Principal Investigator
Mani Pavuluri, MD, PhD

Major developmental changes take place in adolescence where brain maturation influences steep cognitive development and academic achievement critical for school functioning. However, Adolescent Bipolar Disorder (ABD) is a serious public health concern where abnormalities in brain circuitry function. Top down regulation of affective brain systems was illustrated in ABD by decreased activation of dorsolateral and ventrolateral prefrontal cortex and increased activation of amygdala while performing a cognitive task under emotional challenge. We also found worsening of neurocognitive functioning in the domains of attention, working memory and executive function over a three year period in ABD. Given these developmental abnormalities that are likely to impact ABD patients cognitive and affective functioning, it is particularly important to understand the brain maturational abnormalities influencing the affective and cognitive development pathophysiological processes affecting the underlying affective and cognitive neural systems at the onset of the illness and as they progress over the adolescence. Therefore, our first and central aim of the current study is to clarify the systems-level pathophysiology during manic states to better identify the interlinked affective and cognitive neural circuitry function. Our secondary aim is to examine the affective and cognitive circuitry function following symptomatic recovery.

We plan to use a longitudinal study design, examining brain function in 100 narrowly defined medication naïve PBD patients aged 13-16 years at two time points: (1) At baseline in manic state, and (2) After 8 weeks of treatment with the prototypic mood stabilizer lithium carbonate in medicated euthymic responders and non-responders. Additionally, at baseline and at the end of 8 weeks, we will also characterize the brain function in 50 typically developing IQ and demographically matched healthy youths who will be compared with the PBD patients. We will use innovative neurocognitive and fMRI paradigms to probe the affective and cognitive circuitry function at each time point. This work will help to establish a model that characterizes the functional pathophysiology of PBD and provides reliable and objective understanding of the neural systems in illness and on recovery. This model will serve as a prototype in providing future opportunities for preventive efforts by facilitating early identification, moving a step closer to safer, more effective and neurobiologically informed early interventions for youths that would potentially reverse the pathophysiology in PBD patients.

FUNDING: NIMH 5R01MH081019-02