Hostname: page-component-5b777bbd6c-j65dx Total loading time: 0 Render date: 2025-06-21T19:24:32.276Z Has data issue: false hasContentIssue false
  • English
  • Français

A ventral prefrontal-amygdala neural system in bipolar disorder: a view from neuroimaging research

Published online by Cambridge University Press:  24 June 2014

Fay Y. Womer ,
Jessica H. Kalmar ,
Fei Wang  and
Hilary P. Blumberg
Fay Y. Womer*
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA REAP Depression Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
Jessica H. Kalmar
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA REAP Depression Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
Fei Wang
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA REAP Depression Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
Hilary P. Blumberg
Affiliation:
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA Child Study Center, Yale University School of Medicine, New Haven, CT, USA REAP Depression Center, Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
*
Fay Y. Womer, MD, Mood Disorders Research Program, Department of Psychiatry, Yale University School of Medicine, 300 George Street Suite 901, New Haven, Connecticut, USA. Tel: 203-785-6180; Fax: 203-737-2513; E-mail: fay.womer@yale.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

In the past decade, neuroimaging research has identified key components in the neural system that underlies bipolar disorder (BD). The ventral prefrontal cortex (VPFC) and amygdala are highly interconnected structures that jointly play a central role in emotional regulation. Numerous research groups have reported prominent structural and functional abnormalities within the VPFC and amygdala supporting their essential role in a neural system underlying the emotional dysregulation that is a core feature of BD. Findings in BD also include those in brain regions interconnected with the VPFC and amygdala, including the ventral striatum, hippocampus and the cerebellum. Abnormalities in these regions may contribute to symptoms that reflect disruption in functions sub-served by these structures, including motivational, mnemonic and psychomotor functions.

This article will first review leads from behavioural neurology that implicated these neural system abnormalities in BD. It will then review findings from structural and functional imaging studies to support the presence of abnormalities within these neural system components in BD. It will also review new findings from studies using diffusion tensor imaging (DTI) that provide increasing evidence of abnormalities in the connections between these neural system components in BD. Emerging data supporting differences in this neural system during adolescence, as well as potential beneficial effects of treatment on structure and function will also be presented. Finally, the article will discuss the implications for future investigations, including those for early identification and treatment of BD.

Keywords

adolescentsadultsbipolar disorderDTIfMRIstructural MRI
Type
Review article
Information
Acta Neuropsychiatrica , Volume 21 , Issue 5 , October 2009 , pp. 228 - 238
Copyright
Copyright © 2009 John Wiley & Sons A/S

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Judd, LL, Akiskal, HS, Schettler, PJet al. Psychosocial disability in the course of bipolar I and II disorders:a prospective, comparative, longitudinal study. Arch Gen Psychiatry 2005;62:1322–1330. CrossRefGoogle ScholarPubMed
Goldstein, TR, Birmaher, B, Axelson, Det al. Psychosocial functioning among bipolar youth. J Affect Disord 2009;114:174–183. CrossRefGoogle ScholarPubMed
Huxley, N, Baldessarini, RJ.Disability and its treatment in Bipolar disorder patients. Bipolar Disord 2007;9:183–196. CrossRefGoogle ScholarPubMed
Marangell, LB, Dennehy, EB, Miyahara, S, Wisniewski, SR, Bauer, MS, Rapaport, MH, Allen, MH.The functional impact of subsyndromal depressive symptoms in bipolar disorder:Data from STEP-BD. J Affect Disord 2008;114:58–67. CrossRefGoogle ScholarPubMed
Sajatovic, M.Bipolar disorder: disease burden. Am J Manag Care 2005;11:S80–S84. Google ScholarPubMed
Bechara, A, Damasio, H, Damasio, AR, Lee, GP.Different contributions of the human amygdala and ventromedial prefrontal cortex to decision-making. J Neurosci 1999;19:5473–5481. Google ScholarPubMed
Cummings, JL, Mendez, MF.Secondary mania with focal cerebrovascular lesions. Am J Psychiatry 1984;141:1084–1087. Google ScholarPubMed
Damasio, H, Grabowski, T, Frank, R, Galaburda, AM, Damasio, AR.The return of Phineas Gage: clues about the brain from the skull of a famous patient. Science 1994;264:1102–1105. CrossRefGoogle ScholarPubMed
Jastrowitz, M.Beitrage zur localisation im grosshirn and uber deren praktische verwerthung. Dtsch Med Wochenshr 1888;14:81–83. CrossRefGoogle Scholar
Oppenheim, H.Zur pathologie der grosshirngeschwulste. Arch Psychiatry 1889;21:560–578. CrossRefGoogle Scholar
Rolls, ET, Hornak, J, Wade, D, Mcgrath, J.Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage. J Neurol Neurosurg Psychiatry 1994;57:1518–1524. CrossRefGoogle ScholarPubMed
Sackeim, HA, Greenberg, MS, Weiman, AL, Gur, RC, Hungerbuhler, JP, Geschwind, N.Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence. Arch Neurol 1982;39:210–218. CrossRefGoogle ScholarPubMed
Starkstein, SE, Bryer, JB, Berthier, ML, Cohen, B, Price, TR, Robinson, RG.Depression after stroke: the importance of cerebral hemisphere asymmetries. J Neuropsychiatry Clin Neurosci 1991;3:276–285. Google ScholarPubMed
Wexler, BE.Cerebral laterality and psychiatry: a review of the literature. Am J Psychiatry 1980;137:279–291. Google ScholarPubMed
Flor-Henry, P.Schizophrenic-like reactions and affective psychoses associated with temporal lobe epilepsy: etiological factors. Am J Psychiatry 1969;126:400–404. CrossRefGoogle ScholarPubMed
Bear, DM, Fedio, P.Quantitative analysis of interictal behavior in temporal lobe epilepsy. Arch Neurol 1977;34:454–467. CrossRefGoogle ScholarPubMed
Rolls, ET.The functions of the orbitofrontal cortex. Brain Cogn 2004;55:11–29. CrossRefGoogle ScholarPubMed
Starr, MA.Organic nervous diseases. New York: Lea Brothers & Co., 1903. Google Scholar
Bowley, MP, Drevets, WC, Ongur, D, Price, JL.Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 2002;52:404–412. CrossRefGoogle ScholarPubMed
Kim, S, Webster, MJ.Correlation analysis between genome-wide expression profiles and cytoarchitectural abnormalities in the prefrontal cortex of psychiatric disorders. Mol Psychiatry 2008 [Epub ahead of print]. Google ScholarPubMed
Ongur, D, Drevets, WC, Price, JL.Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A 1998;95:13290–13295. CrossRefGoogle ScholarPubMed
Rajkowska, G.Cell pathology in mood disorders. Semin Clin Neuropsychiatry 2002;7:281–292. CrossRefGoogle ScholarPubMed
Tkachev, D, Mimmack, ML, Ryan, MMet al. Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. Lancet 2003;362:798–805. CrossRefGoogle ScholarPubMed
Uranova, N, Orlovskaya, D, Vikhreva, O, Zimina, I, Kolomeets, N, Vostrikov, V, Rachmanova, V.Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull 2001;55:597–610. CrossRefGoogle ScholarPubMed
Uranova, NA, Vostrikov, VM, Orlovskaya, DD, Rachmanova, VI.Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res 2004;67:269–275. CrossRefGoogle ScholarPubMed
Vostrikov, VM, Uranova, NA, Orlovskaya, DD.Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. Schizophr Res 2007;94:273–280. CrossRefGoogle ScholarPubMed
Amaral, DG, Price, JL.Amygdalo-cortical projections in the monkey (Macaca fascicularis). J Comp Neurol 1984;230:465–496. CrossRefGoogle Scholar
Anand, BK, Malhotra, CL, Singh, B, Dua, S.Cerebellar projections to limbic system. J Neurophysiol 1959;22:451–457. Google ScholarPubMed
Heath, RG, Dempesy, CW, Fontana, CJ, Myers, WA.Cerebellar stimulation: effects on septal region, hippocampus, and amygdala of cats and rats. Biol Psychiatry 1978;13:501–529. Google ScholarPubMed
Morecraft, RJ, Geula, C, Mesulam, MM.Cytoarchitecture and neural afferents of orbitofrontal cortex in the brain of the monkey. J Comp Neurol 1992;323:341–358. CrossRefGoogle ScholarPubMed
Nauta, WJ.The problem of the frontal lobe: a reinterpretation. J Psychiatr Res 1971;8:167–187. CrossRefGoogle ScholarPubMed
Ramnani, N.The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci 2006;7:511–522. CrossRefGoogle ScholarPubMed
Snider, RS, Maiti, A.Cerebellar contributions to the Papez circuit. J Neurosci Res 1976;2:133–146. CrossRefGoogle ScholarPubMed
Cavanagh, JT, Van Beck, M, Muir, W, Blackwood, DH.Case-control study of neurocognitive function in euthymic patients with bipolar disorder: an association with mania. Br J Psychiatry 2002;180:320–326. CrossRefGoogle ScholarPubMed
Deckersbach, T, Savage, CR, Reilly-Harrington, N, Clark, L, Sachs, G, Rauch, SL.Episodic memory impairment in bipolar disorder and obsessive-compulsive disorder: the role of memory strategies. Bipolar Disord 2004;6:233–244. CrossRefGoogle ScholarPubMed
Glahn, DC, Bearden, CE, Caetano, Set al. Declarative memory impairment in pediatric bipolar disorder. Bipolar Disord 2005;7:546–554. CrossRefGoogle ScholarPubMed
Pavuluri, MN, Schenkel, LS, Aryal, S, Harral, EM, Hill, SK, Herbener, ES, Sweeney, JA.Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients. Am J Psychiatry 2006;163:286–293. CrossRefGoogle ScholarPubMed
Wolfe, J, Granholm, E, Butters, N, Saunders, E, Janowsky, D.Verbal memory deficits associated with major affective disorders: a comparison of unipolar and bipolar patients. J Affect Disord 1987;13:83–92. CrossRefGoogle ScholarPubMed
Robbins, TW, Everitt, BJ.Neurobehavioural mechanisms of reward and motivation. Curr Opin Neurobiol 1996;6:228–236. CrossRefGoogle ScholarPubMed
Benedetti, F, Serretti, A, Colombo, C, Barbini, B, Lorenzi, C, Campori, E, Smeraldi, E.Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. Am J Med Genet B Neuropsychiatr Genet 2003;123B:23–26. CrossRefGoogle ScholarPubMed
Mitterauer, B.Clock genes, feedback loops and their possible role in the etiology of bipolar disorders: an integrative model. Med Hypotheses 2000;55:155–159. CrossRefGoogle Scholar
Steeves, TD, King, DP, Zhao, Yet al. Molecular cloning and characterization of the human CLOCK gene: expression in the suprachiasmatic nuclei. Genomics 1999;57:189–200. CrossRefGoogle ScholarPubMed
Drevets, WC, Price, JL, Simpson, JR Jret al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386:824–827. CrossRefGoogle ScholarPubMed
Blumberg, HP, Krystal, JH, Bansal, Ret al. Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study. Biol Psychiatry 2006;59:611–618. CrossRefGoogle ScholarPubMed
Doris, A, Belton, E, Ebmeier, KP, Glabus, MF, Marshall, I.Reduction of cingulate gray matter density in poor outcome bipolar illness. Psychiatry Res 2004;130:153–159. CrossRefGoogle ScholarPubMed
Fornito, A, Malhi, GS, Lagopoulos, Jet al. Anatomical abnormalities of the anterior cingulate and paracingulate cortex in patients with bipolar I disorder. Psychiatry Res 2008;162:123–132. CrossRefGoogle ScholarPubMed
Lopez-Larson, MP, Delbello, MP, Zimmerman, ME, Schwiers, ML, Strakowski, SM.Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry 2002;52:93–100. CrossRefGoogle ScholarPubMed
Lyoo, IK, Kim, MJ, Stoll, ALet al. Frontal lobe gray matter density decreases in bipolar I disorder. Biol Psychiatry 2004;55:648–651. CrossRefGoogle ScholarPubMed
Lyoo, IK, Sung, YH, Dager, SRet al. Regional cerebral cortical thinning in bipolar disorder. Bipolar Disord 2006;8:65–74. CrossRefGoogle ScholarPubMed
Nugent, AC, Milham, MP, Bain, EEet al. Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry. Neuroimage 2006;30:485–497. CrossRefGoogle ScholarPubMed
Adler, CM, Delbello, MP, Jarvis, K, Levine, A, Adams, J, Strakowski, SM.Voxel-based study of structural changes in first-episode patients with bipolar disorder. Biol Psychiatry 2007;61:776–781. CrossRefGoogle ScholarPubMed
Frazier, JA, Breeze, JL, Makris, Net al. Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder. Bipolar Disord 2005;7:555–569. CrossRefGoogle ScholarPubMed
Kalmar, JH, Wang, F, Spencer, Let al. Preliminary evidence for progressive prefrontal abnormalities in adolescents and young adults with bipolar disorder. J Int Neuropsychol Soc 2009;15:476–481. CrossRefGoogle Scholar
Kaur, S, Sassi, RB, Axelson, Det al. Cingulate cortex anatomical abnormalities in children and adolescents with bipolar disorder. Am J Psychiatry 2005;162:1637–1643. CrossRefGoogle ScholarPubMed
Najt, P, Nicoletti, M, Chen, HHet al. Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder. Neurosci Lett 2007;413:183–186. CrossRefGoogle ScholarPubMed
Wilke, M, Kowatch, RA, Delbello, MP, Mills, NP, Holland, SK.Voxel-based morphometry in adolescents with bipolar disorder: first results. Psychiatry Res 2004;131:57–69. CrossRefGoogle ScholarPubMed
Dickstein, DP, Milham, MP, Nugent, AC, Drevets, WC, Charney, DS, Pine, DS, Leibenluft, E.Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. Arch Gen Psychiatry 2005;62:734–741. CrossRefGoogle ScholarPubMed
Sanches, M, Sassi, RB, Axelson, Det al. Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study. Psychiatry Res 2005;138:43–49. CrossRefGoogle ScholarPubMed
Blumberg, HP, Kaufman, J, Martin, A, Charney, DS, Krystal, JH, Peterson, BS.Significance of adolescent neurodevelopment for the neural circuitry of bipolar disorder. Ann N Y Acad Sci 2004;1021:376–383. CrossRefGoogle ScholarPubMed
Manji, HK, Moore, GJ, Chen, G.Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry 2000;48:740–754. CrossRefGoogle ScholarPubMed
Moore, GJ, Bebchuk, JM, Wilds, IB, Chen, G, Manji, HK.Lithium-induced increase in human brain grey matter. Lancet 2000;356:1241–1242. CrossRefGoogle ScholarPubMed
Drevets, WC.Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol 2001;11:240–249. CrossRefGoogle ScholarPubMed
Sassi, RB, Nicoletti, M, Brambilla, Pet al. Increased gray matter volume in lithium-treated bipolar disorder patients. Neurosci Lett 2002;329:243–245. CrossRefGoogle ScholarPubMed
Monkul, ES, Matsuo, K, Nicoletti, MAet al. Prefrontal gray matter increases in healthy individuals after lithium treatment: a voxel-based morphometry study. Neurosci Lett 2007;429:7–11. CrossRefGoogle ScholarPubMed
Bearden, CE, Thompson, PM, Dalwani, Met al. Greater cortical gray matter density in lithium-treated patients with bipolar disorder. Biol Psychiatry 2007;62:7–16. CrossRefGoogle ScholarPubMed
Altshuler, LL, Bartzokis, G, Grieder, T, Curran, J, Mintz, J.Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry 1998;55:663–664. Google ScholarPubMed
Blumberg, HP, Kaufman, J, Martin, Aet al. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry 2003;60:1201–1208. CrossRefGoogle ScholarPubMed
Pearlson, GD, Barta, PE, Powers, REet al. Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry 1997;41:1–14. CrossRefGoogle ScholarPubMed
Strakowski, SM, Delbello, MP, Sax, KW, Zimmerman, ME, Shear, PK, Hawkins, JM, Larson, ER.Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999;56:254–260. CrossRefGoogle ScholarPubMed
Scherk, H, Gruber, O, Menzel, Pet al. 5-HTTLPR genotype influences amygdala volume. Eur Arch Psychiatry Clin Neurosci 2009;259:212–217. CrossRefGoogle ScholarPubMed
Chang, K, Karchemskiy, A, Barnea-Goraly, N, Garrett, A, Simeonova, DI, Reiss, A.Reduced amygdalar gray matter volume in familial pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005;44:565–573. CrossRefGoogle ScholarPubMed
Chen, BK, Sassi, R, Axelson, Det al. Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder. Biol Psychiatry 2004;56:399–405. CrossRefGoogle Scholar
Delbello, MP, Zimmerman, ME, Mills, NP, Getz, GE, Strakowski, SM.Magnetic resonance imaging analysis of amygdala and other subcortical brain regions in adolescents with bipolar disorder. Bipolar Disord 2004;6:43–52. CrossRefGoogle ScholarPubMed
Foland, LC, Altshuler, LL, Sugar, CAet al. Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium. Neuroreport 2008;19:221–224. CrossRefGoogle ScholarPubMed
Bearden, CE, Soares, JC, Klunder, ADet al. Three-dimensional mapping of hippocampal anatomy in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2008;47:515–525. CrossRefGoogle ScholarPubMed
Frazier, JA, Chiu, S, Breeze, JLet al. Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. Am J Psychiatry 2005;162:1256–1265. CrossRefGoogle ScholarPubMed
Altshuler, LL, Bartzokis, G, Grieder, Tet al. An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry 2000;48:147–162. CrossRefGoogle ScholarPubMed
Hauser, P, Matochik, J, Altshuler, LL, Denicoff, KD, Conrad, A, Li, X, Post, RM.MRI-based measurements of temporal lobe and ventricular structures in patients with bipolar I and bipolar II disorders. J Affect Disord 2000;60:25–32. CrossRefGoogle ScholarPubMed
Hirayasu, Y, Shenton, ME, Salisbury, DFet al. Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects. Am J Psychiatry 1998;155:1384–1391. CrossRefGoogle ScholarPubMed
Noga, JT, Vladar, K, Torrey, EF.A volumetric magnetic resonance imaging study of monozygotic twins discordant for bipolar disorder. Psychiatry Res 2001;106:25–34. CrossRefGoogle ScholarPubMed
Swayze, VW II, Andreasen, NC, Alliger, RJ, Yuh, WT, Ehrhardt, JC.Subcortical and temporal structures in affective disorder and schizophrenia: a magnetic resonance imaging study. Biol Psychiatry 1992;31:221–240. CrossRefGoogle ScholarPubMed
Velakoulis, D, Pantelis, C, Mcgorry, PDet al. Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study. Arch Gen Psychiatry 1999;56:133–141. CrossRefGoogle ScholarPubMed
Chepenik, LG, Fredericks, C, Papademetris, Xet al. Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder. Neuropsychopharmacology 2009;34:944–951. CrossRefGoogle ScholarPubMed
Mcintosh, AM, Moorhead, TW, Mckirdy, Jet al. Temporal grey matter reductions in bipolar disorder are associated with the BDNF Val66Met polymorphism. Mol Psychiatry 2007;12:902–903. CrossRefGoogle ScholarPubMed
Hwang, J, Lyoo, IK, Dager, SRet al. Basal ganglia shape alterations in bipolar disorder. Am J Psychiatry 2006;163:276–285. CrossRefGoogle ScholarPubMed
Strakowski, SM, Adler, CM, Delbello, MP.Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder? Bipolar Disord 2002;4:80–88. CrossRefGoogle ScholarPubMed
Delbello, MP, Strakowski, SM, Zimmerman, ME, Hawkins, JM, Sax, KW.MRI analysis of the cerebellum in bipolar disorder: a pilot study. Neuropsychopharmacology 1999;21:63–68. CrossRefGoogle ScholarPubMed
Mills, NP, Delbello, MP, Adler, CM, Strakowski, SM.MRI analysis of cerebellar vermal abnormalities in bipolar disorder. Am J Psychiatry 2005;162:1530–1532. CrossRefGoogle ScholarPubMed
Monkul, ES, Hatch, JP, Sassi, RBet al. MRI study of the cerebellum in young bipolar patients. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:613–619. CrossRefGoogle ScholarPubMed
Brambilla, P, Harenski, K, Nicoletti, Met al. MRI study of posterior fossa structures and brain ventricles in bipolar patients. J Psychiatr Res 2001;35:313–322. CrossRefGoogle ScholarPubMed
Altshuler, LL, Bookheimer, SY, Townsend, Jet al. Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study. Biol Psychiatry 2005;58:763–769. CrossRefGoogle ScholarPubMed
Blumberg, HP, Leung, HC, Skudlarski, Pet 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. CrossRefGoogle ScholarPubMed
Blumberg, HP, Stern, E, Ricketts, Set al. Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. Am J Psychiatry 1999;156:1986–1988. Google ScholarPubMed
Elliott, R, Ogilvie, A, Rubinsztein, JS, Calderon, G, Dolan, RJ, Sahakian, BJ.Abnormal ventral frontal response during performance of an affective go/no go task in patients with mania. Biol Psychiatry 2004;55:1163–1170. CrossRefGoogle ScholarPubMed
Rubinsztein, JS, Fletcher, PC, Rogers, RDet al. Decision-making in mania: a PET study. Brain 2001;124:2550–2563. CrossRefGoogle ScholarPubMed
Chen, CH, Lennox, B, Jacob, Ret 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. CrossRefGoogle ScholarPubMed
Lawrence, NS, Williams, AM, Surguladze, Set 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. CrossRefGoogle ScholarPubMed
Blumberg, HP, Donegan, NH, Sanislow, CAet al. Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder. Psychopharmacology (Berl) 2005;183:308–313. CrossRefGoogle ScholarPubMed
Kronhaus, DM, Lawrence, NS, Williams, AMet al. Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortex. Bipolar Disord 2006;8:28–39. CrossRefGoogle ScholarPubMed
Kruger, S, Seminowicz, D, Goldapple, K, Kennedy, SH, Mayberg, HS.State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge. Biol Psychiatry 2003;54:1274–1283. CrossRefGoogle ScholarPubMed
Kruger, S, Alda, M, Young, LT, Goldapple, K, Parikh, S, Mayberg, HS.Risk and resilience markers in bipolar disorder: brain responses to emotional challenge in bipolar patients and their healthy siblings. Am J Psychiatry 2006;163:257–264. CrossRefGoogle ScholarPubMed
Malhi, GS, Lagopoulos, J, Sachdev, PS, Ivanovski, B, Shnier, R.An emotional Stroop functional MRI study of euthymic bipolar disorder. Bipolar Disord 2005;7(Suppl. 5): 58–69. CrossRefGoogle ScholarPubMed
Blumberg, HP, Martin, A, Kaufman, Jet al. Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. Am J Psychiatry 2003;160:1345–1347. CrossRefGoogle ScholarPubMed
Leibenluft, E, Rich, BA, Vinton, DTet al. Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder. Am J Psychiatry 2007;164:52–60. CrossRefGoogle ScholarPubMed
Pavuluri, MN, O’connor, MM, Harral, E, Sweeney, JA.Affective neural circuitry during facial emotion processing in pediatric bipolar disorder. Biol Psychiatry 2007;62:158–167. CrossRefGoogle ScholarPubMed
Rich, BA, Vinton, DT, Roberson-Nay, Ret al. Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder. Proc Natl Acad Sci U S A 2006;103:8900–8905. CrossRefGoogle ScholarPubMed
Jogia, J, Haldane, M, Cobb, A, Kumari, V, Frangou, S.Pilot investigation of the changes in cortical activation during facial affect recognition with lamotrigine monotherapy in bipolar disorder. Br J Psychiatry 2008;192:197–201. CrossRefGoogle ScholarPubMed
Shah, MP, Wang, F, Kalmar, JHet al. Role of variation in the Serotonin Transporter Protein Gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder. Neuropsychopharmacology 2009;34:1301–1305. CrossRefGoogle ScholarPubMed
Altshuler, L, Bookheimer, S, Proenza, MAet al. Increased amygdala activation during mania: a functional magnetic resonance imaging study. Am J Psychiatry 2005;162:1211–1213. CrossRefGoogle ScholarPubMed
Chang, KD, Wagner, C, Garrett, A, Howe, M, Reiss, A.A preliminary functional magnetic resonance imaging study of prefrontal-amygdalar activation changes in adolescents with bipolar depression treated with lamotrigine. Bipolar Disord 2008;10:426–431. CrossRefGoogle ScholarPubMed
Drevets, WC, Price, JL, Bardgett, ME, Reich, T, Todd, RD, Raichle, ME.Glucose metabolism in the amygdala in depression: relationship to diagnostic subtype and plasma cortisol levels. Pharmacol Biochem Behav 2002;71:431–447. CrossRefGoogle ScholarPubMed
Ketter, TA, Kimbrell, TA, George, MSet al. Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder. Biol Psychiatry 2001;49:97–109. CrossRefGoogle ScholarPubMed
Mah, L, Zarate, CA Jr, Singh, J, Duan, YF, Luckenbaugh, DA, Manji, HK, Drevets, WC.Regional cerebral glucose metabolic abnormalities in bipolar II depression. Biol Psychiatry 2007;61:765–775. CrossRefGoogle ScholarPubMed
Malhi, GS, Lagopoulos, J, Ward, PBet al. Cognitive generation of affect in bipolar depression: an fMRI study. Eur J Neurosci 2004;19:741–754. CrossRefGoogle Scholar
Yurgelun-Todd, DA, Gruber, SA, Kanayama, G, Killgore, WD, Baird, AA, Young, AD.fMRI during affect discrimination in bipolar affective disorder. Bipolar Disord 2000;2:237–248. CrossRefGoogle ScholarPubMed
Krystal, JH, Sanacora, G, Blumberg, Het al. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry 2002;7(Suppl. 1): S71–S80. CrossRefGoogle ScholarPubMed
Braga, MF, Aroniadou-Anderjaska, V, Post, RM, Li, H.Lamotrigine reduces spontaneous and evoked GABAA receptor-mediated synaptic transmission in the basolateral amygdala: implications for its effects in seizure and affective disorders. Neuropharmacology 2002;42:522–529. CrossRefGoogle ScholarPubMed
Tian, LM, Alkadhi, KA.Valproic acid inhibits the depolarizing rectification in neurons of rat amygdala. Neuropharmacology 1994;33:1131–1138. CrossRefGoogle ScholarPubMed
Blumberg, HP, Stern, E, Martinez, Det al. Increased anterior cingulate and caudate activity in bipolar mania. Biol Psychiatry 2000;48:1045–1052. CrossRefGoogle ScholarPubMed
Caligiuri, MP, Brown, GG, Meloy, MJet al. An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder. Psychiatry Res 2003;123:171–182. CrossRefGoogle ScholarPubMed
Malhi, GS, Lagopoulos, J, Sachdev, P, Mitchell, PB, Ivanovski, B, Parker, GB.Cognitive generation of affect in hypomania: an fMRI study. Bipolar Disord 2004;6:271–285. CrossRefGoogle Scholar
Goodwin, GM, Cavanagh, JT, Glabus, MF, Kehoe, RF, O'carroll, RE, Ebmeier, KP.Uptake of 99mTc-exametazime shown by single photon emission computed tomography before and after lithium withdrawal in bipolar patients: associations with mania. Br J Psychiatry 1997;170:426–430. CrossRefGoogle ScholarPubMed
Malhi, GS, Lagopoulos, J, Owen, AM, Ivanovski, B, Shnier, R, Sachdev, P.Reduced activation to implicit affect induction in euthymic bipolar patients: an fMRI study. J Affect Disord 2007;97:109–122. CrossRefGoogle Scholar
Strakowski, SM, Adler, CM, Holland, SK, Mills, NP, Delbello, MP, Eliassen, JC.Abnormal FMRI brain activation in euthymic bipolar disorder patients during a counting Stroop interference task. Am J Psychiatry 2005;162:1697–1705. CrossRefGoogle ScholarPubMed
Loeber, RT, Gruber, SA, Cohen, BM, Renshaw, PF, Sherwood, AR, Yurgelun-Todd, DA.Cerebellar blood volume in bipolar patients correlates with medication. Biol Psychiatry 2002;51:370–376. CrossRefGoogle ScholarPubMed
Atmaca, M, Ozdemir, H, Yildirim, H.Corpus callosum areas in first-episode patients with bipolar disorder. Psychol Med 2007;37:699–704. CrossRefGoogle ScholarPubMed
Coffman, JA, Bornstein, RA, Olson, SC, Schwarzkopf, SB, Nasrallah, HA.Cognitive impairment and cerebral structure by MRI in bipolar disorder. Biol Psychiatry 1990;27:1188–1196. CrossRefGoogle ScholarPubMed
Haznedar, MM, Roversi, F, Pallanti, Set al. Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses. Biol Psychiatry 2005;57:733–742. CrossRefGoogle ScholarPubMed
Brambilla, P, Nicoletti, MA, Sassi, RBet al. Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder. Biol Psychiatry 2003;54:1294–1297. CrossRefGoogle ScholarPubMed
Brambilla, P, Nicoletti, M, Sassi, RB, Mallinger, AG, Frank, E, Keshavan, MS, Soares, JC.Corpus callosum signal intensity in patients with bipolar and unipolar disorder. J Neurol Neurosurg Psychiatry 2004;75:221–225. Google ScholarPubMed
Caetano, SC, Silveira, CM, Kaur, Set al. Abnormal corpus callosum myelination in pediatric bipolar patients. J Affect Disord 2008;108:297–301. CrossRefGoogle ScholarPubMed
Schmahmann, JD, Pandya, DN.Fiber pathways of the brain. New York: Oxford University Press, 2006. CrossRefGoogle Scholar
Beaulieu, C.The basis of anisotropic water diffusion in the nervous system–a technical review. NMR Biomed 2002;15:435–455. CrossRefGoogle ScholarPubMed
Adler, CM, Holland, SK, Schmithorst, V, Wilke, M, Weiss, KL, Pan, H, Strakowski, SM.Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study. Bipolar Disord 2004;6:197–203. CrossRefGoogle ScholarPubMed
Adler, CM, Adams, J, Delbello, MPet al. Evidence of white matter pathology in bipolar disorder adolescents experiencing their first episode of mania: a diffusion tensor imaging study. Am J Psychiatry 2006;163:322–324. CrossRefGoogle ScholarPubMed
Beyer, JL, Taylor, WD, Macfall, JRet al. Cortical white matter microstructural abnormalities in bipolar disorder. Neuropsychopharmacology 2005;30:2225–2229. CrossRefGoogle ScholarPubMed
Bruno, S, Cercignani, M, Ron, MA.White matter abnormalities in bipolar disorder: a voxel-based diffusion tensor imaging study. Bipolar Disord 2008;10:460–468. CrossRefGoogle ScholarPubMed
Houenou, J, Wessa, M, Douaud, Get al. Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex. Mol Psychiatry 2007;12:1001–1010. CrossRefGoogle ScholarPubMed
Regenold, WT, D’agostino, CA, Ramesh, N, Hasnain, M, Roys, S, Gullapalli, RP.Diffusion-weighted magnetic resonance imaging of white matter in bipolar disorder: a pilot study. Bipolar Disord 2006;8:188–195. CrossRefGoogle ScholarPubMed
Versace, A, Almeida, JR, Hassel, Set al. Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics. Arch Gen Psychiatry 2008;65:1041–1052. CrossRefGoogle ScholarPubMed
Wang, F, Kalmar, JH, Edmiston, Eet al. Abnormal corpus callosum integrity in bipolar disorder: a diffusion tensor imaging study. Biol Psychiatry 2008;64:730–733. CrossRefGoogle ScholarPubMed
Wang, F, Jackowski, M, Kalmar, JHet al. Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging. Br J Psychiatry 2008;193:126–129. CrossRefGoogle ScholarPubMed
Kalmar, JH, Wang, F, Chepenik, LGet al. Relation between amygdala structure and function in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2009;48:636–642. CrossRefGoogle ScholarPubMed
Wang, F, Kalmar, JH, He, Yet al. Functional and structural connectivity between the perigenual anterior cingulate and amygdala in bipolar disorder. Biol Psychiatry 2009;66:516–521. CrossRefGoogle ScholarPubMed