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Towards further understanding of the co-morbidity between attention deficit hyperactivity disorder and bipolar disorder: a MRI study of brain volumes

Published online by Cambridge University Press:  15 October 2007

J. Biederman ,
N. Makris ,
E. M. Valera ,
M. C. Monuteaux ,
J. M. Goldstein ,
S. Buka ,
D. L. Boriel ,
S. Bandyopadhyay ,
D. N. Kennedy  and
V. S. Caviness
...Show all authors
J. Biederman*
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
N. Makris
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
E. M. Valera
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
M. C. Monuteaux
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
J. M. Goldstein
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
S. Buka
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
D. L. Boriel
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
S. Bandyopadhyay
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
D. N. Kennedy
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
V. S. Caviness
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
G. Bush
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
M. Aleardi
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
P. Hammerness
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
S. V. Faraone
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
L. J. Seidman
Affiliation:
Clinical and Research Program in Pediatric Psychopharmacology, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA
*
*Address for correspondence: J. Biederman, M.D., Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital, Fruit Street, Warren 7, Boston, MA 02114, USA. (Email: [email protected])
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Abstract

Background

Although attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this co-morbidity is scarce. Our aim was to evaluate the morphometric magnetic resonance imaging (MRI) underpinnings of the co-morbidity of ADHD with BPD, testing the hypothesis that subjects with this co-morbidity would have neuroanatomical correlates of both disorders.

Method

Morphometric MRI findings were compared between 31 adults with ADHD and BPD and with those of 18 with BPD, 26 with ADHD, and 23 healthy controls. The volumes (cm3) of our regions of interest (ROIs) were estimated as a function of ADHD status, BPD status, age, sex, and omnibus brain volume using linear regression models.

Results

When BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, this pattern was found in co-morbid subjects with ADHD plus BPD. Likewise, when ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex and less cerebellar gray matter, so did co-morbid ADHD plus BPD subjects.

Conclusions

Our results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. In the co-morbid state of ADHD plus BPD, the profile of brain volumetric abnormalities consists of structures that are altered in both disorders individually. Attention to co-morbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD.

Keywords

ADHDbipolar disorderco-morbidityMRI
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 7 , July 2008 , pp. 1045 - 1056
Copyright
Copyright © 2007 Cambridge University Press

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References

Adler, CM, Delbello, MP, Jarvis, K, Levine, A, Adams, J, Strakowski, SM (2007). Voxel-based study of structural changes in first-episode patients with bipolar disorder. Biological Psychiatry 61, 776–781.CrossRefGoogle ScholarPubMed
Altshuler, L, Bookheimer, S, Proenza, MA, Townsend, J, Sabb, F, Firestine, A, Bartzokis, G, Mintz, J, Mazziotta, J, Cohen, MS (2005 a). Increased amygdala activation during mania: a functional magnetic resonance imaging study. American Journal of Psychiatry 162, 1211–1213.CrossRefGoogle Scholar
Altshuler, LL, Bookheimer, SY, Townsend, J, Proenza, MA, Eisenberger, N, Sabb, F, Mintz, J, Cohen, MS (2005 b). Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study. Biological Psychiatry 58, 763–769.CrossRefGoogle Scholar
Biederman, J, Faraone, SV, Wozniak, J, Monuteaux, MC (2000 a). Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis. Biological Psychiatry 48, 1037–1044.CrossRefGoogle ScholarPubMed
Biederman, J, Mick, E, Faraone, SV, Spencer, T, Wilens, TE, Wozniak, J (2000 b). Pediatric mania: a developmental subtype of bipolar disorder? Biological Psychiatry 48, 458–466.CrossRefGoogle Scholar
Biederman, J, Mick, E, Wozniak, J, Monuteaux, M, Galdo, M, Faraone, S (2003). Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program. Biological Psychiatry 53, 952–960.CrossRefGoogle ScholarPubMed
Blumberg, HP, Stern, E, Ricketts, S, Martinez, D, de Asis, J, White, T, Epstein, J, Isenberg, N, McBride, PA, Kemperman, I, Emmerich, S, Dhawan, V, Eidelberg, D, Kocsis, JH, Silbersweig, DA (1999). Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder. American Journal of Psychiatry 156, 1986–1988.CrossRefGoogle ScholarPubMed
Brambilla, P, Glahn, DC, Balestrieri, M, Soares, JC (2005). Magnetic resonance findings in bipolar disorder. Psychiatric Clinics of North America 28, 443–467.CrossRefGoogle ScholarPubMed
Buka, SL, Goldstein, JM, Seidman, LJ, Zornberg, GL, Donatelli, JA, Denny, LR, Tsuang, MT (1999). Impact of perinatal hypoxia and genetic vulnerability on schizophrenia: the New England longitudinal studies of schizophrenia. Psychiatric Annals 29, 151–156.CrossRefGoogle Scholar
Cabeza, R, Nyberg, L (2000). Imaging cognition II: an empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience 12, 1–47.CrossRefGoogle Scholar
Castellanos, FX, Lee, PP, Sharp, W, Jeffries, NO, Greenstein, DK, Clasen, LS, Blumenthal, JD, James, RS, Ebens, CL, Walter, JM, Zijdenbos, A, Evans, AC, Giedd, JN, Rapoport, JL (2002). Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder. Journal of the American Medical Association 288, 1740–1748.CrossRefGoogle ScholarPubMed
Caviness, VS Jr., Kennedy, DN, Richelme, C, Rademacher, J, Filipek, PA (1996 a). The human brain age 7–11 years: a volumetric analysis based on magnetic resonance images. Cerebral Cortex 6, 726–736.CrossRefGoogle Scholar
Caviness, VS Jr., Meyer, JW, Makris, N, Kennedy, DN (1996 b). MRI-based topographic parcellation of the human neocortex: an anatomically specified method with estimate of reliability. Journal of Cognitive Neuroscience 8, 566–587.CrossRefGoogle ScholarPubMed
Dupont, RM, Jernigan, TL, Heindel, W, Butters, N, Shafer, K, Wilson, T, Hesselink, J, Gillin, JC (1995). Magnetic resonance imaging and mood disorders. Localization of white matter and other subcortical abnormalities. Archives of General Psychiatry 52, 747–755.CrossRefGoogle ScholarPubMed
Elliott, R, Ogilvie, A, Rubinsztein, JS, Calderon, G, Dolan, RJ, Sahakian, BJ (2004). Abnormal ventral frontal response during performance of an affective go/no go task in patients with mania. Biological Psychiatry 55, 1163–1170.CrossRefGoogle ScholarPubMed
Faraone, S, Glatt, S, Tsuang, M (2003). The genetics of pediatric onset bipolar disorder. Biological Psychiatry 53, 970–977.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Feighner, JA, Monuteaux, MC (2000). Assessing symptoms of attention deficit hyperactivity disorder in children and adults: which is more valid? Journal of Consulting and Clinical Psychology 68, 830–842.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Mennin, D, Russell, RL (1998). Bipolar and antisocial disorders among relatives of ADHD children: parsing familial subtypes of illness. American Journal of Medical Genetics 81, 108–116.3.0.CO;2-N>CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Mennin, D, Wozniak, J, Spencer, T (1997). Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype? Journal of the American Academy of Child and Adolescent Psychiatry 36, 1378–1390.CrossRefGoogle ScholarPubMed
Faraone, SV, Biederman, J, Monuteaux, MC (2001). Attention deficit hyperactivity disorder with bipolar disorder in girls: further evidence for a familial subtype? Journal of Affective Disorders 64, 19–26.CrossRefGoogle ScholarPubMed
Filipek, PA, Richelue, C, Kennedy, DN, Caviness, VS (1994). The young adult human brain: an MRI-based morphometric study. Cerebral Cortex 267, 344–360.CrossRefGoogle Scholar
Filipek, PA, Semrud-Clikeman, M, Steingrad, R, Kennedy, D, Biederman, J (1997). Volumetric MRI analysis: comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology 48, 589–601.CrossRefGoogle ScholarPubMed
First, M, Spitzer, R, Gibbon, M, Williams, J (1997). Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Press: Washington, DC.Google Scholar
Frazier, JA, Breeze, JL, Makris, N, Giuliano, AS, Herbert, MR, Seidman, L, Biederman, J, Hodge, SM, Dieterich, ME, Gerstein, ED, Kennedy, DN, Rauch, SL, Cohen, BM, Caviness, VS (2005 a). Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder. Bipolar Disorders 7, 555–569.CrossRefGoogle ScholarPubMed
Frazier, JA, Chiu, S, Breeze, JL, Makris, N, Lange, N, Kennedy, DN, Herbert, MR, Bent, EK, Koneru, VK, Dieterich, ME, Hodge, SM, Rauch, SL, Grant, PE, Cohen, BM, Seidman, LJ, Caviness, VS, Biederman, J (2005 b). Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder. American Journal of Psychiatry 162, 1256–1265.CrossRefGoogle ScholarPubMed
Goldstein, J, Goodman, J, Seidman, L, Kennedy, D, Makris, N, Lee, H, Tourville, J, Caviness, V, Faraone, S, Tsuang, M (1999). Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. Archives of General Psychiatry 56, 537–547.CrossRefGoogle ScholarPubMed
Kennedy, DN, Filipek, PA, Caviness, JVS (1989). Autonomic segmentation and volumetric calculations in nuclear magnetic resonance imaging. IEEE Transactions on Medical Imaging 8, 1–7.CrossRefGoogle Scholar
Kessler, R, McGonagle, K, Zhao, S, Nelson, C, Hughes, M, Eshleman, S, Wittchen, H, Kendler, K (1994). Lifetime and 12 month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Archives of General Psychiatry 51, 8–19.CrossRefGoogle ScholarPubMed
Leckman, JF, Sholomskas, D, Thompson, D, Belanger, A, Weissman, MM (1982). Best estimate of lifetime psychiatric diagnosis: a methodological study. Archives of General Psychiatry 39, 879–883.CrossRefGoogle ScholarPubMed
Lopez-Larson, MP, DelBello, MP, Zimmerman, ME, Schwiers, ML, Strakowski, SM (2002). Regional prefrontal gray and white matter abnormalities in bipolar disorder. Biological Psychiatry 52, 93–100.CrossRefGoogle ScholarPubMed
Makris, N, Biederman, J, Valera, EM, Bush, G, Kaiser, J, Kennedy, DN, Caviness, VS, Faraone, SV, Seidman, LJ (2007). Cortical thinning of the attention and executive function networks in adults with attention-deficit/hyperactivity disorder. Cerebral Cortex 17, 1364–1375.CrossRefGoogle ScholarPubMed
Makris, N, Kaiser, J, Haselgrove, C, Seidman, LJ, Biederman, J, Boriel, D, Valera, EM, Papadimitriou, GM, Fischl, B, Caviness, V, Kennedy, DN (2006). Human cerebral cortex: a system of MRI-based volume-assisted topological parcellation. Neuroimage 33, 139–153.CrossRefGoogle Scholar
Makris, N, Meyer, J, Bates, J, Yeterian, E, Kennedy, D, Caviness, V (1999). MRI-based topographic parcellation of human cerebral white matter and nuclei. II. Rationale and applications with systematics of cerebral connectivity. Neuroimage 9, 18–45.CrossRefGoogle Scholar
McDonald, C, Zanelli, J, Rabe-Hesketh, S, Ellison-Wright, I, Sham, P, Kalidindi, S, Murray, RM, Kennedy, N (2004). Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder. Biological Psychiatry 56, 411–417.CrossRefGoogle ScholarPubMed
Middleton, FA, Strick, PL (2001). Cerebellar projections to the prefrontal cortex of the primate. Journal of Neuroscience 21, 700–712.CrossRefGoogle Scholar
Milberger, S, Biederman, J, Faraone, SV, Murphy, J, Tsuang, MT (1995). Attention deficit hyperactivity disorder and comorbid disorders: issues of overlapping symptoms. American Journal of Psychiatry 152, 1793–1799.Google ScholarPubMed
Ono, M, Kubik, S, Abarnathey, CD (1990). Atlas of the Cerebral Sulci. Thieme Medical Publishers: New York, NY.Google Scholar
Orvaschel, H (1994). Schedule for Affective Disorder and Schizophrenia for School-Age Children Epidemiologic Version. Nova Southeastern University, Center for Psychological Studies: Ft Lauderdale.Google Scholar
Rademacher, J (1992). Human cerebral cortex: localization, parcellation and morphometry with magnetic resonance imaging. Journal of Cognitive Neuroscience 4, 352–374.CrossRefGoogle ScholarPubMed
Rosso, IM, Killgore, WD, Cintron, CM, Gruber, SA, Tohen, M, Yurgelun-Todd, DA (2007). Reduced amygdala volumes in first-episode bipolar disorder and correlation with cerebral white matter. Biological Psychiatry 61, 743–749.CrossRefGoogle ScholarPubMed
Sachs, GS, Baldassano, CF, Truman, CJ, Guille, C (2000). Comorbidity of attention deficit hyperactivity disorder with early- and late-onset bipolar disorder. American Journal of Psychiatry 157, 466–468.CrossRefGoogle ScholarPubMed
Sax, K, Strakowski, S, Zimmerman, M, DelBello, M, Keck, P, Hawkins, J (1999). Frontosubcortical neuroanatomy and the continuous performance test in mania. American Journal of Psychiatry 156, 139–141.CrossRefGoogle ScholarPubMed
Schmahmann, JD, Sherman, JC (1998). The cerebellar cognitive affective syndrome. Brain 121 (Pt 4), 561–579.CrossRefGoogle ScholarPubMed
Seidman, LJ (2006). Neuropsychological functioning in people with ADHD across the lifespan. Clinical Psychology Review 26, 466–485.CrossRefGoogle ScholarPubMed
Seidman, LJ, Faraone, SV, Goldstein, JM, Goodman, JM, Kremen, WS, Toomey, R, Tourville, J, Kennedy, D, Makris, N, Caviness, VS, Tsuang, MT (1999). Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis. Biological Psychiatry 46, 941–954.CrossRefGoogle ScholarPubMed
Seidman, LJ, Valera, EM, Makris, N (2005). Structural brain imaging of attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 1263–1272.CrossRefGoogle ScholarPubMed
Seidman, LJ, Valera, EM, Makris, N, Monuteaux, MC, Boriel, DL, Kelkar, K, Kennedy, DN, Caviness, VS, Bush, G, Aleardi, M, Faraone, SV, Biederman, J (2006). Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging. Biological Psychiatry 60, 1071–1080.CrossRefGoogle ScholarPubMed
Shaffer, D (1994). Attention deficit hyperactivity disorder in adults. American Journal of Psychiatry 151, 633–638.Google ScholarPubMed
Soares, J, Mann, J (1997). The anatomy of mood disorders: review of structural neuroimaging studies. Biological Psychiatry 41, 86–106.CrossRefGoogle ScholarPubMed
Sowell, ER, Thompson, PM, Welcome, SE, Henkenius, AL, Toga, AW, Peterson, BS (2003). Cortical abnormalities in children and adolescents with attention-deficit hyperactivity disorder. Lancet 362, 1699–1707.CrossRefGoogle ScholarPubMed
Strakowski, SM, Delbello, MP, Adler, CM (2005). The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Molecular Psychiatry 10, 105–116.CrossRefGoogle ScholarPubMed
Strakowski, SM, DelBello, MP, Sax, KW, Zimmerman, ME, Shear, PK, Hawkins, JM, Larson, ER (1999). Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Archives of General Psychiatry 56, 254–260.CrossRefGoogle ScholarPubMed
Valera, EM, Faraone, SV, Biederman, J, Poldrack, RA, Seidman, LJ (2005). Functional neuroanatomy of working memory in adults with attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 439–447.CrossRefGoogle ScholarPubMed
Valera, EM, Faraone, SV, Murray, KE, Seidman, LJ (2007). Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry 61, 1361–1369.CrossRefGoogle ScholarPubMed
Wechsler, D (1981). Manual for the Wechsler Adult Intelligence Scale – Revised. The Psychological Corporation: San Antonio.Google Scholar
Weinberg, CR (1993). Toward a clearer definition of confounding. American Journal of Epidemiology 137, 1–8.CrossRefGoogle Scholar