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Can brain-imaging studies provide a ‘mood stabilizer signature?’

Molecular Psychiatry volume 7, pages S64–S70 (2002)Cite this article

Abstract

Brain-imaging investigations have attempted to characterize the neurobiological basis of bipolar disorder. Preliminary studies have also focused on in vivo brain correlates of treatment response with antidepressants, mood stabilizers and other psychotropic medications. A MEDLINE® literature search was conducted dating back to 1966. Selected in vivo brain-imaging studies that examined neurobiological correlates of treatment response in mood disorder patients were identified. Discrete anatomical abnormalities in subregions of the prefrontal cortex, medial temporal lobe and cerebellum have been identified in bipolar patients. Functional imaging studies suggested abnormalities in particular brain circuits encompassing these same brain regions and the striatum. However, functional imaging correlates of treatment response with lithium or other mood stabilizers have not yet been characterized. Neurochemical studies suggested a reduction in N-acetyl aspartate levels in prefrontal cortex and abnormalities in membrane phospholipids in frontal and temporal lobes. Preliminary findings suggest that lithium may increase the gray matter content and N-acetyl aspartate levels in various cortical regions, which could reflect its putative neurotrophic effects. Few in vivo receptor-imaging studies have examined brain correlates of treatment response in bipolar patients. The available studies suggest anatomical, neurochemical and functional brain abnormalities in bipolar patients. However, in vivo brain correlates of treatment response with mood stabilizers in bipolar patients have not yet been well characterized.

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References

  1. Soares JC, Innis RB . Brain imaging findings in bipolar disorder. In: Soares JC, Gershon S (eds) Basic Mechanisms and Therapeutic Implications of Bipolar Disorder Marcel Dekker: New York 2000 227–252

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. Soares JC, Mann JJ . The functional neuroanatomy of mood disorders J Psychiatr Res 1997 31: 393–432

    Article  CAS  PubMed  Google Scholar 

  5. Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL et al. Cingulate function in depression: a potential predictor of treatment response Neuroreport 1997 8: 1057–1061

    Article  CAS  PubMed  Google Scholar 

  6. 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 

  7. Sax KW, Strakowski SM, Zimmerman ME, DelBello MP, Keck PE Jr, Hawkins JM . Frontosubcortical neuroanatomy and the continuous performance test in mania Am J Psychiatry 1999 156: 139–141

    Article  CAS  PubMed  Google Scholar 

  8. 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  Google Scholar 

  9. 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 

  10. 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rajkowska G, Halaris A, Selemon LD . Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder Biol Psychiatry 2001 49: 741–752

    Article  CAS  PubMed  Google Scholar 

  12. Figueroa R, Harenski K, Nicoletti M, Brambilla P, Mallinger AG, Frank E et al. Dorsolateral prefrontal cortex abnormalities in bipolar disorder: possible effects of lithium treatment? Biol Psychiatry 2000 47: 103S–104S (abstr)

    Article  Google Scholar 

  13. 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 (letter) Arch Gen Psychiatry 1998 55: 663–664

    CAS  PubMed  Google Scholar 

  14. 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

    Article  CAS  PubMed  Google Scholar 

  15. Brambilla P, Harenski K, Nicoletti M, Sassi RB, Mallinger AG, Frank E et al. Are amygdala values increased in bipolar disorder patients? Bipolar Disord 2001 3: 28 (abstr)

    Google Scholar 

  16. Swayze VW 2nd, 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 

  17. Hauser P, Altshuler LL, Berrettini W, Dauphinais ID, Gelernter J, Post RM . Temporal lobe measurement in primary affective disorder by magnetic resonance imaging J Neuropsychiatry Clin Neurosci 1989 1: 128–134

    Article  CAS  PubMed  Google Scholar 

  18. 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 2001 106: 65–80

    Article  CAS  PubMed  Google Scholar 

  19. 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

    Article  CAS  PubMed  Google Scholar 

  20. 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 

  21. 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

    Article  CAS  PubMed  Google Scholar 

  22. Mayberg HS, Lewis PJ, Regenold W, Wagner HN Jr . Paralimbic hypoperfusion in unipolar depression J Nucl Med 1994 35: 929–934

    CAS  PubMed  Google Scholar 

  23. Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S et al. Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response Biol Psychiatry 2000 48: 830–843

    Article  CAS  PubMed  Google Scholar 

  24. Dolan RJ, Bench CJ, Brown RG, Scott LC, Frackowiak RS . Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow Psychol Med 1994 24: 849–857

    Article  CAS  PubMed  Google Scholar 

  25. George MS, Ketter TA, Parekh PI, Rosinsky N, Ring HA, Pazzaglia PJ et al. Blunted left cingulate activation in mood disorder subjects during a response interference task (the Stroop) J Neuropsychiatry Clin Neurosci 1997 9: 55–63

    Article  CAS  PubMed  Google Scholar 

  26. 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 

  27. Drevets WC, Videen TO, Price JL, Preskorn SH, Carmichael ST, Raichle ME . A functional anatomical study of unipolar depression J Neurosci 1992 12: 3628–3641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Soares JC, Krishnan KRR, Keshavan MS . Nuclear magnetic resonance spectroscopy—new insights into the pathophysiology of mood disorders Depression 1996 4: 14–30

    Article  CAS  PubMed  Google Scholar 

  29. Winsberg ME, Sachs N, Tate DL, Adalsteinsson E, Spielman D, Ketter TA . Decreased dorsolateral prefrontal N-acetyl aspartate in bipolar disorder Biol Psychiatry 2000 47: 475–481

    Article  CAS  PubMed  Google Scholar 

  30. Ende G, Braus DF, Walter S, Weber-Fahr W, Soher B, Maudsley AA et al. Effects of age, medication, and illness duration on the N-acetyl aspartate signal of the anterior cingulate region in schizophrenia Schizophr Res 2000 41: 389–395

    Article  CAS  PubMed  Google Scholar 

  31. Lindquist DM, Hawk RM, Karson CN, Komoroski RA . Effects of antipsychotic drugs on metabolite ratios in rat brain in vivo Magn Reson Med 2000 43: 355–358

    Article  CAS  PubMed  Google Scholar 

  32. Moore CM, Breeze JL, Gruber SA, Babb SM, Frederick BB, Villafuerte RA et al. Choline, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex Bipolar Disord 2000 2: 207–216

    Article  CAS  PubMed  Google Scholar 

  33. Steingard RJ, Yurgelun-Todd DA, Hennen J, Moore JC, Moore CM, Vakili K et al. Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy Biol Psychiatry 2000 48: 1053–1061

    Article  CAS  PubMed  Google Scholar 

  34. Renshaw PF, Lafer B, Babb SM, Fava M, Stoll AL, 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

    Article  CAS  PubMed  Google Scholar 

  35. Brambilla P, Stanley JA, Harenski K, Nicoletti M, Mallinger AG, Frank E et al. Glutamatertic abnormalities in the left dorso-lateral prefrontal cortex in unmedicated unipolar disorder patients: a preliminary study (abstract) Bipolar Disord 2001 3: 28

    Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA et al. Reduced cortical gamma-aminobutyric acid levels in depressed patients determined by proton magnetic resonance spectroscopy Arch Gen Psychiatry 1999 56: 1043–1047

    Article  CAS  PubMed  Google Scholar 

  38. Moore GJ, Bebchuk JM, Parrish JK, Faulk MW, Arfken CL, 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 

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

    Article  CAS  PubMed  Google Scholar 

  40. Kato T, Takahashi S, Shioiri T, Inubushi T . Alterations in brain phosphorous metabolism in bipolar disorder detected by in vivo 31P and 7Li magnetic resonance spectroscopy J Affect Disord 1993 27: 53–59

    Article  CAS  PubMed  Google Scholar 

  41. Kato T, Shioiri T, Murashita J, Hamakawa H, Inubushi T, Takahashi S . Phosphorus-31 magnetic resonance spectroscopy and ventricular enlargement in bipolar disorder Psychiatry Res 1994 55: 41–50

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  44. Kato T, Murashita J, Kamiya A, Shioiri T, Kato N, Inubushi T . Decreased brain intracellular pH measured by 31P-MRS in bipolar disorder: a confirmation in drug-free patients and correlation with white matter hyperintensity Eur Arch Psychiatry Clin Neurosci 1998 248: 301–306

    Article  CAS  PubMed  Google Scholar 

  45. Soares JC, Boada F, Keshavan MS . Brain lithium measurements with 7Li magnetic resonance spectroscopy (MRS): a literature review Eur Neuropsychopharmacol 2000 10: 151–158

    Article  CAS  PubMed  Google Scholar 

  46. Renshaw PF, Wicklund S . In vivo measurement of lithium in humans by nuclear magnetic resonance spectroscopy Biol Psychiatry 1988 23: 465–475

    Article  CAS  PubMed  Google Scholar 

  47. Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L et al. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography Biol Psychiatry 1998 44: 1090–1098

    Article  CAS  PubMed  Google Scholar 

  48. Massou JM, Trichard C, Attar-Levy D, Feline A, Corruble E, Beaufils B et al. Frontal 5-HT2A receptors studied in depressive patients during chronic treatment by selective serotonin reuptake inhibitors Psychopharmacol (Berl) 1997 133: 99–101

    Article  CAS  Google Scholar 

  49. Attar-Levy D, Martinot JL, Blin J, Dao-Castellana MH, Crouzel C, Mazoyer B et al. The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine Biol Psychiatry 1999 45: 180–186

    Article  CAS  PubMed  Google Scholar 

  50. Meyer JH, Kapur S, Houle S, DaSilva J, Owczarek B, Brown GM et al. Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging study Am J Psychiatry 1999 156: 1029–1034

    CAS  PubMed  Google Scholar 

  51. Yatham LN, Liddle PF, Shiah IS, Scarrow G, Lam RW, Adam MJ et al. Brain serotonin2 receptors in major depression: a positron emission tomography study Arch Gen Psychiatry 2000 57: 850–858

    Article  CAS  PubMed  Google Scholar 

  52. Biver F, Wikler D, Lotstra F, Damhaut P, Goldman S, Mendlewicz J . Serotonin 5-HT2 receptor imaging in major depression: focal changes in orbito-insular cortex Br J Psychiatry 1997 171: 444–448

    Article  CAS  PubMed  Google Scholar 

  53. Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ et al. PET imaging of serotonin1A receptor binding in depression Biol Psychiatry 1999 46: 1375–1387

    Article  CAS  PubMed  Google Scholar 

  54. Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J et al. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment Arch Gen Psychiatry 2000 57: 174–180

    Article  CAS  PubMed  Google Scholar 

  55. 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

    Article  CAS  PubMed  Google Scholar 

  56. 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

    Article  CAS  PubMed  Google Scholar 

  57. Soares JC, Innis RB . Neurochemical brain imaging investigations of schizophrenia Biol Psychiatry 1999 46: 600–615

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    J C Soares

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Soares, J. Can brain-imaging studies provide a ‘mood stabilizer signature?’. Mol Psychiatry 7 (Suppl 1), S64–S70 (2002). https://doi.org/10.1038/sj.mp.4001020

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