Fronto-Limbic Brain of Bipolar Children and Adolescents

在成人神经影像学研究中，参与情绪调节的额边缘脑（FLB）区域异常与双相情感障碍（BD）有关。这些FLB变化是随着BD的发展而发展的，还是在BD发展的早期就出现了？后者表明：(1)脑成熟过程中的发育异常可能导致这些FLB变化。如果是这样的话，那么(2)在疾病过程早期减少或缓解这些大脑变化的治疗可能会降低双相障碍的严重程度。为了验证这些假设，我们将在青春期后患有双相障碍的青少年（12-17岁）中进行一项联合体内神经影像学和临床干预试验（BD青少年），这将检查(a) FLB异常，(b) BD进展和严重程度，以及(c)对情绪稳定药物（丙戊酸盐）的反应之间的关系。我们将研究60例未经治疗的BD

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.