OBJECTIVE: To examine abnormal patterns of frontal cortical-subcortical activity in response to emotional stimuli in euthymic individuals with bipolar disorder type I in order to identify trait-like, pathophysiologic mechanisms of the disorder. We examined potential confounding effects of total psychotropic medication load and illness variables upon neural abnormalities. METHOD: We analyzed neural activity in 19 euthymic bipolar and 24 healthy individuals to mild and intense happy, fearful and neutral faces. RESULTS: Relative to healthy individuals, bipolar subjects had significantly increased left striatal activity in response to mild happy faces (p < 0.05, corrected), decreased right dorsolateral prefrontal cortical (DLPFC) activity in response to neutral, mild and intense happy faces, and decreased left DLPFC activity in response to neutral, mild and intense fearful faces (p < 0.05, corrected). Bipolar and healthy individuals did not differ in amygdala activity in response to either emotion. In bipolar individuals, there was no significant association between medication load and abnormal activity in these regions, but a negative relationship between age of illness onset and amygdala activity in response to mild fearful faces (p = 0.007). Relative to those without comorbidities, bipolar individuals with comorbidities showed a trend increase in left striatal activity in response to mild happy faces. CONCLUSIONS: Abnormally increased striatal activity in response to potentially rewarding stimuli and decreased DLPFC activity in response to other emotionally salient stimuli may underlie mood instabilities in euthymic bipolar individuals, and are more apparent in those with comorbid diagnoses. No relationship between medication load and abnormal neural activity in bipolar individuals suggests that our findings may reflect pathophysiologic mechanisms of the illness rather than medication confounds. Future studies should examine whether this pattern of abnormal neural activity could distinguish bipolar from unipolar depression.
OBJECTIVE: To examine abnormal patterns of frontal cortical-subcortical activity in response to emotional stimuli in euthymic individuals with bipolar disorder type I in order to identify trait-like, pathophysiologic mechanisms of the disorder. We examined potential confounding effects of total psychotropic medication load and illness variables upon neural abnormalities. METHOD: We analyzed neural activity in 19 euthymic bipolar and 24 healthy individuals to mild and intense happy, fearful and neutral faces. RESULTS: Relative to healthy individuals, bipolar subjects had significantly increased left striatal activity in response to mild happy faces (p < 0.05, corrected), decreased right dorsolateral prefrontal cortical (DLPFC) activity in response to neutral, mild and intense happy faces, and decreased left DLPFC activity in response to neutral, mild and intense fearful faces (p < 0.05, corrected). Bipolar and healthy individuals did not differ in amygdala activity in response to either emotion. In bipolar individuals, there was no significant association between medication load and abnormal activity in these regions, but a negative relationship between age of illness onset and amygdala activity in response to mild fearful faces (p = 0.007). Relative to those without comorbidities, bipolar individuals with comorbidities showed a trend increase in left striatal activity in response to mild happy faces. CONCLUSIONS: Abnormally increased striatal activity in response to potentially rewarding stimuli and decreased DLPFC activity in response to other emotionally salient stimuli may underlie mood instabilities in euthymic bipolar individuals, and are more apparent in those with comorbid diagnoses. No relationship between medication load and abnormal neural activity in bipolar individuals suggests that our findings may reflect pathophysiologic mechanisms of the illness rather than medication confounds. Future studies should examine whether this pattern of abnormal neural activity could distinguish bipolar from unipolar depression.
Authors: Kezia Lange; Leanne M Williams; Andrew W Young; Edward T Bullmore; Michael J Brammer; Steven C R Williams; Jeffrey A Gray; Mary L Phillips Journal: Biol Psychiatry Date: 2003-02-01 Impact factor: 13.382
Authors: Hilary P Blumberg; Nelson H Donegan; Charles A Sanislow; Susan Collins; Cheryl Lacadie; Pawel Skudlarski; Ralitza Gueorguieva; Robert K Fulbright; Thomas H McGlashan; John C Gore; John H Krystal Journal: Psychopharmacology (Berl) Date: 2005-10-26 Impact factor: 4.530
Authors: Dennis S Charney; Charles B Nemeroff; Lydia Lewis; Sally K Laden; Jack M Gorman; Eugene M Laska; Michael Borenstein; Charles L Bowden; Arthur Caplan; Graham J Emslie; Dwight L Evans; Barbara Geller; Lenore E Grabowski; Jay Herson; Ned H Kalin; Paul E Keck; Irving Kirsch; K Ranga R Krishnan; David J Kupfer; Robert W Makuch; Franklin G Miller; Herbert Pardes; Robert Post; Mildred M Reynolds; Laura Roberts; Jerrold F Rosenbaum; Donald L Rosenstein; David R Rubinow; A John Rush; Neal D Ryan; Gary S Sachs; Alan F Schatzberg; Susan Solomon Journal: Arch Gen Psychiatry Date: 2002-03
Authors: Hilary P Blumberg; Hoi-Chung Leung; Pawel Skudlarski; Cheryl M Lacadie; Carolyn A Fredericks; Brent C Harris; Dennis S Charney; John C Gore; John H Krystal; Bradley S Peterson Journal: Arch Gen Psychiatry Date: 2003-06
Authors: M T Keener; J C Fournier; B C Mullin; D Kronhaus; S B Perlman; E LaBarbara; J C Almeida; M L Phillips Journal: Psychol Med Date: 2012-01-25 Impact factor: 7.723
Authors: Rebecca Kerestes; Zubin Bhagwagar; Pradeep J Nathan; Shashwath A Meda; Cecile D Ladouceur; Kathleen Maloney; David Matuskey; Barbara Ruf; Aybala Saricicek; Fei Wang; Godfrey D Pearlson; Mary L Phillips; Hilary P Blumberg Journal: Psychiatry Res Date: 2012-05-16 Impact factor: 3.222
Authors: Amy T Peters; Andrew D Peckham; Jonathan P Stange; Louisa G Sylvia; Natasha S Hansen; Stephanie Salcedo; Scott L Rauch; Andrew A Nierenberg; Darin D Dougherty; Thilo Deckersbach Journal: J Psychiatr Res Date: 2014-03-02 Impact factor: 4.791
Authors: Daniel P Dickstein; Brendan A Rich; Roxann Roberson-Nay; Lisa Berghorst; Deborah Vinton; Daniel S Pine; Ellen Leibenluft Journal: Bipolar Disord Date: 2007-11 Impact factor: 6.744
Authors: Kelly A Ryan; Shervin Assari; Kaley Angers; David F Marshall; Kristin Hinrichs; Rebecca Easter; Pallavi Babu; Bethany D Pester; Scott A Langenecker; Melvin G McInnis Journal: Bipolar Disord Date: 2017-09-14 Impact factor: 6.744
Authors: Amy S Garrett; Allan L Reiss; Meghan E Howe; Ryan G Kelley; Manpreet K Singh; Nancy E Adleman; Asya Karchemskiy; Kiki D Chang Journal: J Am Acad Child Adolesc Psychiatry Date: 2012-06-27 Impact factor: 8.829