Hostname: page-component-77f85d65b8-lfk5g Total loading time: 0 Render date: 2026-04-18T13:03:16.713Z Has data issue: false hasContentIssue false
  • English
  • Français

The Neurophysiology of Childhood and Adolescent Bipolar Disorder

Published online by Cambridge University Press:  07 November 2014

Melissa P. DelBello ,
Caleb M. Adler  and
Stephen M. Strakowski
Get access Rights & Permissions [Opens in a new window]

Abstract

Introduction: Children and adolescents with bipolar disorder often present with higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder than adults with bipolar disorder. It is unclear whether the differences in clinical presentation between youth and adults with bipolar disorder are due to differences in underlying etiologies or developmental differences in symptom manifestation. Neuroimaging studies of children and adolescents with bipolar disorder may clarify whether neurobiological abnormalities associated with early-and adult-onset bipolar disorder are distinct. Moreover, children and adolescents with bipolar disorder are typically closer to their illness onset than bipolar adults, providing a window of opportunity for identifying core neurobiological characteristics of the illness (ie, disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course.

Methods: Peer-reviewed publications of neuroimaging studies of bipolar children and adolescents were reviewed.

Results: Structural, neurochemical, and neurofunctional abnormalities in prefrontal and medical temporal and subcortical limbic structures, including the striatum, amygdala, and possibly hippocampus, are present in children and adolescents with bipolar disorder.

Conclusion: Differences between neurobiological abnormalities in bipolar youth and adults as well as recommendations for future research directions are discussed.

Information

Type
Original Research
Information
CNS Spectrums , Volume 11 , Issue 4 , April 2006 , pp. 298 - 311
Copyright
Copyright © Cambridge University Press 2006

Access options

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

Article purchase

Temporarily unavailable

References

REFERENCES

1.Perlis, RH, Miyahara, S, Marangell, LB, et al.Long-Term implications of early onset in bipolar disorder: data from the first 1000 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD). Biol Psychiatry. 2004;55:875–881.Google Scholar
2.Lish, JD, Dime-Meenan, S, Whybrow, PC, Price, RA, Hirschfeld, RM. The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord. 1994;32:281–294.CrossRefGoogle Scholar
3.Geller, B, Luby, J. Child and adolescent bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 1997;37:1168–1176.Google Scholar
4.Pavuluri, MN, Birmaher, B, Naylor, MW. Pediatric bipolar disorder: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 2005;44(9):846–871.CrossRefGoogle ScholarPubMed
5.McElroy, SL, Strakowski, SM, West, SA, Keck, PE Jr, McConville, BJ. Phenomenology of adolescent and adult mania in hospitalized patients with bipolar disorder. Am J Psychiatry. 1997;254:44–49.Google Scholar
6.Adler, CM, Adams, J, DelBello, M, et al.Evidence of white matter pathology in first-episode manic adolescents with bipolar disorder: A diffusion tensor imaging study. Am J Psychiatry. 2006;163:322–324.Google Scholar
7.Botteron, KN, Figiel, GS, Wetzel, MW, Hudziak, J, VanEerdewegh, M. MRI abnormalities in adolescent bipolar affective disorder. J Am Acad Child Adolesc Psychiatry. 1992;31:258–261.Google Scholar
8.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;34:742–749.CrossRefGoogle ScholarPubMed
9.Blumberg, HP, Kaufman, J, Martin, A, et al.Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry. 2003;60:1201–1208.Google Scholar
10.Chang, K, Karchemskiy, A, Barnea-Goraly, N, Garrett, A, Simeonova, DI, Reiss, A. Reduced amygdalar gray matter volume in familial pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005;44:565–573.CrossRefGoogle ScholarPubMed
11.Chang, K, Barnea-Goraly, N, Karchemskiy, A, et al.Cortical magnetic resonance imaging findings in familial pediatric bipolar disorder. Biol Psychiatry. 2005;58:197–203.Google Scholar
12.Chen, BK, Sassi, R, Axelson, D, et al.Cross-section study of abnormal amygdala development in adolescents and young adults with bipolar disorder. Biol Psychiatry. 2004;56:399–405.CrossRefGoogle Scholar
13.Chen, HH, Nicoletti, M, Sanches, M, et al.Normal pituitary volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study. Depress Anxiety. 2004;20:182–186.Google Scholar
14.Chen, HH, Nicoletti, MA, Hatch, JP, et al.Abnormal left superior temporal gyrus volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study. Neurosci Lett. 2004;363:65–68.Google Scholar
15.Dasari, M, Friedman, L, Jesberger, J, et al.A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to health controls. Psychiatry Res. 1999;91:155–162.CrossRefGoogle ScholarPubMed
16.DelBello, MP, Zimmerman, ME, Mills, NP, Getz, GE, Strakowski, SM. Magnetic resonance imaging analysis of amygdale and other subcortical brain regions in adolescents with bipolar disorder. Bipolar Disord. 2004;6;143–152.Google Scholar
17.Dickstein, DP, Milham, MP, Nugent, AC, et al.Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. Arch Gen Psychiatry. 2005;62:734–741.CrossRefGoogle ScholarPubMed
18.Frazier, JA, Chiu, S, Breeze, JL, et al.Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. Am J Psychiatry. 2005;162:1256–1265.Google Scholar
19.Friedman, L, Findling, RL, Kenny, JT, et al.An MRI study of adolescent patients with either schizophrenia or bipolar disorder as compared to healthy control subjects. Biol Psychiatry. 1999;46:78–88.Google Scholar
20.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;43:361–368.CrossRefGoogle ScholarPubMed
21.Pillai, JJ, Friedman, L, Stuve, TA, et al.Increased presence of white matter hyperintensities in adolescent patients with bipolar disorder. Psychiatry Res. 2002;114:51–56.Google Scholar
22.Sanches, M, Sassi, RB, Axelson, D, et al.Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study. Psychiatry Res. 2005;138:43–49.Google Scholar
23.Sanches, M, Roberts, RL, Sassi, RB, et al.Developmental abnormalities in striatum in young bipolar patients: a preliminary study. Bipolar Disord. 2005;7:153–158.CrossRefGoogle ScholarPubMed
24.Wilke, M, Kowatch, RA, DelBello, MP, Mills, NP, Holland, SK. Voxel-based morphometry in adolescents with bipolar disorder: first results. Psychiatry Res. 2004;131:57–69.Google Scholar
25.Strakowski, SM, DelBello, MP, Adler, C, Cecil, DM, Sax, KW. Neuroimaging in bipolar disorder. Bipolar Disord. 2000;2(3 pt 1):148–164.CrossRefGoogle ScholarPubMed
26.Figiel, GS. Krishnan, KR, Rao, VP, et al.Subcortical hyperintensities on brain magnetic resonance imaging: a comparison of normal and bipolar subjects. J Neuropsychiatry Clin Neurosci. 1991;3:18–22.Google ScholarPubMed
27.Ahn, KH, Lyoo, IK, Lee, HK, et al.White matter hyperintensities in subjects with bipolar disorder. Psychiatry Clin Neurosci. 2004;58:516–521.CrossRefGoogle ScholarPubMed
28.Monkul, ES, Malhi, GS, Soares, JC. Anatomical MRI abnormalities in bipolar disorder: do they exist and do they progress? Aust N Z J Psychiatry. 2005;39:222–226.Google Scholar
29.Strakowski, SM, DelBello, MP, Adler, CM. The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Mol Psychiatry. 2005;10:106–116.CrossRefGoogle ScholarPubMed
30.Adleman, NE, Barnea-Giraky, N, Chang, KD. Review of magnetic resonance imaging and spectroscopy studies in children with bipolar disorder. Expert Rev Neurother. 2004;4:69–77.Google Scholar
31.Beaulieu, C. The basis of anisotropic water diffusion in the nervous system–a technical review. NMR Biomed. 2002;15:435–455.Google Scholar
32.Adler, CM, Holland, SK, Scmithorst, V, et al.Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study. Bipolar Disord. 2004;6:197–203.CrossRefGoogle ScholarPubMed
33.Strakowski, SM, DelBello, MPZimmerman, ME, et al.Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder. Am J Psychiatry. 2002;159:1841–1847.Google Scholar
34.Hoge, EA, Friedman, L, Schultz, SC. Meta-analysis of brain size in bipolar disorder. Schizophr Res. 1999;37:177–181.Google Scholar
35.Lim, KO, Rosenbloom, MJ, Faustman, WO, Sullivan, EV, Pfefferbaum, A. Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res. 1999;40:219–227.Google Scholar
36.Lopez-Larson, MP, DelBello, MP, Zimmerman, ME, Schwiers, ML, Strakowski, SM. Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biol Psychiatry. 2002;52:93–100.CrossRefGoogle ScholarPubMed
37.Frangou, S. The Maudsley Bipolar Disorder Project. Epilepsia. 2005;46:19–25.Google Scholar
38.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.Google Scholar
39.Soares, JC, Kochunov, PMonkul, ES, et al.Structural brain changes in bipolar disorder using deformation field morphometry. Neuroreport. 2005;16:541–544.Google Scholar
40.Phillips, ML, Drevets, WC, Rauch, SL, Lane, R. Neurobiology of emotion perception Il: Implications for major psychiatric disorders. Biol Psychiatry. 2003;54:515–528.CrossRefGoogle Scholar
41.Pearlson, GD, Barta, PE, Powers, RE, et al.Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry. 1997;41:1–14.CrossRefGoogle ScholarPubMed
42.Geller, B, Bolhofner, K, Craney, JL, Williams, M, DelBello, MP, Gundersen, K. Psychosocial functioning in a prepubertal and early adolescent bipolar disorder phenotype. J Am Acad Child Adolesc Psychiatry. 2000;39:1543–1548.Google Scholar
43.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 Gen Psychiatry. 1995;52:735–746.Google Scholar
44.Strakowski, SM, DelBello, MP, Sax, KW, et al.Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry. 1999;56:254–260.Google Scholar
45.Altshuler, LL, Bartzokis, G, Grieder, T, et al.An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry. 2000;48:147–162.Google Scholar
46.Brambilla, P, Harenski, K, Nicoletti, M, et al.MRI investigation of temporal lobe structures in bipolar patients. J Psychiatr Res. 2003;37:287–295.Google Scholar
47.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.CrossRefGoogle ScholarPubMed
48.Filipek, PA, Semrud-Clikeman, M, Steingard, RJ, Renshaw, PF, Kennedy, DN, Biederman, J. Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology. 1997;48:589–601.CrossRefGoogle ScholarPubMed
49.Schumann, CM, Hamstra, J, Goodlin-Jones, BL, et al.The amygdale is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J Neurosci. 2004;24:6392–6401.CrossRefGoogle Scholar
50.Altshuler, LL, Bartzokis, G, Grieder, T, Curran, J. Mintz, J. Amygdala enlargement in bipolar disorder and hippocampal reduction in schizophrenia: an MRI study demonstrating neuroanatomic specificity. Arch Gen Psychiatry. 1998;55:663–664.Google Scholar
51.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.Google Scholar
52.Dupont, RM, Jernigan, TL, Heindel, W, et al.Magnetic resonance imaging and mood disorders. Localization of white matter and other subcortical abnormalities. Arch Gen Psychiatry. 1995;52:747–755.CrossRefGoogle ScholarPubMed
53.Seidman, LJ, Valera, EM, Makris, N. Structural brain imaging of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005;57:1263–1272.Google Scholar
54.Sassi, RB, Nicoletti, M, Brambilla, P, et al.Decreased pituitary volume in patients with bipolar disorder. Biol Psychiatry. 2001;50:271–280.Google Scholar
55.Stork, C, Renshaw, PF. Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry. 2005;10:900–919.Google Scholar
56.Urenjak, J, Williams, SR, Gadian, DG, Noble, M. Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types. J Neurosci. 1993;13:981–999.Google Scholar
57.DelBello, MP, Strakowski, SM. Neurochemical predictors of response to pharmacologic treatments for bipolar disorder. Curr Psychiatry Rep. 2004;6:466–472.CrossRefGoogle ScholarPubMed
58.Davanzo, P, Thomas, MA, Yue, K, et al.Decreased anterior cingulate myo-inositol/creatine spectroscopy resonance with lithium treatment in children with bipolar disorder. Neuropsychopharmacology. 2001;24:359–369.Google Scholar
59.Davanzo, P, Yue, K, Thomas, MA, et al.Proton magnetic resonance spectroscopy of bipolar disorder versus intermittent explosive disorder in children and adolescents. Am J Psychiatry. 2003;160:1442–1452.Google Scholar
60.Cecil, KM, DelBello, MP, Sellars, MC, Strakowski, SM. Proton magnetic resonance spectroscopy of the frontal lobe and cerebellar vermis in children with a mood disorder and a familial risk for bipolar disorders. J Child Adolesc Psychopharmacol. 2003;13:545–555.Google Scholar
61.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.CrossRefGoogle ScholarPubMed
62.Moore, CM, Demopulos, CM, Henry, ME, et al.Brain-to-serum lithium ratio and age: an in vivo magnetic resonance spectroscopy study. Am J Psychiatry. 2002;159:1240–1242.CrossRefGoogle ScholarPubMed
63.Castillo, M, Kwock, L. Courvoisie, H, Hooper, SR. Proton MR spectroscopy in children with bipolar affective disorder: preliminary observations. AJNR Am J Neuroradiol. 2000;21:832–838.Google Scholar
64.Moore, GJ, Bebchuk, JM, Parrish, JK, et al.Temporal dissociation between lithiuminduced changed in frontal lobe myo-inositol and clinical response in manic-depressive illness. Am J Psychiatry. 1999;156:1902–1908.Google Scholar
65.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.Google Scholar
66.DelBello, MP, Kowatch, RA. Neuroimaging in pediatric bipolar disorder. In: DelBello, MP, Geller, B, eds. Bipolar Disorder in Childhood and Early Adolescence. New York, NY: Guilford Press; 2003:158–174.Google Scholar
67.Blumberg, HP, Martin, A, Kaufman, J, et al.Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. Am J Psychiatry. 2003;160:1345–1347.Google Scholar
68.Chang, K, Adleman, NE, Dienes, K, Simeonova, DI, Memon, V, Reiss, A. Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation. Arch Gen Psychiatry. 2004;61:781–792.Google Scholar
69.Blumberg, HP, Leung, HC, Skudlarski, P, 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.Google Scholar
70.Blumberg, HP, Kaufman, J, Martin, A, Charney, DS, Krystal, JH, Peterson, BS. Significance of adolescent neurodevelopment for the neural circuitry of bipolar disorder. Ann N Y Acad Sci. 2004;1021:376–383.Google Scholar
71.Silverstone, PH, McGrath, BM, Kim, H. Bipolar disorder and myo-inositol: a review of the magnetic resonance spectroscopy findings. Bipolar Disord. 2005;7:1–10.Google Scholar
72.Moore, CM, Breeze, JL, Gruber, SA, et alCholine, myo-inositol and mood in bipolar disorder: a proton magnetic resonance spectroscopic imaging study of the anterior cingulate cortex. Bipolar Disord. 2000;2(3 pt 2):207–216.Google Scholar
73.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.CrossRefGoogle ScholarPubMed
74.Kato, T. Mitochondrial dysfunction in bipolar disorder: from 31P-magnetic resonance spectroscopic findings to their molecular mechanisms. Int Rev Neurobiol. 2005;63:21–40.Google Scholar
75.Wu, RH, O'Donnell, T, Ulrich, M, Asghar, SJ, Hanstock, CC, Silverstone, PH. Brain choline concentrations may not be altered in euthymic bipolar disorder patients chronically treated with either lithium or sodium valproate. Ann Gen Hosp Psychiatry. 2004;3:13.Google Scholar
76.Silverstone, PH, Bell, EC, Willson, MC, Dave, S, Wilman, AH. Lithium alters brain activation in bipolar disorder in a task- and state-dependent manner: an fMRI study. Ann Gen Psychiatry. 2005;4:14.Google Scholar
77.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.Google Scholar
78.Strakowski, SM, Adler, CM, Holland, SK, Mills, N, DelBello, MP. A preliminary FMRI study of sustained attention in euthymic, unmedicated bipolar disorder. Neuropsychopharmacology. 2004;29:1734–1740.CrossRefGoogle ScholarPubMed
79.Durston, S, Hulshoff, Pol HE, Casey, BJ, Giedd, JN, Buitelaar, JK, van Engeland, H. Anatomical MRI of the developing human brain: what have we learned? J Am Acad Child Adolesc Psychiatry. 2001;40:1012–1020.Google Scholar
80.Giedd, JN. Structural magnetic resonance imaging of the adolescent brain. Ann N Y Acad Sci. 2004;1021:77–85.Google Scholar
81.DelBello, MP, Findling, RL, Kushner, S, et al.A pilot controlled trial of topiramate for mania in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005;44:539–547.Google Scholar