methods used to examine genetic effects on cognition and neuroanatony, and 3) analysis of quantitative trait loci. Methods of career development include: 1) the proposed study, 2) the mentorship of Drs. Nelson Freimer and Tyrone Cannon , 3) consultation with experts in behavioral and statistical genetics, 4) formal coursework in statistical genetics methodology and brain mapping, 5) attendance at scientific meetings, and 6) data preparation for submission of manuscripts to peer-reviewed journals. Given the candidate's prior training, proposed mentorship, outstanding resources and research environment, a K23 award will allow her to become a successful and independent investigator in the genetics and neurobiological bases of bipolar disorder. ? ?
| Hibar, D P; Westlye, L T; Doan, N T et al. (2018) Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group. Mol Psychiatry 23:932-942 |
| Pagani, Lucia; St Clair, Patricia A; Teshiba, Terri M et al. (2016) Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder. Proc Natl Acad Sci U S A 113:E754-61 |
| Hibar, D P; Westlye, L T; van Erp, T G M et al. (2016) Subcortical volumetric abnormalities in bipolar disorder. Mol Psychiatry 21:1710-1716 |
| Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel et al. (2015) Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder. Brain 138:2087-102 |
| Jalbrzikowski, Maria; Sugar, Catherine A; Zinberg, Jamie et al. (2014) Coping styles of individuals at clinical high risk for developing psychosis. Early Interv Psychiatry 8:68-76 |
| Golembo-Smith, Shana; Bachman, Peter; Senturk, Damla et al. (2014) Youth-caregiver agreement on clinical high-risk symptoms of psychosis. J Abnorm Child Psychol 42:649-58 |
| Fears, Scott C; Service, Susan K; Kremeyer, Barbara et al. (2014) Multisystem component phenotypes of bipolar disorder for genetic investigations of extended pedigrees. JAMA Psychiatry 71:375-87 |
| Jalbrzikowski, Maria; Krasileva, Kate E; Marvin, Sarah et al. (2013) Reciprocal social behavior in youths with psychotic illness and those at clinical high risk. Dev Psychopathol 25:1187-97 |
| Lombardo, Lauren E; Bearden, Carrie E; Barrett, Jennifer et al. (2012) Trait impulsivity as an endophenotype for bipolar I disorder. Bipolar Disord 14:565-70 |
| Bearden, Carrie E; Karlsgodt, Katherine H; Bachman, Peter et al. (2012) Genetic architecture of declarative memory: implications for complex illnesses. Neuroscientist 18:516-32 |
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