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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

  • J. Biederman (a1), N. Makris (a1), E. M. Valera (a1), M. C. Monuteaux (a1), J. M. Goldstein (a1), S. Buka (a1), D. L. Boriel (a1), S. Bandyopadhyay (a1), D. N. Kennedy (a1), V. S. Caviness (a1), G. Bush (a1), M. Aleardi (a1), P. Hammerness (a1), S. V. Faraone (a1) and L. J. Seidman (a1)...

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.

Copyright

Corresponding author

*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: jbiederman@partners.org)

References

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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, 776781.
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, 12111213.
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, 763769.
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, 10371044.
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, 458466.
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, 952960.
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, 19861988.
Brambilla, P, Glahn, DC, Balestrieri, M, Soares, JC (2005). Magnetic resonance findings in bipolar disorder. Psychiatric Clinics of North America 28, 443467.
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, 151156.
Cabeza, R, Nyberg, L (2000). Imaging cognition II: an empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience 12, 147.
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, 17401748.
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, 726736.
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, 566587.
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, 747755.
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, 11631170.
Faraone, S, Glatt, S, Tsuang, M (2003). The genetics of pediatric onset bipolar disorder. Biological Psychiatry 53, 970977.
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, 830842.
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, 108116.
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, 13781390.
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, 1926.
Filipek, PA, Richelue, C, Kennedy, DN, Caviness, VS (1994). The young adult human brain: an MRI-based morphometric study. Cerebral Cortex 267, 344360.
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, 589601.
First, M, Spitzer, R, Gibbon, M, Williams, J (1997). Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Press: Washington, DC.
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, 555569.
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, 12561265.
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, 537547.
Kennedy, DN, Filipek, PA, Caviness, JVS (1989). Autonomic segmentation and volumetric calculations in nuclear magnetic resonance imaging. IEEE Transactions on Medical Imaging 8, 17.
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, 819.
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, 879883.
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, 93100.
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, 13641375.
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, 139153.
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, 1845.
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, 411417.
Middleton, FA, Strick, PL (2001). Cerebellar projections to the prefrontal cortex of the primate. Journal of Neuroscience 21, 700712.
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, 17931799.
Ono, M, Kubik, S, Abarnathey, CD (1990). Atlas of the Cerebral Sulci. Thieme Medical Publishers: New York, NY.
Orvaschel, H (1994). Schedule for Affective Disorder and Schizophrenia for School-Age Children Epidemiologic Version. Nova Southeastern University, Center for Psychological Studies: Ft Lauderdale.
Rademacher, J (1992). Human cerebral cortex: localization, parcellation and morphometry with magnetic resonance imaging. Journal of Cognitive Neuroscience 4, 352374.
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, 743749.
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, 466468.
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, 139141.
Schmahmann, JD, Sherman, JC (1998). The cerebellar cognitive affective syndrome. Brain 121 (Pt 4), 561579.
Seidman, LJ (2006). Neuropsychological functioning in people with ADHD across the lifespan. Clinical Psychology Review 26, 466485.
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, 941954.
Seidman, LJ, Valera, EM, Makris, N (2005). Structural brain imaging of attention-deficit/hyperactivity disorder. Biological Psychiatry 57, 12631272.
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, 10711080.
Shaffer, D (1994). Attention deficit hyperactivity disorder in adults. American Journal of Psychiatry 151, 633638.
Soares, J, Mann, J (1997). The anatomy of mood disorders: review of structural neuroimaging studies. Biological Psychiatry 41, 86106.
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, 16991707.
Strakowski, SM, Delbello, MP, Adler, CM (2005). The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings. Molecular Psychiatry 10, 105116.
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, 254260.
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, 439447.
Valera, EM, Faraone, SV, Murray, KE, Seidman, LJ (2007). Meta-analysis of structural imaging findings in attention-deficit/hyperactivity disorder. Biological Psychiatry 61, 13611369.
Wechsler, D (1981). Manual for the Wechsler Adult Intelligence Scale – Revised. The Psychological Corporation: San Antonio.
Weinberg, CR (1993). Toward a clearer definition of confounding. American Journal of Epidemiology 137, 18.

Keywords

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

  • J. Biederman (a1), N. Makris (a1), E. M. Valera (a1), M. C. Monuteaux (a1), J. M. Goldstein (a1), S. Buka (a1), D. L. Boriel (a1), S. Bandyopadhyay (a1), D. N. Kennedy (a1), V. S. Caviness (a1), G. Bush (a1), M. Aleardi (a1), P. Hammerness (a1), S. V. Faraone (a1) and L. J. Seidman (a1)...

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