Adolescent Psychiatry; Bipolar Disorder; Child Psychiatry; Depression; Magnetic Resonance Imaging; Psychiatry; Suicide; Mood Disorders; Diffusion Tensor Imaging; Neuropsychiatry
Psychiatry: Neuroscience Research Training Program (NRTP) | Psychotherapy Development Center | Stress & Addiction Clinical Research Program | Women's Behavioral Health Research, Division of | Yale Mood Disorders Research Program
Obesity Research Working Group
A focus of Dr. Blumberg's laboratory is the use of brain scanning techniques to elucidate the differences in brain circuitry that underlie mood disorders, and how these differences develop in children and adolescence and change over the lifespan into later life. The laboratory has identified differences in parts of the brain that are important in emotional regulation in bipolar disorder, including differences in the pattern of their development in the disorder. For example, the laboratory has identified amygdala differences that are present in adults with bipolar disorder and also in adolescents with bipolar disorder suggesting that these are features that appear early, at least by adolescence in the disorder. Differences in the ventral prefrontal cortex (a part of the brain that includes the orbitofrontal cortex, the part of the prefrontal cortex above the eyes) appear to progress over the course of adolescence in bipolar disorder. This suggests that early intervention might be able to prevent progression and help prognosis. Recently, they identified brain circuitry differences in adolescents and young adults who made suicide attempts. Preliminary evidence suggests treatment may reverse some of the brain differences and may have the potential to prevent mood disorder progression and suicide.
The lab is working intensively on genetic and environmental factors that may contribute to the brain differences and that may point to new prevention and treatment strategies. Brain scanning techniques used in this work include structural magnetic resonance imaging (MRI) to study the size and shape of brain structures (including cutting edge new methods with 7 Tesla MRI scanning), functional magnetic resonance imaging (fMRI) to study how the parts of the brain function individually and as part of brain circuits, and diffusion tensor imaging (DTI) to study the connections between brain structures.
Specialized Terms: Adolescence; Bipolar Disorder; Brain; Depression; Suicide; Development; Diffusion Tensor Imaging; Emotion; Endophenotype; Functional Magnetic Resonance Imaging; Magnetic Resonance Imaging; Mania; Manic Depressive Disorder; Neuropsychiatry; Neuroscience; Women
Extensive Research Description
Dr. Blumberg is the Director of The Yale Mood Disorders Research Program (MDRP). The MDRP is dedicated to understanding the science of mood disorders, including bipolar disorder (manic-depressive illness) and depression. The MDRP brings together a multi-disciplinary group of scientists from across the Yale campus in a highly collaborative research effort. The scientists use a wide variety of scientific methods to study how genetic and environmental factors affect the brain and influence the expression of mood disorders across the lifespan. Goals of the MDRP include the identification of biological markers for mood and related disorders and discovery of new treatment strategies. It is hoped that these research efforts will lead to new and improved methods for early detection and treatment, and someday prevention, of mood disorders and suicide.
- MRI Brain Scanning Studies of Adolescents and Adults with Bipolar Disorder and Depression
- MRI Brain Scanning Studies of Brain Development in Healthy Adolescents and Adults
- MRI Brain Scanning Studies of Youths At-Risk for Bipolar Disorder
- MRI and Gene Studies of Genes and the Brain
- MRI Study of Stress Effects on the Brain and Development of Mood and Substance Use Disorders
- MRI methods include: structural MRI, functional MRI, diffusion tensor imaging, and structural MRI and magnetic resonance imaging at 7 Tesla.
- Development of Novel Medication and Non-Medication Interventions to Reduce and Prevent Symptoms and Suicide
Multimodal imaging of fronto-limbic structure and function associated with suicide attempts in adolescents and young adults with bipolar disorder
Johnston, J.A.Y, F. Wang, J. Liu, B. Blond, A. Wallace, J. Liu, L. Spencer, E.T. C. Lippard, Purves, K.L., A. Landeros-Weisenberger, E. Hermes, B. Pittman, R. King, A. Martin, M. Oquendo, H.P. Blumberg. American Journal of Psychiatry, 2017, Jan 31:appiajp 201615050652. doi:10.1176/appi.ajp. 2016.15050652. [Epub ahead of print]
Effects of ANK3 variation on gray and white matter in bipolar disorder
Lippard, E.T.C., K.P. Jensen, F. Wang, J.A.Y. Johnston, L. Spencer, B. Pittman, J. Gelernter, H.P. Blumberg. Molecular Psychiatry, 2016 May 31. doi: 10.1038/mp.2016.76. [Epub ahead of print]
Anterior cortical development during adolescence in bipolar disorder
Najt, P., F. Wang, L. Spencer, J.A.Y. Johnston, E.T. Cox Lippard, B.P. Pittman, C. Lacadie, L.H. Staib, X. Papademetris, H.P. Blumberg. Biological Psychiatry. 2016, 79:303-310.
Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment
Edmiston, E.E., F. Wang, C.M. Mazure, J. Guiney, R. Sinha, L.C. Mayes, H.P. Blumberg. Archives of Pediatrics and Adolescent Medicine. 2011, 165:1069-1077.
Olfactocentric paralimbic cortex morphology in adolescents with bipolar disorder
Wang, F., J.H. Kalmar, F.Y. Womer, E.E. Edmiston, L.G. Chepenik, B. R. Chen, L. Spencer, H.P. Blumberg. Brain. 2011, 134:2005-2012.
Functional and structural connectivity between the perigenual anterior cingulate and amygdala in bipolar disorder
Wang, F., J.H. Kalmar, Y. He, M. Jackowski, L.G. Chepenik, E.E. Edmiston, K. Tie, G. Gong, M.P. Shah, M. Jones, J. Uderman, R.T. Constable, H.P. Blumberg. Biological Psychiatry. 2009, 66:516-521.
- Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study Blumberg, H.P., J.H. Krystal, R. Bansal, A. Martin, J. Dziura, K. Durkin, L. Martin, E. Gerard, D.S. Charney, B.S. Peterson. Biological Psychiatry. 2006, 59:611-618.
Amygdala and hippocampus volumes in adolescents and adults with bipolar disorder.
Blumberg HP, Kaufman J, Martin A, Whiteman R, Gore JC, Charney DS, Krystal JH, Peterson BS. Amygdala and hippocampus volumes in adolescents and adults with bipolar disorder. Archives of General Psychiatry 2003;60:1201-1208
A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices.
Blumberg HP, Leung HC, Skudlarski P, Lacadie C, Fredericks C, Harris B, Charney D, Gore JC, Krystal JH, Peterson BS. A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Archives of General Psychiatry 2003;60: 599-607.
- Rostral and orbital prefrontal dysfunction in the manic state of bipolar disorder Blumberg, H.P., E. Stern, S. Ricketts, D. Martinez, J. de Asis, T. White, J. Epstein, N. Isenberg, P.A. McBride, I. Kemperman, S. Emmerich, V. Dhawan, D. Eidelberg, J.H. Kocsis, D.A. Silbersweig. American Journal of Psychiatry. 1999, 156:1986-1988.
Full List of PubMed Publications
- Johnston JA, Wang F, Liu J, Blond BN, Wallace A, Liu J, Spencer L, Cox Lippard ET, Purves KL, Landeros-Weisenberger A, Hermes E, Pittman B, Zhang S, King R, Martin A, Oquendo MA, Blumberg HP: Multimodal Neuroimaging of Frontolimbic Structure and Function Associated With Suicide Attempts in Adolescents and Young Adults With Bipolar Disorder. Am J Psychiatry. 2017 Jan 31; 2017 Jan 31. PMID: 28135845
- Lippard ET, Mazure CM, Johnston JA, Spencer L, Weathers J, Pittman B, Wang F, Blumberg HP: Brain circuitry associated with the development of substance use in bipolar disorder and preliminary evidence for sexual dimorphism in adolescents. J Neurosci Res. 2017 Jan 2. PMID: 27870392
- Najt P, Wang F, Spencer L, Johnston JA, Cox Lippard ET, Pittman BP, Lacadie C, Staib LH, Papademetris X, Blumberg HP: Anterior Cortical Development During Adolescence in Bipolar Disorder. Biol Psychiatry. 2016 Feb 15; 2015 Apr 6. PMID: 26033826
- Liu J, Ren L, Womer FY, Wang J, Fan G, Jiang W, Blumberg HP, Tang Y, Xu K, Wang F: Alterations in amplitude of low frequency fluctuation in treatment-naïve major depressive disorder measured with resting-state fMRI. Hum Brain Mapp. 2014 Oct; 2014 Apr 17. PMID: 24740815
- Cox Lippard ET, Johnston JA, Blumberg HP: Neurobiological risk factors for suicide: insights from brain imaging. Am J Prev Med. 2014 Sep. PMID: 25145733
- de Zwarte SM, Johnston JA, Cox Lippard ET, Blumberg HP: Frontotemporal White Matter in Adolescents with, and at-Risk for, Bipolar Disorder. J Clin Med. 2014 Mar 10; 2014 Mar 10. PMID: 26237259
- Blond BN, Fredericks CA, Blumberg HP: Functional neuroanatomy of bipolar disorder: structure, function, and connectivity in an amygdala-anterior paralimbic neural system. Bipolar Disord. 2012 Jun. PMID: 22631619
- Liu J, Blond BN, van Dyck LI, Spencer L, Wang F, Blumberg HP: Trait and state corticostriatal dysfunction in bipolar disorder during emotional face processing. Bipolar Disord. 2012 Jun; 2012 Apr 24. PMID: 22524493
- Kerestes R, Bhagwagar Z, Nathan PJ, Meda SA, Ladouceur CD, Maloney K, Matuskey D, Ruf B, Saricicek A, Wang F, Pearlson GD, Phillips ML, Blumberg HP: Prefrontal cortical response to emotional faces in individuals with major depressive disorder in remission. Psychiatry Res. 2012 Apr 30; 2012 May 16. PMID: 22595508
- Blumberg HP: Euthymia, depression, and mania: what do we know about the switch? Biol Psychiatry. 2012 Apr 1. PMID: 22424111
- Chepenik LG, Wang F, Spencer L, Spann M, Kalmar JH, Womer F, Kale Edmiston E, Pittman B, Blumberg HP: Structure-function associations in hippocampus in bipolar disorder. Biol Psychol. 2012 Apr; 2012 Feb 10. PMID: 22342942
- Liu J, Chaplin TM, Wang F, Sinha R, Mayes LC, Blumberg HP: Stress reactivity and corticolimbic response to emotional faces in adolescents. J Am Acad Child Adolesc Psychiatry. 2012 Mar; 2012 Feb 1. PMID: 22365466
- Ho HP, Wang F, Papademetris X, Blumberg HP, Staib LH: Fasciculography: robust prior-free real-time normalized volumetric neural tract parcellation. IEEE Trans Med Imaging. 2012 Feb; 2011 Sep 12. PMID: 21914568
- Spann MN, Mayes LC, Kalmar JH, Guiney J, Womer FY, Pittman B, Mazure CM, Sinha R, Blumberg HP: Childhood abuse and neglect and cognitive flexibility in adolescents. Child Neuropsychol. 2012; 2011 Sep 26. PMID: 21942637
- Wang F, Bobrow L, Liu J, Spencer L, Blumberg HP: Corticolimbic functional connectivity in adolescents with bipolar disorder. PLoS One. 2012; 2012 Nov 21. PMID: 23185566
- Edmiston EE, Wang F, Kalmar JH, Womer FY, Chepenik LG, Pittman B, Gueorguieva R, Hur E, Spencer L, Staib LH, Constable RT, Fulbright RK, Papademetris X, Blumberg HP: Lateral ventricle volume and psychotic features in adolescents and adults with bipolar disorder. Psychiatry Res. 2011 Dec 30; 2011 Oct 30. PMID: 22041535
- Edmiston EE, Wang F, Mazure CM, Guiney J, Sinha R, Mayes LC, Blumberg HP: Corticostriatal-limbic gray matter morphology in adolescents with self-reported exposure to childhood maltreatment. Arch Pediatr Adolesc Med. 2011 Dec. PMID: 22147775
- Wang F, McIntosh AM, He Y, Gelernter J, Blumberg HP: The association of genetic variation in CACNA1C with structure and function of a frontotemporal system. Bipolar Disord. 2011 Nov-Dec. PMID: 22085483
- Wang F, Kalmar JH, Womer FY, Edmiston EE, Chepenik LG, Chen R, Spencer L, Blumberg HP: Olfactocentric paralimbic cortex morphology in adolescents with bipolar disorder. Brain. 2011 Jul; 2011 Jun 11. PMID: 21666263
- Saricicek A, Maloney K, Muralidharan A, Ruf B, Blumberg HP, Sanacora G, Lorberg B, Pittman B, Bhagwagar Z: Levetiracetam in the management of bipolar depression: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011 Jun; 2010 Oct 19. PMID: 21034692
- Gilbert KE, Kalmar JH, Womer FY, Markovich PJ, Pittman B, Nolen-Hoeksema S, Blumberg HP: Impulsivity in Adolescent Bipolar Disorder. Acta Neuropsychiatr. 2011 Apr. PMID: 21483649
- Blond BN, Blumberg HP: Functional neuroimaging research in bipolar disorder. Curr Top Behav Neurosci. 2011. PMID: 25236558
- Ho HP, Wang F, Papademetris X, Blumberg HP, Staib LH: Integrated parcellation and normalization using DTI fasciculography. Med Image Comput Comput Assist Interv. 2011. PMID: 21995010
- Beech RD, Lowthert L, Leffert JJ, Mason PN, Taylor MM, Umlauf S, Lin A, Lee JY, Maloney K, Muralidharan A, Lorberg B, Zhao H, Newton SS, Mane S, Epperson CN, Sinha R, Blumberg H, Bhagwagar Z: Increased peripheral blood expression of electron transport chain genes in bipolar depression. Bipolar Disord. 2010 Dec. PMID: 21176028
- Chepenik LG, Raffo M, Hampson M, Lacadie C, Wang F, Jones MM, Pittman B, Skudlarski P, Blumberg HP: Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder. Psychiatry Res. 2010 Jun 30; 2010 May 20. PMID: 20493671
- Amin Z, Kanarek K, Krupitsky E, Walderhaug E, Ilomäki R, Blumberg H, Price LH, Bhagwagar Z, Carpenter LL, Tyrka AR, Magnusson A, Landrø NI, Zvartau E, Gelernter J, Epperson CN, Räsänen P, Siironen J, Lappalainen J: A sequencing-based survey of functional APAF1 alleles in a large sample of individuals with affective illness and population controls. Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5. PMID: 19455599
- Womer FY, Wang F, Chepenik LG, Kalmar JH, Spencer L, Edmiston E, Pittman BP, Constable RT, Papademetris X, Blumberg HP: Sexually dimorphic features of vermis morphology in bipolar disorder. Bipolar Disord. 2009 Nov. PMID: 19839998
- Womer FY, Kalmar JH, Wang F, Blumberg HP: A ventral prefrontal-amygdala neural system in bipolar disorder: a view from neuroimaging research. Acta Neuropsychiatr. 2009 Oct. PMID: 26952770
- Womer FY, Kalmar JH, Wang F, Blumberg HP: A Ventral Prefrontal-Amygdala Neural System in Bipolar Disorder: A View from Neuroimaging Research. Acta Neuropsychiatr. 2009 Sep 23. PMID: 20676360
- Wang F, Kalmar JH, He Y, Jackowski M, Chepenik LG, Edmiston EE, Tie K, Gong G, Shah MP, Jones M, Uderman J, Constable RT, Blumberg HP: Functional and structural connectivity between the perigenual anterior cingulate and amygdala in bipolar disorder. Biol Psychiatry. 2009 Sep 1; 2009 May 9. PMID: 19427632
- Jiang Y, Edmiston E, Wang F, Blumberg HP, Staib LH, Papademetris X: Shape Comparison Using Perturbing Shape Registration. Proc IEEE Comput Soc Conf Comput Vis Pattern Recognit. 2009 Jun 20. PMID: 20386618
- Zuo L, Luo X, Listman JB, Kranzler HR, Wang S, Anton RF, Blumberg HP, Stein MB, Pearlson GD, Covault J, Charney DS, van Kammen DP, Price LH, Lappalainen J, Cramer J, Krystal JH, Gelernter J: Population admixture modulates risk for alcohol dependence. Hum Genet. 2009 Jun; 2009 Mar 22. PMID: 19306106
- Kalmar JH, Wang F, Chepenik LG, Womer FY, Jones MM, Pittman B, Shah MP, Martin A, Constable RT, Blumberg HP: Relation between amygdala structure and function in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2009 Jun. PMID: 19454919
- Kalmar JH, Wang F, Spencer L, Edmiston E, Lacadie CM, Martin A, Constable RT, Duncan JS, Staib LH, Papademetris X, Blumberg HP: Preliminary evidence for progressive prefrontal abnormalities in adolescents and young adults with bipolar disorder. J Int Neuropsychol Soc. 2009 May. PMID: 19402934
- Shah MP, Wang F, Kalmar JH, Chepenik LG, Tie K, Pittman B, Jones MM, Constable RT, Gelernter J, Blumberg HP: Role of variation in the serotonin transporter protein gene (SLC6A4) in trait disturbances in the ventral anterior cingulate in bipolar disorder. Neuropsychopharmacology. 2009 Apr; 2008 Nov 26. PMID: 19037205
- Chepenik LG, Fredericks C, Papademetris X, Spencer L, Lacadie C, Wang F, Pittman B, Duncan JS, Staib LH, Duman RS, Gelernter J, Blumberg HP: Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder. Neuropsychopharmacology. 2009 Mar; 2008 Aug 13. PMID: 18704093
- Ho HP, Papademetris X, Wang F, Blumberg HP, Staib LH: Volumetric shape model for oriented tubular structure from DTI data. Med Image Comput Comput Assist Interv. 2009. PMID: 20426091
- Blumberg HP, Wang F, Chepenik LG, Kalmar JH, Edmiston E, Duman RS, Gelernter J: Influence of vascular endothelial growth factor variation on human hippocampus morphology. Biol Psychiatry. 2008 Nov 15; 2008 Aug 15. PMID: 18707678
- Wang F, Kalmar JH, Edmiston E, Chepenik LG, Bhagwagar Z, Spencer L, Pittman B, Jackowski M, Papademetris X, Constable RT, Blumberg HP: Abnormal corpus callosum integrity in bipolar disorder: a diffusion tensor imaging study. Biol Psychiatry. 2008 Oct 15; 2008 Jul 11. PMID: 18620337
- Wang F, Jackowski M, Kalmar JH, Chepenik LG, Tie K, Qiu M, Gong G, Pittman BP, Jones MM, Shah MP, Spencer L, Papademetris X, Constable RT, Blumberg HP: Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging. Br J Psychiatry. 2008 Aug. PMID: 18669996
- Blumberg HP: Dimensions in the development of bipolar disorder. Biol Psychiatry. 2007 Jul 15. PMID: 17601484
- Shafritz KM, Collins SH, Blumberg HP: The interaction of emotional and cognitive neural systems in emotionally guided response inhibition. Neuroimage. 2006 May 15; 2006 Feb 9. PMID: 16480897
- Blumberg HP, Krystal JH, Bansal R, Martin A, Dziura J, Durkin K, Martin L, Gerard E, Charney DS, Peterson BS: Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study. Biol Psychiatry. 2006 Apr 1; 2006 Jan 18. PMID: 16414030
- Blumberg HP, Fredericks C, Wang F, Kalmar JH, Spencer L, Papademetris X, Pittman B, Martin A, Peterson BS, Fulbright RK, Krystal JH: Preliminary evidence for persistent abnormalities in amygdala volumes in adolescents and young adults with bipolar disorder. Bipolar Disord. 2005 Dec. PMID: 16403182
- Blumberg HP, Donegan NH, Sanislow CA, Collins S, Lacadie C, Skudlarski P, Gueorguieva R, Fulbright RK, McGlashan TH, Gore JC, Krystal JH: Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder. Psychopharmacology (Berl). 2005 Dec; 2005 Oct 26. PMID: 16249909
- Luo X, Kranzler HR, Zuo L, Wang S, Blumberg HP, Gelernter J: CHRM2 gene predisposes to alcohol dependence, drug dependence and affective disorders: results from an extended case-control structured association study. Hum Mol Genet. 2005 Aug 15; 2005 Jul 6. PMID: 16000316
- 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 Jun. PMID: 15251913
- Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, Charney DS, Krystal JH, Peterson BS: Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry. 2003 Dec. PMID: 14662552
- Donegan NH, Sanislow CA, Blumberg HP, Fulbright RK, Lacadie C, Skudlarski P, Gore JC, Olson IR, McGlashan TH, Wexler BE: Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry. 2003 Dec 1. PMID: 14643096
- Potenza MN, Leung HC, Blumberg HP, Peterson BS, Fulbright RK, Lacadie CM, Skudlarski P, Gore JC: An FMRI Stroop task study of ventromedial prefrontal cortical function in pathological gamblers. Am J Psychiatry. 2003 Nov. PMID: 14594746
- Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski P, Lacadie C, Fulbright RK, Gore JC, Charney DS, Krystal JH, Peterson BS: Frontostriatal abnormalities in adolescents with bipolar disorder: preliminary observations from functional MRI. Am J Psychiatry. 2003 Jul. PMID: 12832254
- Blumberg HP, Leung HC, Skudlarski P, Lacadie CM, Fredericks CA, Harris BC, Charney DS, Gore JC, Krystal JH, Peterson BS: A functional magnetic resonance imaging study of bipolar disorder: state- and trait-related dysfunction in ventral prefrontal cortices. Arch Gen Psychiatry. 2003 Jun. PMID: 12796223
- Blumberg HP, Charney DS, Krystal JH: Frontotemporal neural systems in bipolar disorder. Semin Clin Neuropsychiatry. 2002 Oct. PMID: 12382207