Bipolar disorder is a dynamic condition characterized by cycling among emotional extremes. The dynamic expression of bipolar disorder suggests that its neurophysiology involves dysfunction of brain networks that maintain emotional homeostasis, i.e. the 'anterior limbic network.' Additionally, activation of the anterior limbic network may disrupt function of attentional brain regions, leading to cognitive symptoms. Previous imaging studies in bipolar disorder reported abnormalities throughout the anterior limbic network. Moreover, in preliminary work we found that, compared with healthy subjects, euthymic bipolar patients demonstrated abnormally increased activation throughout this network during an attentional task. It may seem counter-intuitive to use attentional tasks as probes to study brain activation in bipolar disorder. However, reciprocal activation between cognitive and emotional brain networks suggests that cognitive probes may identify inappropriate emotional network activation in bipolar patients. We will use fMRI and cognitive probes to determine whether anterior limbic network dysfunction causes a loss of homeostatic control of emotional behavior, leaving bipolar patients vulnerable to mood cycling. We specifically hypothesize that anterior limbic dysfunction persists throughout the course of bipolar illness, although, as a corollary we hypothesize that during euthymia, compensatory cortical activation occurs, which is absent during mood episodes. To test these hypotheses, 144 bipolar patients will be recruited when manic and will be followed for up to one year. Brain activation will be measured with fMRI while performing cognitive tasks during mania, following recovery (i.e., during euthymia), and at the time of depressive relapse. Comparisons with healthy subjects and across mood states (within subjects) will permit tests of our major hypotheses. If these hypotheses are supported, then anterior limbic dysfunction could provide a useful endophenotype to identify individuals at risk for bipolar disorder. Clarifying the dysfunction of these brain networks may permit translation of molecular findings into understanding the clinical expression of bipolar disorder. Moreover, defining dysfunction within the anterior limbic network in bipolar disorder could provide a target for treatment development. Finally, this work will provide a neurophysiologic substrate to inform additional investigations aimed at identify mechanisms underlying anterior limbic dysfunction both in human and animal models.
| Cerullo, Michael A; Eliassen, James C; Smith, Christopher T et al. (2014) Bipolar I disorder and major depressive disorder show similar brain activation during depression. Bipolar Disord 16:703-12 |
| Cerullo, Michael A; Strakowski, Stephen M (2013) A systematic review of the evidence for the treatment of acute depression in bipolar I disorder. CNS Spectr 18:199-208 |
| Cerullo, Michael A; Fleck, David E; Eliassen, James C et al. (2012) A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord 14:175-84 |
| Fleck, D E; Eliassen, J C; Durling, M et al. (2012) Functional MRI of sustained attention in bipolar mania. Mol Psychiatry 17:325-36 |
| Lisy, Megan E; Jarvis, Kelly B; DelBello, Melissa P et al. (2011) Progressive neurostructural changes in adolescent and adult patients with bipolar disorder. Bipolar Disord 13:396-405 |
| Fleck, David E; Kotwal, Renu; Eliassen, James C et al. (2011) Preliminary evidence for increased frontosubcortical activation on a motor impulsivity task in mixed episode bipolar disorder. J Affect Disord 133:333-9 |
| Strakowski, Stephen M; Eliassen, James C; Lamy, Martine et al. (2011) Functional magnetic resonance imaging brain activation in bipolar mania: evidence for disruption of the ventrolateral prefrontal-amygdala emotional pathway. Biol Psychiatry 69:381-8 |
| Cerullo, Michael A; Adler, Caleb M; Delbello, Melissa P et al. (2009) The functional neuroanatomy of bipolar disorder. Int Rev Psychiatry 21:314-22 |
| Strakowski, Stephen M; Adler, Caleb M; Cerullo, Michael A et al. (2008) MRI brain activation in first-episode bipolar mania during a response inhibition task. Early Interv Psychiatry 2:225-233 |
| Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M (2006) Brain network dysfunction in bipolar disorder. CNS Spectr 11:312-20; quiz 323-4 |
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