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The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings

Abstract

The authors review existing structural and functional neuroimaging studies of patients with bipolar disorder and discuss how these investigations enhance our understanding of the neurophysiology of this illness. Findings from structural magnetic resonance imaging (MRI) studies suggest that some abnormalities, such as those in prefrontal cortical areas (SGPFC), striatum and amygdala exist early in the course of illness and, therefore, potentially, predate illness onset. In contrast, other abnormalities, such as those found in the cerebellar vermis, lateral ventricles and other prefrontal regions (eg, left inferior), appear to develop with repeated affective episodes, and may represent the effects of illness progression and associated factors. Magnetic resonance spectroscopy investigations have revealed abnormalities of membrane and second messenger metabolism, as well as bioenergetics, in striatum and prefrontal cortex. Functional imaging studies report activation differences between bipolar and healthy controls in these same anterior limibic regions. Together, these studies support a model of bipolar disorder that involves dysfunction within subcortical (striatal–thalamic)–prefrontal networks and the associated limbic modulating regions (amygdala, midline cerebellum). These studies suggest that, in bipolar disorder, there may be diminished prefrontal modulation of subcortical and medial temporal structures within the anterior limbic network (eg, amygdala, anterior striatum and thalamus) that results in dysregulation of mood. Future prospective and longitudinal studies focusing on these specific relationships are necessary to clarify the functional neuroanatomy of bipolar disorder.

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References

  1. Narrow WE, Rae DS, Robins LN, Regier DA . Revised prevalence estimates of mental disorders in the United States: using a clinical significance criterion to reconcile 2 surveys’ estimates. Arch Gen Psychiatry 2002; 59: 115–123.

    PubMed  Article  Google Scholar 

  2. Angst J . The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998; 50: 143–151.

    CAS  PubMed  Article  Google Scholar 

  3. Murray CJL, Lopez AD . The Global Burden of Disease: Summary, Harvard School of Public Health Monograph, Cambridge, MA 1996.

  4. Strakowski SM, DelBello MP, Adler C, Cecil KM, Sax KW . Neuroimaging in bipolar disorder. Bipolar Disord 2000; 2: 148–164.

    CAS  Article  PubMed  Google Scholar 

  5. Strakowski SM . Differential brain mechanisms in bipolar and unipolar disorders: considerations from brain imaging. In: JC Soares (ed). Brain Imaging in Affective Disorders. Marcel Dekker, Inc.: NY, 2002.

    Google Scholar 

  6. Strakowski SM, Adler C, DelBello MP . Comparison of morphometric magnetic resonance imaging findings in bipolar disorder and unipolar depression. Bipolar Disord 2002; 4: 80–88.

    PubMed  Article  Google Scholar 

  7. Hoge EA, Friedman L, Schultz SC . Meta-analysis of brain size in bipolar disorder. Schiozphr Res 1999; 37: 177–181.

    CAS  Article  Google Scholar 

  8. Sax KW, Strakowski SM, Zimmerman ME, DelBello MP, Keck Jr PE, Hawkins JM . Frontosubcortical neuroanatomy and the Continuous Performance Test in mania. Am J Psychiatry 1999; 156: 139–141.

    CAS  Article  PubMed  Google Scholar 

  9. 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.

    PubMed  Article  Google Scholar 

  10. Brambilla P, Harenski K, Nicoletti M, Mallinger AG, Frank E, Kupfer DJ et al. Differential effects of age on brain gray matter in bipolar patients and healthy individuals. Neuropsychobiology 2001; 43: 242–247.

    CAS  Article  PubMed  Google Scholar 

  11. Drevets WC, Price JL, Simpson Jr JR, Todd RD, Reich T, Vannier M et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997; 386: 824–827.

    CAS  PubMed  Article  Google Scholar 

  12. Hirayasu Y, Shenton ME, Salisbury DF, Kwon JS, Wible CG, Fischer IA et al. Subgenual cingulate cortex volume in first-episode psychosis. Am J Psychiatry 1999; 156: 1091–1093.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Brambilla P, Nicoletti MA, Harenski K, Sassi RB, Mallinger AG, Franke E et al. Anatomical MRI study of subgenual prefrontal cortex in bipolar and unipolar subjects. Neuropsychopharmacology 2002; 27: 792–799.

    Article  PubMed  Google Scholar 

  14. Rajkowska G, Halaris A, Selemon LD . Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 2000; 49: 741–752.

    Article  Google Scholar 

  15. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY et al. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999; 45: 1085–1098.

    CAS  PubMed  Google Scholar 

  16. Öngür D, Drevets WC, Price JL . Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998; 95: 13290–13295.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Aylward EH, Roberts-Twillie JV, Barta PE, Kumar AJ, Harris GJ, Geer M et al. Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder. Am J Psychiatry 1994; 151: 687–693.

    CAS  PubMed  Article  Google Scholar 

  18. Strakowski SM, DelBello MP, Sax KW, Zimmerman ME, Shear PK, Hawkins JM et al. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999; 56: 254–260.

    CAS  Article  PubMed  Google Scholar 

  19. Strakowski SM, DelBello MP, Zimmerman ME, Getz GE, Mills NP, Ret J et al. Ventricular and periventricular structural volumes in first- vs multiple-episode bipolar disorder. Am J Psychiatry 2002; 159: 1841–1847.

    PubMed  Article  Google Scholar 

  20. 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.

    CAS  PubMed  Article  Google Scholar 

  21. Brambilla P, Harenski K, Nicoletti MA, Mallinger AG, Frank E, Kupfer DJ et al. Anatomical MRI study of basal ganglia in bipolar disorder patients. Psychiatry Res. Neuroimaging 2001; 106: 65–80.

    CAS  PubMed  Article  Google Scholar 

  22. 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.

    PubMed  Article  Google Scholar 

  23. Dupont RM, Butters N, Schafer K, Wilson T, Hesselink J, Gillin JC . Diagnostic specificity of focal white matter abnormalities in bipolar and unipolar mood disorder. Biol Psychiatry 1995; 38: 482–486.

    CAS  PubMed  Article  Google Scholar 

  24. Caetano SC, Sassi R, Brambilla P, Harenski K, Nicoletti M, Mallinger AG et al. MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals. Psychiatry Res: Neuroimaging 2001; 108: 161–168.

    CAS  PubMed  Article  Google Scholar 

  25. Swayze II VW, 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.

    Article  PubMed  Google Scholar 

  26. Pearlson GD, Barta PE, Powers RE, Menon RR, Richards SS, Aylward EH, et al., Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia vs bipolar disorder. Biol Psychiatry 1997; 41: 1–14.

    CAS  PubMed  Article  Google Scholar 

  27. Altshuler LL, Bartzokis G, Grieder T, Curran J, Jimenez T, Leight K et al. An MRI study of temporal lobe structures in men with bipolar disorder and schizophrenia. Biol Psychiatry 2000; 48: 147–162.

    CAS  Article  PubMed  Google Scholar 

  28. Brambilla P, Harenski K, Nicoletti M, Sassi RB, Mallinger AG, Frank E et al. MRI investigation of temporal lobe structures in bipolar patients. J Psychiatr Res 2003; 37: 287–295.

    PubMed  Article  Google Scholar 

  29. McCarley RW, Wible CG, Frumin M, Hirayasu Y, Lefitt JJ, Fischer IA et al. MRI anatomy of schizophrenia. Biol Psychiatry 1999; 45: 1099–1119.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. Schmahmann JD, Sherman JC . The cerebellar cognitive affective syndrome. Brain 1998; 121: 561–579.

    PubMed  Article  Google Scholar 

  31. 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.

    CAS  Article  PubMed  Google Scholar 

  32. Brambilla P, Harenski K, Nicoletti M, Mallinger AG, Frank E, Kupfer DJ et al. MRI study of posterior fossa structures and brain ventricles in bipolar patients. J Psychiatr Res 2001; 35: 313–322.

    CAS  PubMed  Article  Google Scholar 

  33. Strakowski SM, Wilson DR, Tohen M, Woods BT, Douglass AW, Stoll AL . Structural brain abnormalities in first-episode mania. Biol Psychiatry 1993; 33: 602–609.

    CAS  PubMed  Article  Google Scholar 

  34. Altshuler LL, Curran JG, Hauser P, Mintz J, Denicoff K, Post R . T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis. Am J Psychiatry 1995; 152: 1139–1144.

    CAS  PubMed  Article  Google Scholar 

  35. Adler CM, Holland SK, Schmithorst V, Wilke M, Weiss K, Pan H et al Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study. Bipolar Disord 2004; 6: 197–203.

    PubMed  Article  Google Scholar 

  36. Tsai G, Coyle JT . N-acetylaspartate in neuropsychiatric disorders. Prog Neurobiol 1995; 46: 531–540.

    CAS  PubMed  Article  Google Scholar 

  37. Kato T, Inubushi T, Kato N . Magnetic resonance spectroscopy in affective disorders. J Neuropsychiatry Clin Neurosci 1998; 10: 133–147.

    CAS  PubMed  Article  Google Scholar 

  38. Moore C, Breeze JL, Gruber S, Babb S, Frederick B, Villafuerte R et al. Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulated cortex. Bipolar Disord 2000; 2: 207–216.

    CAS  Article  PubMed  Google Scholar 

  39. Castillo M, Kwock L, Courvoisie H, Hooper S, Proton MR . Spectroscopy in children with bipolar affective disorder: preliminary observations. Am J Neuroradiol 2000; 21: 832–838.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Cecil K, DelBello MP, Morey R, Strakowski SM . Frontal lobe differences in bipolar disorder as determined by proton MR spectroscopy. Bipolar Disord 2002; 4: 357–365.

    CAS  Article  PubMed  Google Scholar 

  41. Cecil KM, DelBello MP, Sellers MC, Strakowski SM, Proton MR . Spectroscopy of the frontal lobe and cerebellar vermis in children with a mood disorder and a familial risk for bipolar disorders. J Child Adol Psychopharm 2003; 13: 545–555.

    Article  Google Scholar 

  42. Chang K, Adleman N, Dienes K, Barnea-Goraly N, Reiss A, Ketter T . Decreased N-Acetylaspartate in children with familial bipolar disorder. Biol Psychiatry 2003; 53: 1059–1065.

    CAS  Article  PubMed  Google Scholar 

  43. Davanzo P, Thomas M, Yue K, Oshiro T, Belin T, Strober M et al. Decreased anterior cingulated myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder. Neuropsychopharmacology 2001; 24: 359–369.

    CAS  Article  PubMed  Google Scholar 

  44. Davanzo P, Yue K, Thomas M, Belin T, Mintz J, Venkatraman T et al. Proton magnetic resonance spectroscopy of bipolar disorder vs intermittent explosive disorder in children and adolescents. Am J Psychiatry 2003; 160: 144–152.

    Article  Google Scholar 

  45. Winsberg M, Sachs N, Tate D, Adalsteinsson E, Spielman D, Ketter T . Decreased dorsolateral prefrontal n-acetyl-aspartate in bipolar disorder. Biol Psychiatry 2000; 47: 475–481.

    CAS  PubMed  Article  Google Scholar 

  46. Dager SR, Friedman SD, Parow A, Demopulos C, Stoll AL, Lyoo IK, Dunner DL, Renshaw PF . Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry 2004; 61: 450–458.

    CAS  Article  PubMed  Google Scholar 

  47. Bertolino A, Frye M, Callicott J, Mattay V, Rakow R, Shelton-Repella J et al. Neuronal pathology in the hippocampal area of patients with bipolar disorder. Biol Psychiatry 2003; 53: 906–913.

    PubMed  Article  Google Scholar 

  48. Deicken R, Pegues M, Anzalone S, Feiwell R, Soher B . Lower concentration of hippocampal N-Acetylaspartate in familial bipolar I disorder. Am J Psychiatry 2003; 160: 873–882.

    PubMed  Article  Google Scholar 

  49. Ohara K, Isoda H, Suzuki Y, Takehara Y, Ochiai M, Takeda H et al. Proton magnetic resonance spectroscopy of the lenticular nuclei in bipolar I affective disorder. Psychiatry Res 1998; 84: 55–60.

    CAS  PubMed  Article  Google Scholar 

  50. Deicken R, Eliaz Y, Feiwell R, Schuff N . Increased thalmamic N-acetylaspartate in male patients with familial bipolar disorder. Psychiatry Res 2001; 106: 35–45.

    CAS  PubMed  Article  Google Scholar 

  51. Yildiz A, Sachs G, Dorer D, Renshaw P . 31P Nuclear magnetic resonance spectroscopy findings in bipolar illness: meta-analysis. Psychiatry Res 2001; 106: 181–191.

    CAS  PubMed  Article  Google Scholar 

  52. Moore G, Bebchuk J, Parrish J, Faulk M, Arfken C, Strahl-Bevacqua J et al. Temporal dissociation between lithium-induced changes in frontal lobe myo-inositol and clinical response in manic depressive illness. Am J Psychiatry 1999; 156: 1902–1908.

    CAS  PubMed  Google Scholar 

  53. Moore G, Bebchuk J, Hasanat K, Chen G, Seraji-Bozorgzad N, Wild I et al. Lithium increases N-acetyl-asparatate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects? Biol Psychiatry 2000; 48: 1–8.

    CAS  PubMed  Article  Google Scholar 

  54. Silverstone P, Wu R, O’Donnell T, Ulrich M, Asghar S, Hanstock C . Chronic treatment with lithium, but not sodium valproate, increases cortical acetyl-aspartate concentrations in euthymic bipolar patients. Int Clin Psychopharmacol 2003; 18: 73–79.

    Article  PubMed  Google Scholar 

  55. Silverstone P, Wu R, O’Donnell T, Ulrich M, Asghar S, Hanstock C . Chronic treatment with both lithium and sodium valproate may normalize phosphoinositol cycle activity in bipolar patients. Hum Psychopharmacol 2002; 17: 321–327.

    CAS  PubMed  Article  Google Scholar 

  56. Lyoo I, Demopulos C, Hirashima F, Ahn K, Renshaw P . Oral choline decreases brain purine levels in lithium-treated subjects with rapid in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy. Bipolar Disord 2003; 5: 300–306.

    CAS  Article  PubMed  Google Scholar 

  57. Soares J, Boada F, Spencer S, Mallinger A, Dippold C, Wells K et al. Brain lithium concentrations in bipolar disorder patients: preliminary (7)Li magnetic resonance studies at 3T. Biol Psychiatry 2001; 49: 437–443.

    CAS  PubMed  Article  Google Scholar 

  58. Charles HC, Lazeyras F, Krishnan RR, Boyko OB, Payne M, Moore D . Brain choline in depression: In vivo detection of potential pharmacodynamic effects of antidepressant therapy using hydrogen localized spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18: 1121–1127.

    CAS  Article  PubMed  Google Scholar 

  59. Hamakawa H, Kato T, Murashita J, Kato N . Quantitative proton magnetic spectroscopy of the basal ganglia in patients with affective disorders. Eur Arch Psychiatry Clin Neurosci 1998; 248: 53–58.

    CAS  PubMed  Article  Google Scholar 

  60. Renshaw PF, Lafer B, Babb S, Fava M, Stoll A, Christensen JD et al. Basal ganglia choline levels in depression and response to fluoxetine treatment: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry 1997; 41: 837–843.

    CAS  Article  PubMed  Google Scholar 

  61. Miller BL, Chang L, Booth R, Ernst T, Cornford M, Nikas D et al. In vivo H-1 MRS choline correlation with in vitro chemistry histology. Life Sci 1996; 58: 1929–1935.

    CAS  Article  PubMed  Google Scholar 

  62. Domino EF . Proton MRS of choline in brain and red blood cells: effects of lithium therapy. In: Nasrallah HA, Pettegrew JW (eds). NMR Spectorscopy in Psychiatric Brain Disorders. American Psychiatric Press Inc.: Washington DC, 1995 pp 199–212.

    Google Scholar 

  63. Hallcher LM, Sherman WR . The effect of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J Bio Chem 1980; 255: 10896–10901.

    CAS  Google Scholar 

  64. Blumberg HP, Stern E, Martinez D, Ricketts S, de Asis J, White T et al. Increased anterior cingulate and caudate activity in bipolar mania. Biol Psychiatry 2000; 48: 1045–1052.

    CAS  Article  PubMed  Google Scholar 

  65. Blumberg HP, Stern E, Ricketts S, Martinez D, de Asis J, White T et al. Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. Am J Psychiatry 1999; 156: 1986–1988.

    CAS  PubMed  Google Scholar 

  66. Rubinsztein JS, Fletcher PC, Rogers RD, Ho LW, Aigbirhio FI, Paykel ES et al. Decision-making in mania: a PET study. Brain 2001; 124: 2550–2563.

    CAS  PubMed  Article  Google Scholar 

  67. Curtis VA, Dixon TA, Morris RG, Bullmore ET, Brammer MJ, Williams SC et al. Differential frontal activation in schizophrenia and bipolar illness during verbal fluency. J Affect Disord 2001; 66: 111–121.

    CAS  PubMed  Article  Google Scholar 

  68. Yurgelun-Todd D, Gruber SA, Kanayama G, Killgore WD, Baird AA, Young AD . FMRI during affect discrimination in bipolar disorder. Bipolar Disord 2000; 2: 237–248.

    CAS  PubMed  Article  Google Scholar 

  69. Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC 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.

    PubMed  Article  Google Scholar 

  70. Strakowski SM, Adler CM, Holland SK, Mills NP, DelBello MP . A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology 2004 (in press).

  71. Baxter LR, Phelps ME, Mazziotta JC, Schwartz JM, Gerner RH, Selin CE et al. Cerebral metabolic rates for glucose in mood disorders: studies with positron emission tomography and fluorodeoxyglucose F 18. Arch Gen Psychiatry 1985; 42: 441–447.

    PubMed  Article  Google Scholar 

  72. O’Connell RA, Van Heertum RL, Luck D, Yudd AP, Cueva JE, Billick SB et al. Single photon emission computed tomography of the brain in acute mania and schizophrenia. J Neuroimaging 1995; 5: 101–104.

    PubMed  Article  Google Scholar 

  73. Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski P, Lacadie C et al. Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. Am J Psychiatry 2003; 160: 1345–1347.

    PubMed  Article  Google Scholar 

  74. Ketter TA, Kimbrell TA, George MS, Dunn RT, Speer AM, Benson BE et al. Effects of mood and subtype on cerebral glucose metabolism in treatment-resistant bipolar disorder. Biol Psychiatry 2001; 49: 97–109.

    CAS  Article  PubMed  Google Scholar 

  75. Caliguri MP, Brown GG, Meloy MJ, Eberson SC, Kindermann SS, Frank LR et 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.

    Article  Google Scholar 

  76. Ichimiya T, Suhara T, Sudo Y, Okubo Y, Nakayama K, Nankai M et al. Serotonin transporter binding in patients with mood disorders: a PET study with [111C] (+)McN5652. Biol Psychiatry 2002; 51: 715–722.

    CAS  PubMed  Article  Google Scholar 

  77. Suhara T, Nakayama K, Inoue O, Fukuda H, Shimizu M, Mori A et al. D1 dopamine receptor binding in mood disorders measured by positron emission tomography. Psychopharmacology (Berlin) 1992; 106: 14–18.

    CAS  Article  Google Scholar 

  78. Wong DF, Wagner Jr HN, Pearlson G, Dannals RF, Links JM, Ravert HT et al. Dopamine receptor binding of C-11-3-N-methylspiperone in the caudate in schizophrenia and bipolar disorder: a preliminary report. Psychopharmacol Bull 1985; 21: 595–598.

    CAS  PubMed  Google Scholar 

  79. Anand A, Verhoeff P, Seneca N, Zoghbi SS, Seibyl JP, Charney DS et al. Brain SPECT imaging of amphetamine-induced dopamine release in euthymic bipolar disorder patients. Am J Psychiatry 2000; 157: 1108–1114.

    CAS  Article  PubMed  Google Scholar 

  80. Yatham LN, Liddle PF, Lam RW, Shiah IS, Lane C, Stoessl AJ et al. PET study of the effects of valproate on dopamine D(2) receptors in neuroleptic- and mood-stabilizer-naive patients with nonpsychotic mania. Am J Psychiatry 2002; 159: 1718–1723.

    PubMed  Article  Google Scholar 

  81. Yatham LN, Liddle PF, Shiah IS, Lam RW, Ngan E, Scarrow G et al. PET study of [(18)F]6-fluoro-L-dopa uptake in neuroleptic- and mood-stabilizer-naïve first-episode nonpsychotic mania: effects of treatment with divalproex sodium. Am J Psychiatry 2002; 159: 768–774.

    PubMed  Article  Google Scholar 

  82. Pearlson GD, Wong DF, Tune LE, Ross CA, Chase GA, Links JM et al. In vivo D2 dopamine receptor density in psychotic and nonpsychotic patients with bipolar disorder. Arch Gen Psychiatry 1995; 52: 471–477.

    CAS  Article  PubMed  Google Scholar 

  83. Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA et al. Reciprocal limbic–cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 1999; 156: 675–682.

    CAS  PubMed  Google Scholar 

  84. Strakowski SM, Adler CM, Holland SK, DelBello MP, Schmithorst V . Neural activation during facial affect recognition in euthymic bipolar disorder. Biol Psychiatry 2001; 49: 81S.

    Article  Google Scholar 

  85. DelBello MP, Adler CM, Mills NP, Strakowski SM . Functional magnetic resonance imaging (fMRI) study of the continuous performance test in unmedicated manic bipolar adolescents. 41st annual meeting of ACNP, San Juan, PR, December 2002.

  86. Strakowski SM, Sax KW . Secondary mania: a model of the pathophysiology of bipolar disorder?. In: Soares JC, Gershon S (eds) Basic Mechanisms and Therapeutic Implications of Bipolar Disorder. Marcel Dekker, Inc.: New York, 2000 pp 13–30.

    Google Scholar 

  87. Cummings JL . Frontal–subcortical circuits and human behavior. Arch Neurol 1993; 50: 873–880.

    CAS  Article  PubMed  Google Scholar 

  88. Soares JC, Mann JJ . The anatomy of mood disorders—review of structural neuroimaging studies. Biol Psychiatry 1997; 41: 86–106.

    CAS  PubMed  Article  Google Scholar 

  89. Starkstein SE, Federoff P, Berthier ML, Robinson RG . Manic-depressive and pure manic states after brain lesions. Biol Psychiatry 1991; 29: 149–158.

    CAS  PubMed  Article  Google Scholar 

  90. Ketter TA, Wang PW, Dieckmann NF, Lembke A, Becker OV, Camilleri C . Brain anatomic circuits and the pathophysiology of affective disorders. In: Soares JC (ed). Brain Imaging in Affective Disorders. Marcel Dekker: New York, 2002 pp 79–118.

    Google Scholar 

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Strakowski, S., DelBello, M. & Adler, C. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry 10, 105–116 (2005). https://doi.org/10.1038/sj.mp.4001585

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Keywords

  • MRI
  • MRS
  • fMRI
  • neuroimaging
  • neurophysiology

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