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Neurobiological trait abnormalities in bipolar disorder

Molecular Psychiatry volume 14, pages 833–846 (2009)Cite this article

Abstract

Dissecting trait neurobiological abnormalities in bipolar disorder (BD) from those characterizing episodes of mood disturbance will help elucidate the aetiopathogenesis of the illness. This selective review highlights the immunological, neuroendocrinological, molecular biological and neuroimaging abnormalities characteristic of BD, with a focus on those likely to reflect trait abnormalities by virtue of their presence in euthymic patients or in unaffected relatives of patients at high genetic liability for illness. Trait neurobiological abnormalities of BD include heightened pro-inflammatory function and hypothalamic–pituitary–adrenal axis dysfunction. Dysfunction in the intracellular signal transduction pathway is indicated by elevated protein kinase A activity and altered intracellular calcium signalling. Consistent neuroimaging abnormalities include the presence of ventricular enlargement and white matter abnormalities in patients with BD, which may represent intermediate phenotypes of illness. In addition, spectroscopy studies indicate reduced prefrontal cerebral N-acetylaspartate and phosphomonoester concentrations. Functional neuroimaging studies of euthymic patients implicate inherently impaired neural networks subserving emotional regulation, including anterior limbic, ventral and dorsal prefrontal regions. Despite heterogeneous samples and conflicting findings pervading the literature, there is accumulating evidence for the existence of neurobiological trait abnormalities in BD at various scales of investigation. The aetiopathogenesis of BD will be better elucidated by future clinical research studies, which investigate larger and more homogenous samples and employ a longitudinal design to dissect neurobiological abnormalities that are underlying traits of the illness from those related to episodes of mood exacerbation or pharmacological treatment.

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References

  1. Hasler G, Drevets WC, Gould TD, Gottesman II, Manji HK . Toward constructing an endophenotype strategy for bipolar disorders. Biol Psychiatry 2006; 60: 93–105.

    Article  PubMed  Google Scholar 

  2. Glahn DC, Bearden CE, Niendam TA, Escamilla MA . The feasibility of neuropsychological endophenotypes in the search for genes associated with bipolar affective disorder. Bipolar Disord 2004; 6: 171–182.

    Article  PubMed  Google Scholar 

  3. Ferrier IN, Stanton BR, Kelly TP, Scott J . Neuropsychological function in euthymic patients with bipolar disorder. Br J Psychiatry 1999; 175: 246–251.

    Article  CAS  PubMed  Google Scholar 

  4. Quraishi S, Frangou S . Neuropsychology of bipolar disorder: a review. J Affect Disord 2002; 72: 209–226.

    Article  PubMed  Google Scholar 

  5. Robinson LJ, Ferrier IN . Evolution of cognitive impairment in bipolar disorder: a systematic review of cross-sectional evidence. Bipolar Disord 2006; 8: 103–116.

    Article  PubMed  Google Scholar 

  6. Turnbull AV, Rivier C . Regulation of the HPA Axis by cytokines. Brain Behav Immun 1995; 9: 253–275.

    Article  CAS  PubMed  Google Scholar 

  7. Besedovsky HO, Del Rey A . Immune–neuroendocrine interactions: facts and hypotheses. Endocr Rev 1996; 17: 64–102.

    Article  CAS  PubMed  Google Scholar 

  8. Turnbull AV, Rivier CL . Regulation of the hypothalamic–pituitary–adrenal axis by cytokines: actions and mechanisms of action. Physiol Rev 1999; 79: 1–71.

    Article  CAS  PubMed  Google Scholar 

  9. Kiecolt-Glaser JK, Glaser R . Depression and immune function: central pathways to morbidity and mortality. J Psychosom Res 2002; 53: 873–876.

    Article  PubMed  Google Scholar 

  10. Papanicolaou DA, Yanovski JA, Cutler GBJ, Chrousos GP, Nieman LK . The pathophysiology roles of interleukin 6 in human disease. Ann Int Med 1998; 128: 127–134.

    Article  CAS  PubMed  Google Scholar 

  11. Maes M . Major depression and activation of the inflammatory response system. Adv Exp Med Biol 1999; 461: 25–46.

    Article  CAS  PubMed  Google Scholar 

  12. Song C, Dinan TG, Leonard BE . Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord 1994; 30: 283–288.

    Article  CAS  PubMed  Google Scholar 

  13. Yirmiya R, Pollak Y, Morag M, Reichenberg A, Barak O, Avitsur R et al. Illness, cytokines and depression. Ann N Y Acad Sci 2000; 917: 478–487.

    Article  CAS  PubMed  Google Scholar 

  14. Fitzgerald P, O’Brien SM, Scully P, Rijkers K, Scott LV, Dinan TG . Cutaneous glucocorticoid receptor sensitivity and pro-inflammatory cytokine levels in antidepressant-resistant depression. Psychol Med 2006; 36: 37–43.

    Article  PubMed  Google Scholar 

  15. Breunis MN, Kupka RW, Nolen WA, Suppes T, Denicoff KD, Leverich GS et al. High numbers of circulating activated T cells and raised levels of serum IL-2 receptor in bipolar disorder. Biol Psychiatry 2003; 53: 157–165.

    Article  CAS  PubMed  Google Scholar 

  16. Liu H-C, Yang Y-Y, Chou Y-M, Chen K-P, Shen WW, Leu S-J . Immunologic variables in acute mania of bipolar disorder. J Neuroimmunol 2004; 150: 116–122.

    Article  CAS  PubMed  Google Scholar 

  17. O’Brien SM, Scully P, Scott LV, Dinan TG . Cytokine profiles in bipolar affective disorder: focus on acutely ill patients. J Affect Disord 2006; 90: 263–267.

    Article  PubMed  CAS  Google Scholar 

  18. Kim Y-K, Jung H-G, Myint A-M, Kim H, Park S-H . Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder. J Affect Disord 2007; 104: 91–95.

    Article  CAS  PubMed  Google Scholar 

  19. Boufidou F, Nikolaou C, Alevizos B, Liappas IA, Christodoulou GN . Cytokine production in bipolar affective disorder patients under lithium treatment. J Affect Disord 2004; 82: 309–313.

    Article  CAS  PubMed  Google Scholar 

  20. Maes M, Delange J, Ranjan R, Meltzer HY, Desnyder R, Cooremans W et al. Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatry Res 1997; 66: 1–11.

    Article  CAS  PubMed  Google Scholar 

  21. Maes M, Bosmans E, Calabrese J, Smith R, Meltzer HY . Interleukin-2 and interleukin-6 in schizophrenia and mania: effects of neuroleptics and mood stabilizers. J Psychiatr Res 1995; 29: 141–152.

    Article  CAS  PubMed  Google Scholar 

  22. Gibbons JL, McHugh PR . Plasma cortisol in depressive illness. J Psychiatr Res 1962; 1: 162–171.

    Article  CAS  PubMed  Google Scholar 

  23. Carroll BJ . Use of the dexamethasone test in depression. J Clin Psychiatry 1982; 43: 44–50.

    CAS  PubMed  Google Scholar 

  24. Holsboer F, von Bardeleben U, Wiedemann K, Muller OA, Stalla GK . Serial assessment of corticotropin-releasing hormone response after dexamethasone in depression. Implications for pathophysiology of DST non-suppression. Biol Psychiatry 1987; 22: 228–234.

    Article  CAS  PubMed  Google Scholar 

  25. Heuser I, Yassouridis A, Holsboer F . The combined dexamethasone/CRH test: a refined laboratory test for psychiatric disorders. J Psychiatr Res 1994; 28: 341–356.

    Article  CAS  PubMed  Google Scholar 

  26. Pariante CM . The glucocorticoid receptor: part of the solution or part of the problem? J Psychopharmacol 2006; 20 (Suppl): 79–84.

    Article  PubMed  Google Scholar 

  27. Holsboer F, Lauer CJ, Schreiber W, Krieg JC . Altered hypothalamic–pituitary–adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology 1995; 62: 340–347.

    Article  CAS  PubMed  Google Scholar 

  28. Schmider J, Lammers C-H, Gotthardt U, Dettling M, Holsboer F, Heuser I . Combined Dexamethasone/Corticotropin-Releasing Hormone Test in acute and remitted manic patients, in acute depression and in normal controls:I. Biol Psychiatry 1995; 38: 797–802.

    Article  CAS  PubMed  Google Scholar 

  29. Rybakowski JK, Twardowska K . The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness. J Psychiatr Res 1999; 33: 363–370.

    Article  CAS  PubMed  Google Scholar 

  30. Watson S, Gallagher P, Ritchie JC, Ferrier N, Young AH . Hypothalamic–pituitary–adrenal axis function in patients with bipolar disorder. Br J Psychiatry 2004; 184: 496–502.

    Article  PubMed  Google Scholar 

  31. Watson S, Thompson JM, Ritchie JC, Ferrier IN, Young AH . Neuropsychological impairment in bipolar disorder: the relationship with glucocorticoid receptor function. Bipolar Disord 2006; 8: 85–90.

    Article  CAS  PubMed  Google Scholar 

  32. Knijff EM, Breunis MN, van Geest MC, Kupka RW, Ruwhof C, de Wit HJ et al. A relative resistance of T cells to dexamethasone in bipolar disorder. Bipolar Disord 2006; 8: 740–750.

    Article  CAS  PubMed  Google Scholar 

  33. Bauer ME, Papadopoulos A, Poon L, Perks P, Lightman SL, Vheckley S et al. Altered glucocorticoid immunoregulation in treatment resistant depression. Psychoneuroendocrinology 2003; 28: 49–65.

    Article  CAS  PubMed  Google Scholar 

  34. Ryan MCM, Sharifi N, Condren R, Thakore JH . Evidence of basal pituitary–adrenal overactivity in first-episode, drug naive patients with schizophrenia. Psychoneuroendocrinology 2004; 29: 1065–1070.

    Article  CAS  PubMed  Google Scholar 

  35. Gallagher P, Watson S, Smith MS, Young AH, Ferrier IN . Plasma cortisol–dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder. Schizophr Res 2007; 90: 258–265.

    Article  PubMed  Google Scholar 

  36. Young LT, Bakish D, Beaulieu S . The neurobiology of treatment response to antidepressants and mood stabilising medications. J Psychiatry Neurosci 2002; 27: 260–265.

    PubMed  PubMed Central  Google Scholar 

  37. Aydemir C, Yalcin ES, Aksaray S, Kisa C, Yildirim SG, Uzbay T et al. Brain derived neurotrophic factor changes in serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 1256–1260.

    Article  CAS  PubMed  Google Scholar 

  38. Gonul AS, Akdeniz F, Taneli F, Donat O, Eker C, Vahip S . Effect of treatment on serum brain derived neurotrophic factor levels in depressed patients. Eur Arch Clin Neurosci 2005; 255: 381–386.

    Google Scholar 

  39. Quiroz JA, Singh J, Gould TD, Denicoff KD, Zarate Jr CA, Manji HK . Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology. Mol Psychiatry 2004; 9: 756–776.

    Article  CAS  PubMed  Google Scholar 

  40. Tardito D, Mori S, Racagni G, Smeraldi E, Zanardi R, Perez J . Protein kinase activity in platelets from patients with bipolar disorder. J Affect Disord 2003; 76: 249–253.

    Article  CAS  PubMed  Google Scholar 

  41. Perez J, Tardito D, Mori S, Racagni G, Smeraldi E, Zanardi R . Abnormalities of cyclic adenosine monophosphate signalling in platelets from untreated patients with bipolar disorder. Arch Gen Psychiatry 1999; 56: 248–253.

    Article  CAS  PubMed  Google Scholar 

  42. Karege F, Schwald M, Papadimitriou P, Lachausse C, Cisse M . The cAMP-dependent protein kinase A and brain-derived neurotrophic factor expression in lymphoblast cells of bipolar affective disorder. J Affect Disord 2004a; 79: 187–192.

    Article  CAS  PubMed  Google Scholar 

  43. Karege F, Schwald M, Kouaissi RE . Drug-induced decrease of protein kinase A activity reveals alteration in BDNF expression of bipolar affective disorder. Neuropsychopharmacology 2004b; 29: 805–812.

    Article  CAS  PubMed  Google Scholar 

  44. Monteleone P, Serritella C, Martiadis V, Maj M . Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic patients with bipolar I and II disorders. Bipolar Disord 2008; 10: 95–100.

    Article  CAS  PubMed  Google Scholar 

  45. Cunha ABM, Frey BN, Andreazza AC, Goi JD, Rosa AR, Goncalves CA et al. Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett 2006; 398: 215–219.

    Article  CAS  PubMed  Google Scholar 

  46. Machado-Viera R, Dietrich MO, Leke R, Cereser VH, Zanatto V, Kapczinski F et al. Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar patients during manic episode. Biol Psychiatry 2007; 61: 142–144.

    Article  CAS  Google Scholar 

  47. Gama CS, Andreazza AC, Kunz M, Berk M, Belmonte-de-Abreu PS, Kapczinski F . Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder. Neurosci Lett 2007; 420: 45–48.

    Article  CAS  PubMed  Google Scholar 

  48. Palomino A, Vallejo-Illarramendi A . Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients. Schizophr Res 2006; 86: 321–322.

    Article  PubMed  Google Scholar 

  49. Young LT, Li PP, Kamble A, Siu KP, Warsh JJ . Mononuclear leukocyte levels of G proteins in depressed patients with bipolar disorder or major depressive disorder. Am J Psychiatry 1994; 151: 594–596.

    Article  CAS  PubMed  Google Scholar 

  50. Manji HK, Chen G, Shimon H, Hsiao JK, Potter WZ, Belmaker RH . Guanine nucleotide-binding proteins in bipolar affective disorder. Effects of long-term lithium treatment. Arch Gen Psychiatry 1995; 52: 135–144.

    Article  CAS  PubMed  Google Scholar 

  51. Mitchell PB, Manji HK, Chen G, Jolkovsky L, Smith-Jackson E, Denicott K et al. High levels of Gsα in platelets of euthymic patients with bipolar affective disorder. Am J Psychiatry 1997; 154: 218–223.

    Article  CAS  PubMed  Google Scholar 

  52. Avissar S, Nechamkin Y, Barki-Harrington L, Roitman G, Schreiber G . Differential G protein measures in mononuclear leukocytes of patients with bipolar mood disorder are state dependent. J Affect Disord 1997; 43: 85–93.

    Article  CAS  PubMed  Google Scholar 

  53. Schreiber G, Avissar S, Danon A, Belmaker RH . Hyperfunctional G proteins in mononuclear leukocytes of patients with mania. Biol Psychiatry 1991; 29: 273–280.

    Article  CAS  PubMed  Google Scholar 

  54. Alda M, Keller D, Grof E, Turecki G, Cavazzoni P, Duffy A et al. Is lithium response related to Gsα levels in transformed lymphoblasts from subjects with bipolar disorder? J Affect Disord 2001; 65: 117–122.

    Article  CAS  PubMed  Google Scholar 

  55. Hahn CG, Umapathy C, Wang HY, Koneru R, Levinson DF, Friedman E . Lithium and valproic acid treatments reduce PKC activation and receptor–G protein coupling in platelets of bipolar manic patients. J Psychiatr Res 2005; 39: 355–363.

    Article  PubMed  Google Scholar 

  56. Bezchlibnyk Y, Young LT . The neurobiology of bipolar disorder: focus on signal transduction pathways and the regulation of gene expression. Can J Psychiatry 2002; 47: 135–148.

    Article  PubMed  Google Scholar 

  57. Brown AS, Mallinger AG, Renbaum LC . Elevated platelet membrane phosphatidylinositol-4,5-bisphosphate in bipolar mania. Am J Psychiatry 1993; 150: 1252–1254.

    Article  CAS  PubMed  Google Scholar 

  58. Soares JC, Dippold CS, Wells KF, Frank E, Kupfer DJ, Mallinger AG . Increased platelet membrane phosphatidylinositol-4,5-bisphosphate in drug-free depressed bipolar patients. Neurosci Lett 2001; 299: 150–152.

    Article  CAS  PubMed  Google Scholar 

  59. Wang H-Y, Markowitz P, Levinson D, Undie AS, Friedman E . Increased membrane-associated protein kinase C activity and translocation in blood platelets from bipolar affective disorder patients. J Psychiatr Res 1999; 33: 171–179.

    Article  CAS  PubMed  Google Scholar 

  60. Soares JC, Mallinger AG, Dippold CS, Frank E, Kupfer DJ . Platelet membrane phospholipids in euthymic bipolar disorder patients: are they affected by lithium treatment? Biol Psychiatry 1999; 45: 453–457.

    Article  CAS  PubMed  Google Scholar 

  61. Soares JC, Mallinger AG, Dippold CS, Forster Wells K, Frank E, Kupfer DJ . Effects of lithium on platelet membrane phosphoinositides in bipolar disorder patients: a pilot study. Psychopharmacology 2000; 149: 12–16.

    Article  CAS  PubMed  Google Scholar 

  62. Berridge MJ, Downes CP, Hanley MR . Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands. Biochem J 1982; 206: 587–595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Manji HK, Potter WZ, Lenox RH . Signal transduction pathways: molecular targets for lithium's actions. Arch Gen Psychiatry 1995; 52: 531–543.

    Article  CAS  PubMed  Google Scholar 

  64. Manji HK, Lenox RH . Signaling: cellular insights into the pathophysiology of bipolar disorder. Biol Psychiatry 2000; 48: 518–530.

    Article  CAS  PubMed  Google Scholar 

  65. Emamghoreishi M, Schlichter L, Li PP, Parikh S, Sen J, Kamble A et al. High intracellular calcium concentrations in transformed lymphoblasts from subjects with bipolar I disorder. Am J Psychiatry 1997; 154: 976–982.

    Article  CAS  PubMed  Google Scholar 

  66. Emamghoreishi M, Li PP, Schlichter L, Parikh S, Cooke R, Warsh JJ . Associated disturbances in calcium homeostasis and G protein-mediated cAMP signalling in bipolar I disorder. Biol Psychiatry 2000; 48: 665–673.

    Article  CAS  PubMed  Google Scholar 

  67. Perova T, Wasserman MJ, Li PP, Warsh JJ . Hyperactive intracellular calcium dynamics in B lymphoblasts from patients with bipolar I disorder. Int J Neuropsychopharmacol 2008; 11: 185–196.

    Article  CAS  PubMed  Google Scholar 

  68. El Khoury A, Petterson U, Kallner G, Aberg-Wistedt A, Stain-Malmgren R . Calcium homeostasis in long-term lithium-treated women with bipolar affective disorder. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 1063–1069.

    Article  CAS  PubMed  Google Scholar 

  69. Dubovsky SL, Thomas M, Hijazi A, Murphy J . Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci 1994; 243: 229–234.

    Article  CAS  PubMed  Google Scholar 

  70. Hahn C-G, Gomez G, Restrepo D, Friedman E, Josiassen R, Pribitkin EA et al. Aberrant intracellular calcium signalling in olfactory neurons from patients with bipolar disorder. Am J Psychiatry 2005; 162: 616–618.

    Article  PubMed  Google Scholar 

  71. Kato T, Ishiwata M, Mori K, Washizuka S, Tajima O, Akiyama T et al. Mechanisms of altered Ca2+ signalling in transformed lymphoblastoid cells from patients with bipolar disorder. Int J Neuropsychopharmacol 2003; 6: 379–389.

    Article  CAS  PubMed  Google Scholar 

  72. Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, Heckers S . Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychiatry 2004; 61: 300–308.

    Article  CAS  PubMed  Google Scholar 

  73. Elkis H, Friedman L, Wise A, Meltzer HY . Meta-analysis of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Arch Gen Psychiatry 1995; 52: 735–746.

    Article  CAS  PubMed  Google Scholar 

  74. Pearlson GD, Veroff AE . Computerised tomographic scan changes in manic-depressive illness. Lancet 1981; 2: 470.

    Article  CAS  PubMed  Google Scholar 

  75. McDonald C, Zanelli J, Rabe-Hesketh S, Ellison-Wright I, Sham PC, Kalidindi S et al. Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder. Biol Psychiatry 2004; 56: 411–417.

    Article  PubMed  Google Scholar 

  76. Kempton MJ, Geddes JR, Ettinger U, Williams SCR, Grasby PM . Meta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry 2008; 65: 1017–1032.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  78. McDonald C, Marshall N, Sham PC, Bullmore ET, Schulze K, Chapple B et al. Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. Am J Psychiatry 2006; 163: 478–487.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  80. Strasser HC, Lilyestrom J, Ashby ER, Honeycutt NA, Schretlen DJ, Pulver AE et al. Hippocampal and ventricular volumes in psychotic and non-psychotic bipolar patients compared with schizophrenia patients and community control subjects: a pilot study. Biol Psychiatry 2005; 57: 633–639.

    Article  PubMed  Google Scholar 

  81. Hauser P, Matochik J, Altshuler LL, Denicoff KD, Conrad A, Li X et al. 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.

    Article  CAS  PubMed  Google Scholar 

  82. 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 or schizophrenia. Biol Psychiatry 2000; 48: 147–162.

    Article  CAS  PubMed  Google Scholar 

  83. 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.

    CAS  PubMed  Google Scholar 

  84. 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.

    Article  PubMed  Google Scholar 

  85. Strakowski SM, Del Bello 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.

    Article  CAS  PubMed  Google Scholar 

  86. Pearlson GD, Barta PE, Powers RE, Menon RR, Richards SS, Aylward EH et al. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry 1997; 41: 1–4.

    Article  CAS  PubMed  Google Scholar 

  87. Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC et al. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry 2003; 60: 1201–1208.

    Article  PubMed  Google Scholar 

  88. Rosso IM, Killgore WD, Cintron CM, Gruber SA, Tohen M, Yurgelun-Todd DA . Reduced amygdala volumes in first episode bipolar disorder and correlation with cerebral white matter. Biol Psychiatry 2007; 61: 743–749.

    Article  PubMed  Google Scholar 

  89. Lopez-Larson MP, Del Bello MP, Zimmerman ME, Schwiers ML, Strakowski SM . Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry 2002; 52: 93–100.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  91. Sharma V, Menon RR, Carr TJ, Densmore M, Mazmanian D, Williamson PC . An MRI study of subgenual prefrontal cortex in patients with familial and non-familial bipolar I disorder. J Affect Disord 2003; 77: 167–171.

    Article  PubMed  Google Scholar 

  92. Zimmerman ME, Del Bello MP, Getz GE, Shear PK, Strakowski SM . Anterior cingulate subregion volumes and executive function in bipolar disorder. Bipolar Disord 2006; 8: 281–288.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  94. McIntosh AM, Job DE, Moorhead TW, Harrison LK, Forrester K, Lawrie SM et al. Voxel-based morphometry of patients with schizophrenia or bipolar disorder and their unaffected relatives. Biol Psychiatry 2004; 56: 544–552.

    Article  PubMed  Google Scholar 

  95. Nugent AC, Milham MP, Bain EE, Mah L, Cannon DM, Marrett S et al. Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry. Neuroimage 2006; 30: 485–497.

    Article  PubMed  Google Scholar 

  96. Lyoo IK, Sung YH, Dager SR, Friedman SD, Lee J-Y, Kim SJ et al. Regional cerebral cortical thinning in bipolar disorder. Bipolar disord 2006; 8: 65–74.

    Article  PubMed  Google Scholar 

  97. Chen X, Wen W, Malhi GS, Ivanovski B, Sachdev PS . Regional gray matter changes in bipolar disorder: a voxel-based morphometric study. Aust N Z J Psychiatry 2007; 41: 327–336.

    Article  PubMed  Google Scholar 

  98. Adler CM, Levine AD, Del Bello MP, Strakowski SM . Changes in gray matter volume in patients with bipolar disorder. Biol Psychiatry 2005; 58: 151–157.

    Article  PubMed  Google Scholar 

  99. Lochhead RA, Parsey RV, Oquendo MA, Mann JJ . Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimised voxel-based morphometry. Biol Psychiatry 2004; 55: 1154–1162.

    Article  PubMed  Google Scholar 

  100. 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.

    Article  PubMed  Google Scholar 

  101. Bearden CE, Thompson PM, Dalwani M, Hayashi KM, Lee AD, Nicoletti M et al. Greater cortical gray matter density in lithium-treated patients with bipolar disorder. Biol Psychiatry 2007; 62: 7–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bruno SD, Barker GJ, Cercignani M, Symms M, Ron MA . A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry. Brain 2004; 127: 2433–2440.

    Article  CAS  PubMed  Google Scholar 

  103. McDonald C, Bullmore ET, Sham PC, Chitnis X, Suckling J, MacCabe J et al. Regional volume deviations of brain structure in schizophrenia and psychotic bipolar disorder: computational morphometry study. Br J Psychiatry 2005; 186: 369–377.

    Article  PubMed  Google Scholar 

  104. Chuang DM, Manji HK . In search of the Holy Grail for the treatment of neurodegenerative disorders: has a simple cation been overlooked? Biol Psychiatry 2007; 62: 4–6.

    Article  PubMed  PubMed Central  Google Scholar 

  105. 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.

    Article  CAS  PubMed  Google Scholar 

  106. Bearden CE, Thompson PM, Dutton RA, Frey BN, Peluso MAM, Nicoletti MA et al. Three-dimensional mapping of hippocampal anatomy in unmedicated and lithium-treated patients with bipolar disorder. Neuropsychopharmacology 2007; 33: 1229–1238.

    Article  PubMed  CAS  Google Scholar 

  107. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK . Lithium-induced increase in human brain grey matter. Lancet 2000; 356: 1241–1242.

    Article  CAS  PubMed  Google Scholar 

  108. Yucel K, McKinnon MC, Taylor VH, Macdonald K, Alda M, Young LT et al. Bilateral hippocampal volume increases after long-term lithium treatment in patients with bipolar disorder: a longitudinal MRI study. Psychopharmacology 2007; 195: 357–367.

    Article  CAS  PubMed  Google Scholar 

  109. Yucel K, Taylor VH, McKinnon MC, Macdonald K, Alda M, Young LT et al. Bilateral hippocampal volume increase in patients with bipolar disorder and short-term lithium treatment. Neuropsychopharmacology 2008; 33: 361–367.

    Article  CAS  PubMed  Google Scholar 

  110. Foland LC, Altshuler LL, Sugar CA, Lee AD, Leow AD, Townsend J et al. Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium. NeuroReport 2008; 19: 221–224.

    Article  PubMed  PubMed Central  Google Scholar 

  111. Monkul ES, Matsuo K, Nicoletti MA, Dierschke N, Hatch JP, Dalwani M et al. Prefrontal gray matter increases in healthy individuals after lithium treatment: a voxel-based morphometry study. Neurosci Lett 2007; 429: 7–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Atmaca M, Ozdemir H, Cetinkaya S, Parmaksiz S, Belli H, Poyraz AK et al. Cingulate gyrus volumetry in drug free bipolar patients and patients treated with valproate or valproate and quetiapine. J Psychiatr Res 2007; 41: 821–827.

    Article  PubMed  Google Scholar 

  113. 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.

    Article  CAS  PubMed  Google Scholar 

  114. Ahn KH, Lyoo IK, Lee HK, Song IC, Oh JS, Hwang J et al. White matter hyperintensities in subjects with bipolar disorder. Psychiatry Clin Neurosci 2004; 58: 516–521.

    Article  PubMed  Google Scholar 

  115. Pillai JJ, Friedman L, Stuve TA, Trinidad S, Jesberger JA, Lewin JS et al. Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder. Psychiatry Res 2002; 114: 51–56.

    Article  PubMed  Google Scholar 

  116. Beyer JL, Taylor WD, MacFall JR, Kuchibhatla M, Payne ME, Provenzale JM et al. Cortical white matter microstructural abnormalities in bipolar disorder. Neuropsychopharmacology 2005; 30: 2225–2229.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  118. Haznedar MM, Roversi F, Pallanti S, Baldini-Rossi N, Schnur DB, LiCalzi EM et al. Fronto-thalamo-striatal gray and white matter volumes and anisotropy of their connections in bipolar spectrum illnesses. Biol Psychiatry 2005; 57: 733–742.

    Article  PubMed  Google Scholar 

  119. 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.

    Article  PubMed  Google Scholar 

  120. Adler CM, Adams J, DelBello MP, Holland SK, Schmithorst V, Levine A et 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.

    Article  PubMed  Google Scholar 

  121. Davis KA, Kwon A, Cardenas VA, Deicken RF . Decreased cortical gray and cerebral white matter in male patients with familial bipolar 1 disorder. J Affect Disord 2004; 82: 475–485.

    PubMed  Google Scholar 

  122. El-Badri SM, Cousins DA, Parker S, Ashton HC, McAllister VL, Ferrier IN et al. Magnetic resonance imaging abnormalities in young euthymic patients with bipolar affective disorder. Br J Psychiatry 2006; 189: 81–82.

    Article  PubMed  Google Scholar 

  123. Houenou J, Wessa M, Douaud G, Leboyer M, Chanraud S, Perrin M et al. Increased white matter connectivity in euthymic bipolar disorder patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex. Mol Psychiatry 2007; 12: 1001–1010.

    Article  CAS  PubMed  Google Scholar 

  124. Ahearn EP, Steffens DC, Cassidy F, Van Meter SA, Provenzale JM, Seldin MF et al. Familial leukoencephalopathy in bipolar disorder. Am J Psychiatry 1998; 155: 1605–1607.

    Article  CAS  PubMed  Google Scholar 

  125. Kieseppa T, Van Erp TG, Haukka J, Partonen T, Cannon TD, Poutanen VP et al. Reduced left hemispheric white matter volume in twins with bipolar 1 disorder. Biol Psychiatry 2003; 54: 896–905.

    Article  PubMed  Google Scholar 

  126. McDonald C, Bullmore ET, Sham PC, Chitnis X, Wickham H, Bramon E et al. Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes. Arch Gen Psychiatry 2004; 61: 974–984.

    Article  PubMed  Google Scholar 

  127. Yildiz-Yesiloglu A, Ankerst DP . Neurochemical alterations of the brain in bipolar disorder and their implications for pathophysiology: a systematic review of the in vivo proton magnetic resonance spectroscopy findings. Prog Neuropsychopharmacol Biol Psychiatry 2006; 30: 969–995.

    Article  CAS  PubMed  Google Scholar 

  128. Stork C, Renshaw PF . Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry 2005; 10: 900–919.

    Article  CAS  PubMed  Google Scholar 

  129. Scherk H, Backens M, Schneider-Axmann T, Kemmer C, Usher J, Reith W et al. Neurochemical pathology in hippocampus in euthymic patients with bipolar 1 disorder. Acta Psychiatr Scand 2008; 117: 283–288.

    Article  CAS  PubMed  Google Scholar 

  130. Silverstone PH, Wu RH, O’Donnell T, Ulrich M, Asghar SJ, Hanstock CC . Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar disorder patients. Int Clin Psychopharmacol 2003; 18: 73–79.

    Article  PubMed  Google Scholar 

  131. Moore GJ, Bebchuk JM, Hasanat K, Chen G, Seraji-Bozorgzad N, Wilds IB et al. Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in support of bcl-2's neurotrophic effects. Biol Psychiatry 2000; 48: 1–8.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  133. Kato T, Hamakawa H, Shioiri T, Murashita J, Takahashi Y, Takahashi S et al. Choline-containing compounds detected by proton magnetic resonance spectroscopy in the basal ganglia in bipolar disorder. J Psychiatry Neurosci 1996; 21: 248–254.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Colla M, Schubert F, Bubner M, Heidenreich JO, Bajbouj M, Seifert F et al. Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol. Mol Psychiatry 2008. (e-pub ahead of print). doi: 10.1038/mp.2008.26.

    Article  PubMed  CAS  Google Scholar 

  135. Kato T, Takahashi S, Shioiri T, Murashita J, Hamakawa H, Inubushi T . Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 1994; 31: 125–133.

    Article  CAS  PubMed  Google Scholar 

  136. Atmaca M, Yildirim H, Ozdemir H, Ogur E, Tezcan E . Hippocampal 1H MRS in patients with bipolar disorder taking valproate versus valproate plus quetiapine. Psychol Med 2007; 37: 121–129.

    Article  PubMed  Google Scholar 

  137. Kato T, Takahashi S, Shioiri T, Inubushi T . Brain phosphorus metabolism in depressive disorders detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 1992; 26: 223–230.

    Article  CAS  PubMed  Google Scholar 

  138. Deicken RF, Weiner MW, Fein G . Decreased temporal lobe phosphomonoesters in bipolar diosrder. J Affect Disord 1995; 33: 195–199.

    Article  CAS  PubMed  Google Scholar 

  139. 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.

    Article  PubMed  Google Scholar 

  140. 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.

    Article  PubMed  Google Scholar 

  141. Phillips ML, Drevets WC, Rauch SL, Lane R . Neurobiology of emotion perception II: implications for major psychiatric disorders. Biol Psychiatry 2003; 54: 515–528.

    Article  PubMed  Google Scholar 

  142. Blumberg HP, Leung H-C, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC et al. A functional magnetic resonance imaging study of bipolar disorder. Arch Gen Psychiatry 2003; 60: 601–609.

    Article  PubMed  Google Scholar 

  143. 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.

    Article  PubMed  Google Scholar 

  144. Adler CM, Holland SK, Schmithorst V, Tuchfarber MJ, Strakowski SM . Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task. Bipolar Disord 2004; 6: 540–549.

    Article  PubMed  Google Scholar 

  145. Drapier D, Surguladze S, Marshall N, Schulze K, Fern A, Hall MH et al. Genetic liability for bipolar disorder is characterised by excess frontal activation in response to a working memory task. Biol Psychiatry 2008; 64: 513–520.

    Article  PubMed  Google Scholar 

  146. Chen G, Huang LD, Jiang YM, Manji HK . The mood stabilizing agent valproate inhibits the activity of glycogen synthase kinase 3. J Neurochem 1999b; 72: 1327–1330.

    Article  CAS  PubMed  Google Scholar 

  147. Du J, Quiroz J, Peixiong Y, Zarate C, Manji HK . Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking at synapses. Neuron Glia Biol 2004; 1: 231–243.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Lawrence NS, Williams AM, Surguladze S, Giampietro V, Brammer MJ, Andrew C 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.

    Article  PubMed  Google Scholar 

  149. Wessa M, Houenou J, Paillere-Martinot M-L, Berthoz S, Artiges E, Leboyer M et al. Fronto-striatal overactivation in euthymic bipolar patients during an emotional go/nogo task. Am J Psychiatry 2007; 164: 638–646.

    Article  PubMed  Google Scholar 

  150. Lagopoulos J, Ivanovski B, Malhi GS . An event-related functional MRI study of working memory in euthymic bipolar disorder. J Psychiatry Neurosci 2007; 32: 174–184.

    PubMed  PubMed Central  Google Scholar 

  151. Einat H, Yuan P, Gould TD, Li J, Du JH, Zhang L et al. The role of the extracellular signal-regulated kinase signalling pathway in mood modulation. J Neurosci 2003; 23: 7311–7316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Regenold WT . Lithium and increased cortical gray matter–more tissue or more water? Biol Psychiatry 2008; 63: e17.

    Article  PubMed  Google Scholar 

  153. Port JD, Unal SS, Mrazek DA, Marcus SM . Metabolic alterations in medication-free patients with bipolar disorder: a 3T CSF-corrected magnetic resonance spectroscopy imaging study. Psychiatry Res 2008; 162: 113–121.

    Article  CAS  PubMed  Google Scholar 

  154. Deicken RF, Fein G, Weiner MW . Abnormal frontal lobe phosphorus metabolism in bipolar disorder. Am J Psychiatry 1995; 152: 915–918.

    Article  CAS  PubMed  Google Scholar 

  155. Yildiz A, Sachs GS, Dorer DJ, Renshaw PF . 31P nuclear magnetic resonance spectroscopy findings in bipolar illness: a meta-analysis. Psychiatry Res 2001; 106: 181–191.

    Article  CAS  PubMed  Google Scholar 

  156. 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.

    Article  CAS  PubMed  Google Scholar 

  157. 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 

  158. Deckersbach T, Dougherty DD, Savage C, McMurrich S, Fischman AJ, Nierenberg A et al. Impaired recruitment of the dorsolateral prefrontal cortex and hippocampus during encoding in bipolar disorder. Biol Psychiatry 2006; 59: 138–146.

    Article  PubMed  Google Scholar 

  159. Culha AF, Osman O, Dogangun Y, Filiz K, Suna K, Kalkan ON et al. Changes in regional cerebral blood flow demonstrated by (99 m) Tc-HMPAO SPECT in euthymic patients. Eur Arch Psychiatry Clin Neurosci 2008; 258: 144–151.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  161. Strakowski SM, Adler CM, Holland SK, Mills NP, DelBello MP . A preliminary fMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology 2004; 29: 1734–1740.

    Article  PubMed  Google Scholar 

  162. Monks PJ, Thompson JM, Bullmore ET, Suckling J, Brammer MJ, Williams SC 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.

    Article  PubMed  Google Scholar 

  163. Curtis VA, Thompson JM, Seal ML, Monks PJ, Lloyd AJ, Harrison L et al. The nature of abnormal language processing in euthymic bipolar I disorder: evidence for a relationship between task demand and prefrontal function. Bipolar Disord 2007; 9: 358–369.

    Article  PubMed  Google Scholar 

  164. Malhi GS, Lagopoulos J, Sachdev P, Ivanovski B, Shnier R . An emotional Stroop functional MRI study of euthymic bipolar disorder. Bipolar Disord 2005; 7 (Suppl 5): 58–69.

    Article  PubMed  Google Scholar 

  165. Malhi GS, Lagopoulos J, Sachdev PS, Shnier R, Ketter T . Is a lack of disgust something to fear? A functional magnetic resonance imaging facial emotional recognition study in euthymic bipolar disorder patients. Bipolar Disord 2007; 9: 345–357.

    Article  PubMed  Google Scholar 

  166. 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.

    Article  PubMed  Google Scholar 

  167. Phillips ML, Ladouceur CD, Drevets WC . Neural systems underlying voluntary and automatic emotion regulation: toward a neural model of bipolar disorder. Mol Psychiatry 2008; 13: 829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Gitlin MJ, Swendsen J, Heller TL, Hammen C . Relapse and impairment in bipolar disorder. Am J Psychiatry 1995; 152: 1635–1640.

    Article  CAS  PubMed  Google Scholar 

  169. Chen G, Zeng WZ, Jiang L, Yuan PX, Zhao J, Manji HK . The mood stabilizing agents lithium and valproate robustly increase the expression of the neuroprotective protein bcl-2 in the CNS. J Neurochem 1999; 72: 879–882.

    Article  CAS  PubMed  Google Scholar 

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    C Langan & C McDonald

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Langan, C., McDonald, C. Neurobiological trait abnormalities in bipolar disorder. Mol Psychiatry 14, 833–846 (2009). https://doi.org/10.1038/mp.2009.39

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