Abnormalities in fronto-limbic brain (FLB) regions involved in mood regulation have been associated with bipolar disorder (BD) in neuroimaging studies on adults. Did these FLB changes develop as BD progressed, or did they emerge early during BD development? The latter would suggest that (1) developmental abnormalities in brain maturation processes may have led to these FLB changes. And, if so, then (2) treatments that reduced or alleviated these brain changes early in the disease process might reduce the severity of BD. To test these hypotheses, we will conduct a combined in vivo neuroimaging and clinical intervention trial in post-pubertal adolescents (ages 12-17 years old) who have BD (BD adolescents), that will examine the relationships between (a) FLB abnormalities, (b) BD progression and severity, and (c) response to a mood-stabilizing medication (valproate). We will study 60 untreated BD adolescents and 60 matched healthy controls. 30 BD patients will not have comorbid attention deficit hyperactive disorder (ADHD), oppositional defiant disorder (ODD), and/or conduct disorder (CD), while another 30 will have these comorbid conditions. Patients in both groups may also have comorbid anxiety disorders, with the exception of obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). The 60 patients will enter a 6-week open trial with valproate at therapeutic doses (as measured by serum valproate levels). Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) will be performed to compare brain anatomy (size of key FLB regions involved in mood regulation, with a focus on prefrontal cortex and amygdala) and neurochemistry (levels of N-acetyl aspartate (NAA), a non-specific marker of neuronal viability or function) across the 3 groups, as well as after treatment. Neuropsychological testing will also be conducted to evaluate specific FLB functions. This will be the first in vivo evaluation of FLB abnormalities in BD adolescents and in their response to treatment. It will contribute to elucidating the pathophysiologic mechanisms of BD, to understanding the mechanisms of action of mood stabilizers, and to identifying new endophenotypes of BD or biological targets that could aid in diagnosis, monitoring or treatment.
| Bauer, Isabelle E; Frazier, Thomas W; Meyer, Thomas D et al. (2015) Affective Processing in Pediatric Bipolar Disorder and Offspring of Bipolar Parents. J Child Adolesc Psychopharmacol 25:684-90 |
| Sanches, Marsal; Scott-Gurnell, Kathy; Patel, Anita et al. (2014) Impulsivity in children and adolescents with mood disorders and unaffected offspring of bipolar parents. Compr Psychiatry 55:1337-41 |
| Bauer, Isabelle E; Sanches, Marsal; Suchting, Robert et al. (2014) Amygdala enlargement in unaffected offspring of bipolar parents. J Psychiatr Res 59:200-5 |
| Caetano, Sheila C; Olvera, Rene L; Hatch, John P et al. (2011) Lower N-acetyl-aspartate levels in prefrontal cortices in pediatric bipolar disorder: a ¹H magnetic resonance spectroscopy study. J Am Acad Child Adolesc Psychiatry 50:85-94 |
| Zappitelli, Marcelo C; Bordin, Isabel A; Hatch, John P et al. (2011) Lifetime psychopathology among the offspring of Bipolar I parents. Clinics (Sao Paulo) 66:725-30 |
| Ogburn, Kelin M; Sanches, Marsal; Williamson, Douglas E et al. (2010) Family environment and pediatric major depressive disorder. Psychopathology 43:312-8 |
| Baloch, Hasan A; Hatch, John P; Olvera, Rene L et al. (2010) Morphology of the subgenual prefrontal cortex in pediatric bipolar disorder. J Psychiatr Res 44:1106-10 |
| Olvera, Rene Luis; Caetano, Sheila C; Stanley, Jeffrey A et al. (2010) Reduced medial prefrontal N-acetyl-aspartate levels in pediatric major depressive disorder: a multi-voxel in vivo(1)H spectroscopy study. Psychiatry Res 184:71-6 |
| Sanches, Marsal; Caetano, Sheila; Nicoletti, Mark et al. (2009) An MRI-based approach for the measurement of the dorsolateral prefrontal cortex in humans. Psychiatry Res 173:150-4 |
| Bellani, Marcella; Yeh, Ping-Hong; Tansella, Michele et al. (2009) DTI studies of corpus callosum in bipolar disorder. Biochem Soc Trans 37:1096-8 |
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