Antidepressive Agents; Bipolar Disorder; Neurosciences; Psychiatry; Neurogenesis
Our laboratory is interested in the roles of transcription factors and adult neurogenesis in the neurobiology of psychiatric disorders. We are approaching this question in two related ways. First, in the clinical arena, we are conducting microarray studies to look at changes in expression of growth factor-related genes in peripheral blood of patients being treated with antidepressant medications. Current theories regarding the mechanism of action of both mood stabilizers and antidepressants suggest that the effects of these medications are medicated by the induction of specific genes in the brain. However, the relationship of these changes to disease-state and treatment-response remains unclear because the tissue of interest (the patient's brain) is not, under normal circumstances available for study.
An emerging alternative is to look for biomarkers in a surrogate tissue such as blood since the signaling pathways affected by these medications are present in a wide variety of peripheral tissues, including blood. The long-term goal of this project is to identify molecular biomarkers that are predictive of changes in mood-state and/or positive treatment-response to aid in the treatment of mood disorders including depression and bipolar disorder. A second area of interest involves animal studies aimed at understanding on the role of adult neurogenesis in psychiatric disorders. Patients with major depression, bipolar disorder and schizophrenia have all been found to have decreased hippocampal volumes, suggesting that decreased hippocampal cell number may be a common endophenotype in multiple mental illnesses.
Specialized Terms: Addictions Psychiatry; Bipolar Disorder; Molecular Neuroscience
- Cocaine Beech, R.D. and Sinha, R. (2011) “Cocaine” in Addiction Medicine: Science and Practice, Johnson, B.A. ed. (Springer, New York) pp. 397-416.
Increased peripheral blood expression of electron transport chain genes in bipolar depression
Beech, R.D. ,Lowthert, L., Leffert, J.J., Mason, P.N.,Taylor, M.M., Umlauf, S., Lin, A., Lee, J.Y., Maloney, K., Muralidharan, A., Lorberg, B., Zhao, H., Newton, S.S., Mane, S., Epperson, C.N., Sinha, R., Blumberg, H., and Bhagwagar, Z. (2010) "Increased peripheral blood expression of electron transport chain genes in bipolar depression." Bipolar Disorders 12: 813-24.
Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice
Kinsler R, Taylor MM, Flores NM, Leffert JJ, Beech RD. Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice. Synapse. 2010; 64(2):169-171.
Full List of PubMed Publications
- Beech RD, Leffert JJ, Lin A, Hong KA, Hansen J, Umlauf S, Mane S, Zhao H, Sinha R: Stress-related alcohol consumption in heavy drinkers correlates with expression of miR-10a, miR-21, and components of the TAR-RNA-binding protein-associated complex. Alcohol Clin Exp Res. 2014 Nov. PMID: 25421511
- Beech RD, Qu J, Leffert JJ, Lin A, Hong KA, Hansen J, Umlauf S, Mane S, Zhao H, Sinha R: Altered expression of cytokine signaling pathway genes in peripheral blood cells of alcohol dependent subjects: preliminary findings. Alcohol Clin Exp Res. 2012 Sep; 2012 Apr 4. PMID: 22471388
- 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
- Kinsler R, Taylor MM, Flores NM, Leffert JJ, Beech RD: Altered response to antidepressant treatment in FoxG1 heterozygous knockout mice. Synapse. 2010 Feb. PMID: 19852072
- Cheng E, Trombetta SE, Kovacs D, Beech RD, Ariyan S, Reyes-Mugica M, McNiff JM, Narayan D, Kluger HM, Picardo M, Halaban R: Rab33A: characterization, expression, and suppression by epigenetic modification. J Invest Dermatol. 2006 Oct; 2006 Jun 29. PMID: 16810302
- Harrist A, Beech RD, King SL, Zanardi A, Cleary MA, Caldarone BJ, Eisch A, Zoli M, Picciotto MR: Alteration of hippocampal cell proliferation in mice lacking the beta 2 subunit of the neuronal nicotinic acetylcholine receptor. Synapse. 2004 Dec 15. PMID: 15472930
- Caldarone BJ, Harrist A, Cleary MA, Beech RD, King SL, Picciotto MR: High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation. Biol Psychiatry. 2004 Nov 1. PMID: 15522249
- Beech RD, Cleary MA, Treloar HB, Eisch AJ, Harrist AV, Zhong W, Greer CA, Duman RS, Picciotto MR: Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons. J Comp Neurol. 2004 Jul 12. PMID: 15176089