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Mood disorders – review of structural MRI studies

Published online by Cambridge University Press:  24 June 2014

E. Serap Monkul
Affiliation:
Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA South Texas VA Health Care System, Audie L. Murphy Division, San Antonio, TX, USA Department of Psychiatry, Dokuz Eylül University School of Medicine, Izmir, Turkey
Gin S. Malhi
Affiliation:
Mood Disorders Unit, The University of New South Wales, Sydney, Australia
Jair C. Soares*
Affiliation:
Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA South Texas VA Health Care System, Audie L. Murphy Division, San Antonio, TX, USA Department of Radiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
*
Jair C. Soares MD, Division of Mood and Anxiety Disorders, Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA. Tel: (210) 567-5492; Fax: (210) 567-3759; E-mail: soares@uthscsa.edu

Abstract

Background:

Mood disorders are related to considerable morbidity and mortality, and although there is little doubt that they are brain-based disorders, their neural correlates still remain elusive. A neuro-anatomic model of mood regulation comprising the prefrontal cortex, amygdala-hippocampus complex, thalamus, basal ganglia, and connections among these areas has been proposed.

Objective:

We reviewed the evidence for regional brain abnormalities in bipolar disorder, and attempted to integrate available findings into a comprehensive pathophysiological model of illness.

Methods:

A computerized Medline Ovid search was conducted for the period 1966–2002, and complemented by a manual search of bibliographical references from recent reviews. Articles meeting specified criteria were included.

Results:

Hyperintense lesions in cortical and subcortical regions are the most consistently reported and widely studied structural abnormalities. Smaller prefrontal cortical volume is a common finding in bipolar disorder and unipolar depression. Enlarged amygdala (in bipolar disorder) and smaller hippocampus (in unipolar depression) have been reported by several groups. Decreased volumes (in unipolar depression) and increased or unaltered volumes (in bipolar disorder) of striatal structures have been reported.

Conclusions:

Bipolar and unipolar mood disorders are associated with detectable structural brain abnormalities. The histopathology underlying such anatomical changes remains to be elucidated. To reach more definitive conclusions about neuroanatomical changes that take place during the course of mood disorders, prospective longitudinal studies are needed. Also, integration with functional imaging is necessary in order to elucidate the relevance of identified structural abnormalities.

Type
Research Article
Copyright
Copyright © 2003 Blackwell Munksgaard

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References

Strakowski, SM, Del Bello, MP, Adler, C, Cecil, DM, Sax, KW. Neuroimaging in bipolar disorder. Bipolar Disord 2000;2: 148164.Google Scholar
Soares, JC, Mann, JJ. The functional neuroanatomy of mood disorders. J Psychiatric Res 1997;31: 393432. Google Scholar
Berton, GG, Torello, MW. The paleocerebellum and the integration of behavioral function. Physiol Psychol 1982;10: 112. Google Scholar
Krishnan, KRR, MacFall, JR. Basic principles of magnetic resonance imaging. In: Krishnan, KRR, Doraiswamy, PM, eds. Brain Imaging in Clinical Psychiatry. New York: Marcell-Dekker, 1997: 112. Google Scholar
Rangel-Guerra, RA, Perez-Payan, H, Minkoff, L, Todd, LE. Nuclear magnetic resonance in bipolar affective disorder. AJNR Am J Neuroradiol 1983;4: 229231.Google Scholar
Soares, JC, Mann, JJ. The anatomy of mood disorders –review of structural neuroimaging studies. Biol Psychiatry 1997;41: 86106.Google Scholar
Strakowski, SM, Adler, CMI, Del Bello, MP. Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder? Bipolar Disord 2002;4: 8088.Google Scholar
Bearden, CE, Hoffman, KM, Cannon, TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord 2001;3: 106150.Google Scholar
Strakowski, SM, Wilson, DR, Tohen, M, Woods, BT, Douglass, AW, Stoll, AL. Structural brain abnormalities in first-episode mania. Biol Psychiatry 1993;33: 602609.Google Scholar
Jurjus, GJ, Nasrallah, HA, Brogan, M, Olson, SC. Developmental brain anomalies in schizophrenia and bipolar disorder: a controlled MRI study. J Neuropsychiatry Clin Neurosci 1993;5: 375378.Google Scholar
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: 4150.Google Scholar
Friedman, L, Findling, RL, Kenny, JTet al. An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects. Biol Psychiatry 1999;46: 7888.Google Scholar
Zipursky, RB, Seeman, MV, Bury, A, Langevin, R, Wortzman, G, Katz, R. Deficits in gray matter volume are present in schizophrenia but not bipolar disorder. Schizophr Res 1997;26: 8592.Google Scholar
Swayze, VW, Andreasen, NC, Alliger, RJ, Ehrhardt, JC, Yuh, WT. Structural brain abnormalities in bipolar affective disorder. Ventricular enlargement and focal signal hyperintensities. Arch General Psychiatry 1990;47: 10541059. Google Scholar
Lim, KO, Rosenbloom, MJ, Faustman, WO, Sullivan, EV, Pfefferbaum, A. Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res 1999;40: 219227.Google Scholar
Botteron, KN, Vannier, MW, Geller, B, Todd, RD, Lee, BC. Preliminary study of magnetic resonance imaging characteristics in 8- to 16-year-olds with mania. J Am Acad Child Adolesc Psychiatry 1995;34: 742749.Google Scholar
Dupont, RM, Jernigan, TL, Gillin, JC, Butters, N, Delis, DC, Hesselink, JR. Subcortical signal hyperintensities in bipolar patients detected by MRI. Psychiatry Res 1987;21: 357358.Google Scholar
Johnstone, EC, Owens, DG, Crow, TJet al. Temporal lobe structure as determined by nuclear magnetic resonance in schizophrenia and bipolar affective disorder. J Neurol Neurosurg Psychiatry 1989;52: 736741.Google Scholar
Lesser, IM, Miller, BL, Boone, KBet al. Brain injury and cognitive function in late-onset psychotic depression. J Neuropsychiatry Clin Neurosci 1991;3: 3340.Google Scholar
Risch, SC, Lewine, RJ, Kalin, Nhet al. Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia. Neuropsychopharmacology 1992;6: 95100.Google Scholar
Shah, SA, Doraiswamy, PM, Husain, MMet al. Posterior fossa abnormalities in major depression: a controlled magnetic resonance imaging study. Acta Psychiatr Scand 1992;85: 474479.Google Scholar
Greenwald, BS, Kramer-Ginsberg, E, Bogerts, Bet al. Qualitative magnetic resonance imaging findings in geriatric depression. Possible link between later-onset depression and Alzheimer's disease? Psychol Med 1997;27: 421431.Google Scholar
Coffey, CE, Wilkinson, WE, Weiner, RDet al. Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Arch General Psychiatry 1993;50: 716. Google Scholar
Rabins, PV, Pearlson, GD, Aylward, E, Kumar, AJ, Dowell, K. Cortical magnetic resonance imaging changes in elderly inpatients with major depression. Am J Psychiatry 1991;148: 617620.Google Scholar
Iidaka, T, Nakajima, T, Kawamoto, Ket al. Signal hyperintensities on brain magnetic resonance imaging in elderly depressed patients. Eur Neurol 1996;36: 293299.Google Scholar
Dahabra, S, Ashton, Ch, Bahrainian, Met al. Structural and functional abnormalities in elderly patients clinically recovered from early- and late-onset depression. Biol Psychiatry 1998;44: 3446.Google Scholar
Hauser, P, Matochik, J, Altshuler, LLet al. MRI-based measurements of temporal lobe and ventricular structures in patients with bipolar I and bipolar II disorders. J Affect Disord 2000;60: 2532.Google Scholar
Elkis, H, Friedman, L, Wise, A, Meltzer, HY. Meta-analyses of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Comparisons with controls or patients with schizophrenia. Arch General Psychiatry 1995;52: 735746. Google Scholar
Kumar, A, Miller, D, Ewbank, Det al. Quantitative anatomic measures and comorbid medical illness in late-life major depression. Am J Geriatr Psychiatry 1997;5: 1525.Google Scholar
Pantel, J, Schroder, J, Essig, Met al. Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia. J Affect Disord 1997;42: 6983.Google Scholar
Harvey, I, Persaud, R, Ron, MA, Baker, G, Murray, RM. Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls. Psychol Med 1994;24: 689699.Google Scholar
Zubenko, GS, Sullivan, P, Nelson, JP, Belle, Sh, Huff, J, Wolf, GL. Brain imaging abnormalities in mental disorders of late life. Arch Neurol 1990;47: 11071111.Google Scholar
Lammers, GS, Doraiswamy, PM, Husain, MMet al. MRJ of the corpus callosum and septum pellucidum in depression. Biol Psychiatry 1991;29: 295308.Google Scholar
Krishnan, KR. Neuroanatomical substrates of depression in the elderly. J Geriatr Psychiatry Neurol 1993;6: 3958.Google Scholar
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: 663664.Google Scholar
Aylward, EH, Roberts-Twillie, JV, Barta, PEet al. Basal ganglia volumes and white matter hyperintensities in patients with bipolar disorder. Am J Psychiatry 1994;151: 687693.Google Scholar
DelBello, MP, Strakowski, SM, Zimmerman, ME, Hawkins, JM, Sax, KW. MRI analysis of the cerebellum in bipolar disorder: a pilot study. Neuropsychopharmacology 1999;21: 6368.Google Scholar
Dupont, RM, Jernigan, TL, Heindel, Wet al. Magnetic resonance imaging and mood disorders. Localization of white matter and other subcortical abnormalities. Arch Gen Psychiatry 1995;52: 747755.Google Scholar
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: 482486.Google Scholar
Pearlson, GD, Barta, PE, Powers, RE. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry 1997;41: 14.Google Scholar
Roy, PD, Zipursky, RB, Saint-Cyr, JA, Bury, A, Langevin, R, Seeman, MV. Temporal horn enlargement is present in schizophrenia and bipolar disorder. Biol Psychiatry 1998;44: 418422.Google Scholar
Sax, KW, Strakowski, SM, Zimmerman, ME, Del Bello, MP, Keck, PE JR, , Hawkins, JM. Frontosubcortical neuroanatomy and the continuous performance test in mania. Am J Psychiatry 1999;156: 139141.Google Scholar
Schlaepfer, TE, Harris, GJ, Tien, AYet al. Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 1994;151: 842848.Google Scholar
Strakowski, SM, Del Bello, MP, Sax, KWet al. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999;56: 254260.Google Scholar
Woods, BT, Yurgelun-Todd, D, Mikulis, D, Pillay, SS. Age-related MRI abnormalities in bipolar illness: a clinical study. Biol Psychiatry 1995;38: 846847.Google Scholar
Hoge, EA, Friedman, L, Schulz, SC. Meta-analysis of brain size in bipolar disorder. Schizophr Res 1999;37: 177181.Google Scholar
Axelson, DA, Doraiswamy, PM, McDonald, WMet al. Hypercotisolemia and hippocampal changes in depression. Psychiatry Res 1993;47: 163173.Google Scholar
Coffey, CE, Wilkinson, WE, Weiner, RDet al. The dexamethasone suppression test and quantitative cerebral anatomy in depression. Biol Psychiatry 1993;33: 442449.Google Scholar
Husain, MM, McDonald, WM, Doraiswamy, PMet al. A magnetic resonance imaging study of putamen nuclei in major depression. Psychiatry Res 1991;40: 9599.Google Scholar
Kumar, A, Bilker, W, Jin, J, Udupa, J. Atrophy and high intensity lesions: complementary neurobiological mechanisms in late-life major depression. Neuropsychopharmacology 2000;22: 264272.Google Scholar
Krishnan, KRR, McDonald, WM, Escalona, PRet al. Magnetic resonance imaging of the caudate nuclei in depression: preliminary observations. Arch Gen Psychiatry 1992;49: 553557.Google Scholar
Brambilla, P, Harenski, K, Nicoletti, Met al. Differential effects on brain gray matter in bipolar patients and healthy individuals. Neuropsychobiology 2001; 43: 242247.Google Scholar
Moore, GJ, Bebchuk, JM, Wilds, IB, Chen, G, Manji, HK, Menji, HK. Lithium-induced increase in human brain grey matter. Lancet 2000;356: 12411242.Google Scholar
Sassi, RB, Nicoletti, M, Brambilla, Pet al. Increased gray matter Volume in lithium-treated bipolar disorder patients. Neurosci Lett 2002;329: 243245.Google Scholar
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: 11391144.Google Scholar
Dupont, RM, Jernigan, TL, Butters, Net al. Subcortical abnormalities detected in bipolar affective disorder using magnetic resonance imaging: clinical and neuropsychological significance [see comments]. Arch Gen Psychiatry 1990;47: 5559.Google Scholar
Figiel, GS, Krishnan, KR, Rao, VPet al. Subcortical hyperintensities on brain magnetic resonance imaging: a comparison of normal and bipolar subjects. J Neuropsychiatry Clin Neurosci 1991;3: 1822.Google Scholar
McDonald, WM, Krishnan, KR, Doraiswamy, PM, Blazer, DG. Occurrence of subcortical hyperintensities in elderly subjects with mania. Psychiatry Res 1991;40: 211220.Google Scholar
McDonald, WM, Tupler, LA, Marsteller, FAet al. Hyperintense lesions on magnetic resonance images in bipolar disorder. Biol Psychiatry 1999;45: 965971.Google Scholar
Moore, PB, El-Badri, SM, Cousins, Det al. White matter lesions and season of birth of patients with bipolar affective disorder. Am J Psychiatry 2001;158: 15211524.Google Scholar
Strakowski, SM, Woods, BT, Tohen, M, Wilson, DR, Douglass, AW, Stoll, AL. MRI subcortical signal hyperintensities in mania at first hospitalization. Biol Psychiatry 1993;33: 204206.Google Scholar
Brown, FW, Lewine, RJ, Hudgins, PA, Risch, SC. White matter hyperintensity signals in psychiatric and nonpsychiatric subjects. Am J Psychiatry 1992;149: 620625.Google Scholar
Krabbendam, L, Honig, A, Wiersma, Jet al. Cognitive dysfunctions and white matter lesions in patients with bipolar disorder in remission. Acta Psychiatr Scand 2000;101: 274280.Google Scholar
Persaud, R, Russow, H, Harvey, Iet al. Focal signal hyperintensities in schizophrenia. Schizophr Res 1997; 27: 5564.Google Scholar
Moore, PB, Shepherd, DJ, Eccleston, Det al. Cerebral white matter lesions in bipolar affective disorder: relationship to outcome. Br J Psychiatry 2001;178: 172176.Google Scholar
Pillai, JJ, Friedman, L, Stuve, TAet al. Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder. Psychiatr Res 2002;114: 5156. Google Scholar
Lyoo, IK, Lee, HK, Jung, JH, Noam, GG, Renshaw, PF. White matter hyperintensities on magnetic resonance imaging of the brain in children with psychiatric disorders. Compr Psychiatry 2002;43: 361368.Google Scholar
Videbech, P. MRI findings in patients with affective disorder: a meta-analysis. Acta Psychiatr Scand 1997;96: 157168.Google Scholar
Kumar, A, Mintz, J, Bilker, W, Gottlieb, G. Autonomous neurobiological pathways to late-life major depressive disorder: clinical and pathophysiological implications. Neuropsychopharmacology 2002;26: 229236.Google Scholar
Cummings, JL. Frontal-subcortical circuits and human behavior. Hum Behav Arch Neurol 1993;50: 873880. Google Scholar
Coffman, JA, Bornstein, RA, Olson, SC, Schwarzkopf, SB, Nasrallah, HA. Cognitive impairment and cerebral structure by MRI in bipolar disorder. Biol Psychiatry 1990;27: 11881196.Google Scholar
Drevets, WC, Price, JL, Simpson, JR Jret al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386: 824827.Google Scholar
Brambilla, P, Nicoletti, MA, Harenski, Ket al. Anatomical MRI study of subgenual prefrontal cortex in bipolar and unipolar subjects. Neuropsychopharmacology 2002; 27: 792799. Google Scholar
Lopez-Larson, MPI, Bello, MP, Zimmerman, ME, Schwiers, ML, Strakowski, SM. Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry 2002;52: 93100.Google Scholar
ÖNgür, D, Drevets, WC, Price, JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998;95: 1329013295.Google Scholar
Rajkowska, G, Halaris, A, Selemon, LD. Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 2001;49: 741752.Google Scholar
Kumar, A, Jin, Z, Bilker, W, Udupa, J, Gottlieb, G. Late-onset minor and major depression: early evidence for common neuroanatomical substrates detected by using MRI. Proc Natl Acad Sci USA 1998;95: 76547658.Google Scholar
Bremner, JD, Narayan, M, Anderson, ER, Staib, LH, Miller, HL, Charney, DS. Hippocampal Volume reduction in major depression. Am J Psychiatry 2000;157: 115118.Google Scholar
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: 128134.Google Scholar
Swayze, VWd, 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: 221240.Google Scholar
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: 147162.Google Scholar
Hirayasu, Y, McCarley, RW, Salisbury, DFet al. Planum temporale and Heschl gyrus volume reduction in schizophrenia: a magnetic resonance imaging study of first-episode patients. Arch Gen Psychiatry 2000;57: 692699.Google Scholar
Shah, PJ, Ebmeier, KP, Glabus, MF, Goodwin, GM. Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br J Psychiatry 1998; 172: 527532.Google Scholar
Sheline, YI, Sanghavi, M, Mintun, MA, Gado, Mh. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 1999;19: 50345043.Google Scholar
Caetano, SC, Sassi, R, Brambilla, Pet al. MRI study of thalamic volumes in bipolar and unipolar patients and healthy individuals. Psychiatry Res 2001;108: 161168.Google Scholar
Deicken, RF, Eliaz, Y, Feiwell, R, Schuff, N. Increased thalamic N-acetylaspartate in male patients with familial bipolar I disorder. Psychiatry Res 2001;106: 3545.Google Scholar
Ashtari, M, Greenwald, BS, Kramer-Ginsberg, Eet al. Hippocampal/amygdala volumes in geriatric depression. Psychol Med 1999;29: 629638.Google Scholar
Steffens, DC, Byrum, CE, McQuoid, DRet al. Hippocampal Volume in geriatric depression. Biol Psychiatry 2000;48: 301309.Google Scholar
Vakili, K, Pillay, SS, Lafer, Bet al. Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Biol Psychiatry 2000; 47: 10871090.Google Scholar
Mervaala, E, Fohr, J, Kononen, Met al. Quantitative MRI of the hippocampus and amygdala in severe depression. Psychol Med 2000;30: 117125.Google Scholar
Sheline, YI, Gado, Mh, Price, JL. Amygdala core nuclei Volumes are decreased in recurrent major depression. Neuroreport 1998;9: 20232028.Google Scholar
Parashos, IA, Tupler, LA, Blitchington, T, Krishnan, KR. Magnetic-resonance morphometry in patients with major depression. Psychiatry Res 1998;84: 715.Google Scholar
Pillay, S, Renshaw, P, Bonello, C, Lafer, B, Fava, M, Yurgelun-Todd, D. A quantitative magnetic resonance imaging study of caudate and lenticular nucleus gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity. Psychiatry Res: Neuroimaging 1998;84: 6174. Google Scholar
Lenze, EJ, Sheline, YI. Absence of striatal volume differences between depressed subjects with no comorbid medical illness and matched comparison subjects. Am J Psychiatry 1999;156: 19891991.Google Scholar
Brambilla, P, Harenski, K, Nicoletti, Met al. MRI study of posterior fossa structures and brain ventricles in bipolar patients. J Psychiatr Res 2001;35: 313322.Google Scholar
Escalona, PR, Early, B, McDonald, WMet al. Reduction of cerebellar volume in major depression: a controlled MRI study. Depression 1993;1: 156158. Google Scholar
Pillay, SS, Yurgelun-Todd, DA, Bonello, CM, Lafer, B, Fava, M, Renshaw, PF. A quantitative magnetic resonance imaging study of cerebral and cerebellar gray matter volume in primary unipolar major depression: relationship to treatment response and clinical severity. Biol Psychiatry 1997;42: 7984.Google Scholar
Hauser, P, Dauphinais, ID, Berrettini, W, Delisi, LE, Gelernter, J, Post, RM. Corpus callosum dimensions measured by magnetic resonance imaging in bipolar affective disorder and schizophrenia. Biol Psychiatry 1989;26: 659668.Google Scholar
Wu, JC, Buchsbaum, MS, Johnson, JCet al. Magnetic resonance and positron emission tomography imaging of the corpus callosum: size, shape and metabolic rate in unipolar depression. J Affect Disord 1993;28: 1525.Google Scholar
Brambilla, P, Nicoletti, M, Sassi, RBet al. MRI study of corpus callosum abnormalities in bipolar patients. Biol Psychiatry, in press. Google Scholar
Sassi, RB, Nicoletti, M, Brambilla, Pet al. Decreased pituitary volume in patients with bipolar disorder. Biol Psychiatry 2001;50: 271280.Google Scholar
Krishnan, KR, Doraiswamy, PM, Lurie, SNet al. Pituitary size in depression. J Clin Endocrinol Metab 1991;72: 256259.Google Scholar
Schwartz, PJ, Loe, JA, Bash, CNet al. Seasonality and pituitary volume. Psychiatry Res 1997;74: 151157.Google Scholar
Rybakowski, JK, Twardowska, K. The dexamethasone/corticotropin-releasing hormone test in depression in bipolar and unipolar affective illness. J Psychiatr Res 1999;33: 363370.Google Scholar
Lenox, Rh, Gould, TD, Manji, HK. Endophenotypes in bipolar disorder. Am J Med Genet 2002;114: 391406.Google Scholar