Abstract
Bipolar I disorder (BPI) is among the top 10 most debilitating illnesses globally. In this critical review, we first review recent functional neuroimaging findings in two core domains of pathology in BPI: emotion processing and executive control. These abnormalities in core domains represent potential endophenotypes of the illness. We then show that an emerging number of studies have demonstrated that neuroimaging can help to identify endophenotypic markers whose identification would help to clarify diagnosis and discriminate the depression in BPI from that of unipolar depression and identify at-risk individuals who will subsequently develop the illness (to facilitate early intervention). We end by reviewing the new directions in neuroimaging in BPI, including studies of children with bipolar disorder, potential medication effects, and the use of newer neuroimaging techniques to help us achieve the previously mentioned goals of improving BPI patients’ mental well-being.
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References and Recommended Reading
Baldessarini RJ, Tondo L: Suicide risk and treatments for patients with bipolar disorder. JAMA 2003, 290:1517–1519.
Merikangas KR, Akiskal HS, Angst J, et al.: Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2007, 64:543–552.
Hirschfeld RM, Lewis L, Vornik LA: Perceptions and impact of bipolar disorder: how far have we really come? Results of the National Depressive and Manic-depressive Association 2000 survey of individuals with bipolar disorder. J Clin Psychiatry 2003, 64:161–174.
Fagiolini A, Frank E, Cherry CR, et al.: Clinical indicators for the use of antidepressants in the treatment of bipolar I depression. Bipolar Disord 2002, 5:277–282.
Gottesman II, Gould TD: The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003, 160:636–645.
Phillips ML, Frank E: Redefining bipolar disorder-toward DSM-V. Am J Psychiatry 2006, 163:1135–1136.
Stuss DT, Levine B: Adult clinical neuropsychology: lessons from studies of the frontal lobes. Annu Rev Psychol 2000, 53:401–433.
Phillips ML, Drevets WC, Rauch SL, Lane R: Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol Psychiatry 2003, 54:515–528.
Phillips ML, Vieta E: Identifying functional neuroimaging biomarkers of bipolar disorder: toward DSM-V. Schizophr Bull 2007, 33:893–904.
Phillips ML, Drevets WC, Rauch SL, et al.: Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry 2003, 54:504–514.
Robbins TW: Dissociating executive functions of the prefrontal cortex. In The Prefrontal Cortex: Executive and Cognitive Functions. Edited by Roberts AC, Robbins TW, Weiskrantz LR. New York: Oxford University Press; 1998.
Zola-Morgan S, Squire LR, Alvarez-Royo P, et al.: Independence of memory functions and emotional behavior: separate contributions of the hippocampal formation and the amygdale. Hippocampus 1991, 1:207–220.
Ekman P: Facial expression of emotion: an old controversy and new findings. Philos Trans R Soc London B Biol Sci 1992, 335:63–69.
Lawrence NS, Williams AM, Surguladze S, et al.: Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression, Biol Psychiatry 2004, 55:578–587.
Yurgelun-Todd DA, Gruber SA, Kanayama G, et al.: fMRI during affect discrimination in bipolar affective disorder. Bipolar Disord 2000, 2:237–248.
Blumberg HP, Donegan NH, Sanislow CA, et al.: Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder. Psychopharmacology 2005, 183:308–313.
Wessa M, Houenou J, Paillere-Martinot ML, et al.: Fronto-striatal overactivation in euthymic bipolar patients during an emotional go/nogo task. Am J Psychiatry 2007, 164:638–646.
Malhi GS, Lagopoulos J, Sachdev PS, et al.: An emotional Stroop functional MRI study of euthymic bipolar disorder. Bipolar Disord 2005, 7:58–69.
Blumberg HP, Leung HC, Skudlarski P, et al.: A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Arch Gen Psychiatry 2003, 60:601–609.
Chen CH, Lennox B, Jacob R, et al.: Explicit and implicit facial affect recognition in manic and depressed states of bipolar disorder: a functional magnetic resonance imaging study. Biol Psychiatry 2006, 59:31–39.
Altshuler L, Bookheimer S, Proenza MA, et al.: Increased amygdala activation during mania: a functional magnetic resonance imaging study. Am J Psychiatry 2005, 162:1211–1213.
Lennox BR, Calder JR, Lupson J, et al.: Behavioral and neurocognitive responses to sad facial affect are attenuated in patients with mania. Psychol Med 2004, 34:795–802.
Malhi GS, Lagopoulos J, Ward PB, et al.: Cognitive generation of affect in bipolar depression: an fMRI study. Eur J Neurosci 2004, 19:741–754.
Drevets WC, Raichle ME: Reciprocal suppression of regional cerebral blood flow during emotional versus higher cognitive processes: implications for interaction between emotion and cognition. Cogn Emot 1998, 12:353–385.
Häger F, Volz HP, Gaser C, et al.: Challenging the anterior attentional system with a continuous performance task: a functional magnetic resonance imaging approach. Eur Arch Psychiatry Clin Neurosci 1998, 248:161–170.
Strakowski SM, Adler CM, Holland SK, et al.: Abnormal FMRI brain activation in euthymic bipolar disorder patients during a counting Stroop interference task. Am J Psychiatry 2005, 162:1697–1705.
Monks PJ, Thompson JM, Bullmore ET, et al.: A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction. Bipolar Disord 2004, 6:550–564.
Gruber SA, Rogowska J, Yurgelun-Todd DA: Decreased activation of the anterior cingulate in bipolar patients: an fMRI study. J Affect Disord 2004, 82:191–201.
Adler CM, Holland SK, Schmithorst V, et al.: Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task. Bipolar Disord 2004, 6:540–549.
Marchand WR, Lee JN, Thatcher GW, et al.: A functional MRI study of a paced motor activation task to evaluate frontal-subcortical circuit function in bipolar depression. Psychiatry Res 2007, 155:221–230.
Kronhaus DM, Lawrence NS, Williams AM, et al.: Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortex. Bipolar Disord 2006, 8:28–39.
Drevets WC, Price JL, Bardgett ME, et al.: Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels. Pharmacol Biochem Behav 2002, 71:431–447.
Mah L, Zarate CA, Jr, Singh J, et al.: Regional cerebral glucose metabolic abnormalities in bipolar II depression. Biol Psychiatry 2007, 61:765–775.
Blumberg HP, Stern E, Martinez D, et al.: Increased anterior cingulate and caudate activity in bipolar mania. Biol Psychiatry 2000, 48:1045–1052.
Kruger S, Seminowicz D, Goldapple K, et al.: State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge. Biol Psychiatry 2003, 54:1274–1283.
Rubinsztein JS, Fletcher PC, Rogers RD, et al.: Decision making in mania: a PET study. Brain 2001, 124:2550–2563.
Ketter TA, Kimbrell Ta, George MS, et al.: Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder. Biol Psychiatry 2001, 49:97–109.
Brooks JO 3rd, Wang PW, Strong C, et al.: Preliminary evidence of differential relations between prefrontal cortex metabolism and sustained attention in depressed adults with bipolar disorder and healthy controls. Bipolar Disord 2006, 3:248–254.
Altshuler LL, Bartzokis G, Grieder T, et al.: An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry 2000, 48:147–162.
Lopez-Larson MP, DelBello MP, Zimmerman ME, et al.: Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry 2002, 52:93–100.
Blumberg HP, Kaufman J, Martin A, et al.: Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry 2003, 60:1201–1208.
Mayberg HS, Brannan SK, Tekell JL, et al.: Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 2000, 48:830–843.
Martin SD, Martin E, Rai SS, et al.: Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings. Arch Gen Psychiatry 2001, 58:641–648.
Fu CH, Williams SC, Cleare AJ, et al.: Attenuation of the neural response to sad faces in major depression by antide-pressant treatment: a prospective, event-related functional magnetic resonance imaging study. Arch Gen Psychiatry 2004, 61:877–889.
Surguladze S, Bramer MJ, Keedwell P, et al.: A differential pattern of neural response toward sad versus happy facial expressions in UPD. Biol Psychiatry 2005, 57:201–209.
Elliott R, Baker SC, Rogers RD, et al.: Prefrontal dysfunction in depressed patients performing a complex planning task: a study using positron emission tomography. Psychol Med 1997, 27:931–942.
Siegle GJ, Steinhauer SR, Thase ME, et al.: Can’t shake that feeling: fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biol Psychiatry 2002, 51:693–707.
Sheline YI, Barch DM, Donnelly JM, et al.: Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biol Psychiatry 2001, 50:651–658.
Rich BA, Schmajuk M, Perez-Edgar KE, et al.: The impact of reward, punishment, and frustration on attention in pediatric bipolar disorder. Biol Psychiatry 2005, 58: 532–539.
Birmaher B, Axelson D, Strober M, et al.: Clinical course of children and adolescents with bipolar spectrum disorders. Arch Gen Psychiatry 2006, 63:175–183.
Blumberg HP, Martin A, Kaufman J, et al.: Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. Am J Psychiatry 2003, 7:1345–1347.
Chang K, Adleman NE, Dienes K, et al.: Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation. Arch Gen Psychiatry 2004, 61:781–792.
McClure EB, Treland JE, Snow J, et al.: Deficits in social cognition and response flexibility in pediatric bipolar disorder. Am J Psychiatry 2005, 162:1644–1651.
Dickstein DP, Milham MP, Nugent AC, et al.: Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. Arch Gen Psychiatry 2005, 62:734–741.
Blumberg HP, Fredericks C, Wang F, et al.: Preliminary evidence for persistent abnormalities in amygdala volumes in adolescents and young adults with bipolar disorder. Bipolar Disord 2005, 7:570–576.
Chen BK, Sassi R, Axelson D, et al.: Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder. Biol Psychiatry 2004, 56:399–405.
Blumberg HP, Krystal JH, Bansal R, et al.: Age, rapidcycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study. Biol Psychiatry 2006, 59:611–618.
Streit M, Dammers J, Simsek-Kraues S, et al.: Time course of regional brain activations during facial emotion recognition in humans. Neurosci Lett 2003, 342:101–104.
Tollkötter M, Pfleiderer B, Soros P, Michael N: Effects of antidepressive therapy on auditory processing in severely depressed patients: a combined MRS and MEG study. J Psychiatr Res 2006, 40:293–306.
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Keener, M.T., Phillips, M.L. Neuroimaging in bipolar disorder: A critical review of current findings. Curr Psychiatry Rep 9, 512–520 (2007). https://doi.org/10.1007/s11920-007-0070-2
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DOI: https://doi.org/10.1007/s11920-007-0070-2