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    Michael Mccarthy

    TitleAssociate Adjunct Professor
    SchoolUniversity of California, San Diego
    Address9500 Gilman Drive #9116-A
    CA La Jolla 92093
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      Dr. McCarthy earned a B.S. in Biochemistry and Psychology from the University of New Mexico, before completing his doctoral training in medicine and neuroscience at Ohio State University. Dr. McCarthy developed an interest in Bipolar Disorder during his psychiatry residency at UCSD (2005-2009), and subsequently completed a post-doctoral research fellowship in the molecular biology of mood disorders and chronobiology at UCSD. Dr McCarthy joined the UCSD faculty in 2011. He is presently sees patients in the VA San Diego mood-sleep clinic, is the principle investigator on funded basic and clinical research projects in Bipolar Disorder. He is the field editor for neurobiology for Acta Psychiatrica Scandinavica, and a member of the UCSD Clinical Translation Research Institute (CTRI), and Center for Circadian Biology (CCB).

      Research Interests

      Due to regular intervals of light and dark caused by the Earth’s rotation around the sun, circadian clock genes have been selected through evolution to assist living organisms (including humans) in dealing with changes in temperature, food availability and social interaction. These genes have been shown to govern not only sleep wake behaviors, but also the brain’s reward and motivation systems. For these reasons, clock genes have been implicated in mood disorders such as bipolar disorder and major depression, and also substances abuse disorders like alcoholism. Clinically, the potential for clock gene influence is reinforced by features of these illnesses in which the commonly encountered alterations in sleep wake cycles, appetite, and other rhythmic behaviors are responsive to light availability and/or season. Similarly, lithium, a medication for treating mood disorders, has effects on rhythmic daily behaviors and affects the expression of several clock genes.

      In the laboratory, we are using cell lines and DNA from psychiatric patients to examine circadian clock genes. We measure clock gene expression using bioluminescent reporter assays to determine if their rhythms are disturbed relative to cells from unaffected subjects, or if the expression rhythms respond differentially to conditions like lithium treatment or stress. We also examine genetic variants in candidate clock genes to determine if these are associated with clinical features of mood disorders such as lithium response. Where possible, we link associated genetic variants to functional differences in gene regulation.

      Clinical Focus

      I treat veterans suffering from disturbances in mood where bipolar disorder is considered as likely in the differential diagnosis. Therefore, many of my patients have bipolar disorder, but others may be diagnosed with major depression, personality disorders or psychotic disorders like schizophrenia. Many patients have multiple diagnoses, including post-traumatic stress disorder and substance use disorders. In some cases, I use pharmacogenetic tools or collect genetic samples in hopes of establishing biological predictors of medication response in the future.

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      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Tobe BTD, Crain AM, Winquist AM, Calabrese B, Makihara H, Zhao WN, Lalonde J, Nakamura H, Konopaske G, Sidor M, Pernia CD, Yamashita N, Wada M, Inoue Y, Nakamura F, Sheridan SD, Logan RW, Brandel M, Wu D, Hunsberger J, Dorsett L, Duerr C, Basa RCB, McCarthy MJ, Udeshi ND, Mertins P, Carr SA, Rouleau GA, Mastrangelo L, Li J, Gutierrez GJ, Brill LM, Venizelos N, Chen G, Nye JS, Manji H, Price JH, McClung CA, Akiskal HS, Alda M, Chuang DM, Coyle JT, Liu Y, Teng YD, Ohshima T, Mikoshiba K, Sidman RL, Halpain S, Haggarty SJ, Goshima Y, Snyder EY. Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis. Proc Natl Acad Sci U S A. 2017 May 30; 114(22):E4462-E4471. PMID: 28500272.
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      2. Cronin P, McCarthy MJ, Lim ASP, Salmon DP, Galasko D, Masliah E, De Jager PL, Bennett DA, Desplats P. Circadian alterations during early stages of Alzheimer's disease are associated with aberrant cycles of DNA methylation in BMAL1. Alzheimers Dement. 2017 Jun; 13(6):689-700. PMID: 27883893.
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      3. McCarthy MJ, Behimer G, Anderson JA, Riddle I. Caregiving for youth with co-occurring developmental disabilities and behavioral health issues when caregivers face additional health-related stressors: Analysis of risk and protective factors from a national sample. Res Dev Disabil. 2016 Dec; 59:399-409. PMID: 27721195.
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      4. Hou L, Bergen SE, Akula N, Song J, Hultman CM, Landén M, Adli M, Alda M, Ardau R, Arias B, Aubry JM, Backlund L, Badner JA, Barrett TB, Bauer M, Baune BT, Bellivier F, Benabarre A, Bengesser S, Berrettini WH, Bhattacharjee AK, Biernacka JM, Birner A, Bloss CS, Brichant-Petitjean C, Bui ET, Byerley W, Cervantes P, Chillotti C, Cichon S, Colom F, Coryell W, Craig DW, Cruceanu C, Czerski PM, Davis T, Dayer A, Degenhardt F, Del Zompo M, DePaulo JR, Edenberg HJ, Étain B, Falkai P, Foroud T, Forstner AJ, Frisén L, Frye MA, Fullerton JM, Gard S, Garnham JS, Gershon ES, Goes FS, Greenwood TA, Grigoroiu-Serbanescu M, Hauser J, Heilbronner U, Heilmann-Heimbach S, Herms S, Hipolito M, Hitturlingappa S, Hoffmann P, Hofmann A, Jamain S, Jiménez E, Kahn JP, Kassem L, Kelsoe JR, Kittel-Schneider S, Kliwicki S, Koller DL, König B, Lackner N, Laje G, Lang M, Lavebratt C, Lawson WB, Leboyer M, Leckband SG, Liu C, Maaser A, Mahon PB, Maier W, Maj M, Manchia M, Martinsson L, McCarthy MJ, McElroy SL, McInnis MG, McKinney R, Mitchell PB, Mitjans M, Mondimore FM, Monteleone P, Mühleisen TW, Nievergelt CM, Nöthen MM, Novák T, Nurnberger JI, Nwulia EA, Ösby U, Pfennig A, Potash JB, Propping P, Reif A, Reininghaus E, Rice J, Rietschel M, Rouleau GA, Rybakowski JK, Schalling M, Scheftner WA, Schofield PR, Schork NJ, Schulze TG, Schumacher J, Schweizer BW, Severino G, Shekhtman T, Shilling PD, Simhandl C, Slaney CM, Smith EN, Squassina A, Stamm T, Stopkova P, Streit F, Strohmaier J, Szelinger S, Tighe SK, Tortorella A, Turecki G, Vieta E, Volkert J, Witt SH, Wright A, Zandi PP, Zhang P, Zollner S, McMahon FJ. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. Hum Mol Genet. 2016 Aug 01; 25(15):3383-3394. PMID: 27329760.
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      5. McCarthy MJ, Wei H, Landgraf D, Le Roux MJ, Welsh DK. Disinhibition of the extracellular-signal-regulated kinase restores the amplification of circadian rhythms by lithium in cells from bipolar disorder patients. Eur Neuropsychopharmacol. 2016 Aug; 26(8):1310-9. PMID: 27216486.
        View in: PubMed
      6. Oedegaard KJ, Alda M, Anand A, Andreassen OA, Balaraman Y, Berrettini WH, Bhattacharjee A, Brennand KJ, Burdick KE, Calabrese JR, Calkin CV, Claasen A, Coryell WH, Craig D, DeModena A, Frye M, Gage FH, Gao K, Garnham J, Gershon E, Jakobsen P, Leckband SG, McCarthy MJ, McInnis MG, Maihofer AX, Mertens J, Morken G, Nievergelt CM, Nurnberger J, Pham S, Schoeyen H, Shekhtman T, Shilling PD, Szelinger S, Tarwater B, Yao J, Zandi PP, Kelsoe JR. The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample. BMC Psychiatry. 2016 May 05; 16:129. PMID: 27150464; PMCID: PMC4857276.
      7. McCarthy M. Suicide rates rise sharply in the US, figures show. BMJ. 2016 04 25; 353:i2355. PMID: 27112501.
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      8. Landgraf D, Joiner WJ, McCarthy MJ, Kiessling S, Barandas R, Young JW, Cermakian N, Welsh DK. The mood stabilizer valproic acid opposes the effects of dopamine on circadian rhythms. Neuropharmacology. 2016 Aug; 107:262-270. PMID: 27033596.
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      9. Hou L, Heilbronner U, Degenhardt F, Adli M, Akiyama K, Akula N, Ardau R, Arias B, Backlund L, Banzato CEM, Benabarre A, Bengesser S, Bhattacharjee AK, Biernacka JM, Birner A, Brichant-Petitjean C, Bui ET, Cervantes P, Chen GB, Chen HC, Chillotti C, Cichon S, Clark SR, Colom F, Cousins DA, Cruceanu C, Czerski PM, Dantas CR, Dayer A, Étain B, Falkai P, Forstner AJ, Frisén L, Fullerton JM, Gard S, Garnham JS, Goes FS, Grof P, Gruber O, Hashimoto R, Hauser J, Herms S, Hoffmann P, Hofmann A, Jamain S, Jiménez E, Kahn JP, Kassem L, Kittel-Schneider S, Kliwicki S, König B, Kusumi I, Lackner N, Laje G, Landén M, Lavebratt C, Leboyer M, Leckband SG, Jaramillo CAL, MacQueen G, Manchia M, Martinsson L, Mattheisen M, McCarthy MJ, McElroy SL, Mitjans M, Mondimore FM, Monteleone P, Nievergelt CM, Nöthen MM, Ösby U, Ozaki N, Perlis RH, Pfennig A, Reich-Erkelenz D, Rouleau GA, Schofield PR, Schubert KO, Schweizer BW, Seemüller F, Severino G, Shekhtman T, Shilling PD, Shimoda K, Simhandl C, Slaney CM, Smoller JW, Squassina A, Stamm T, Stopkova P, Tighe SK, Tortorella A, Turecki G, Volkert J, Witt S, Wright A, Young LT, Zandi PP, Potash JB, DePaulo JR, Bauer M, Reininghaus EZ, Novák T, Aubry JM, Maj M, Baune BT, Mitchell PB, Vieta E, Frye MA, Rybakowski JK, Kuo PH, Kato T, Grigoroiu-Serbanescu M, Reif A, Del Zompo M, Bellivier F, Schalling M, Wray NR, Kelsoe JR, Alda M, Rietschel M, McMahon FJ, Schulze TG. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet. 2016 Mar 12; 387(10023):1085-1093. PMID: 26806518; PMCID: PMC4814312 [Available on 03/12/17].
      10. Barandas R, Landgraf D, McCarthy MJ, Welsh DK. Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders. Curr Psychiatry Rep. 2015 Dec; 17(12):98. PMID: 26483181.
        View in: PubMed
      11. Mertens J, Wang QW, Kim Y, Yu DX, Pham S, Yang B, Zheng Y, Diffenderfer KE, Zhang J, Soltani S, Eames T, Schafer ST, Boyer L, Marchetto MC, Nurnberger JI, Calabrese JR, Oedegaard KJ, McCarthy MJ, Zandi PP, Alda M, Nievergelt CM, Mi S, Brennand KJ, Kelsoe JR, Gage FH, Yao J. Erratum: Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature. 2016 Feb 11; 530(7589):242. PMID: 26605530.
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      12. Mertens J, Wang QW, Kim Y, Yu DX, Pham S, Yang B, Zheng Y, Diffenderfer KE, Zhang J, Soltani S, Eames T, Schafer ST, Boyer L, Marchetto MC, Nurnberger JI, Calabrese JR, Ødegaard KJ, McCarthy MJ, Zandi PP, Alda M, Alba M, Nievergelt CM, Mi S, Brennand KJ, Kelsoe JR, Gage FH, Yao J. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature. 2015 Nov 05; 527(7576):95-9. PMID: 26524527; PMCID: PMC4742055.
      13. McCarthy MJ, Le Roux MJ, Wei H, Beesley S, Kelsoe JR, Welsh DK. Calcium channel genes associated with bipolar disorder modulate lithium's amplification of circadian rhythms. Neuropharmacology. 2016 Feb; 101:439-48. PMID: 26476274.
        View in: PubMed
      14. McCarthy M. Only 30% of Americans with HIV have virus in check, finds report. BMJ. 2014 Nov 27; 349:g7329. PMID: 25429969.
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      15. Landgraf D, McCarthy MJ, Welsh DK. Circadian clock and stress interactions in the molecular biology of psychiatric disorders. Curr Psychiatry Rep. 2014 Oct; 16(10):483. PMID: 25135782.
        View in: PubMed
      16. McCarthy MJ, Liang S, Spadoni AD, Kelsoe JR, Simmons AN. Whole brain expression of bipolar disorder associated genes: structural and genetic analyses. PLoS One. 2014; 9(6):e100204. PMID: 24941232; PMCID: PMC4062532.
      17. Salloum NC, McCarthy MJ, Leckband SG, Kelsoe JR. Towards the clinical implementation of pharmacogenetics in bipolar disorder. BMC Med. 2014 May 30; 12:90. PMID: 24885933; PMCID: PMC4039055.
      18. Landgraf D, McCarthy MJ, Welsh DK. The role of the circadian clock in animal models of mood disorders. Behav Neurosci. 2014 Jun; 128(3):344-59. PMID: 24660657.
        View in: PubMed
      19. McCarthy MJ. Oxidative stress: a link between cardiovascular disease and psychiatric illness? Acta Psychiatr Scand. 2014 Sep; 130(3):161-2. PMID: 24660876.
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      20. Frank E, Sidor MM, Gamble KL, Cirelli C, Sharkey KM, Hoyle N, Tikotzky L, Talbot LS, McCarthy MJ, Hasler BP. Circadian clocks, brain function, and development. Ann N Y Acad Sci. 2013 Dec; 1306:43-67. PMID: 24329517.
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      21. McCarthy MJ, Wei H, Marnoy Z, Darvish RM, McPhie DL, Cohen BM, Welsh DK. Genetic and clinical factors predict lithium's effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Transl Psychiatry. 2013 Oct 22; 3:e318. PMID: 24150227; PMCID: PMC3818008.
      22. McCarthy MJ, Fernandes M, Kranzler HR, Covault JM, Welsh DK. Circadian clock period inversely correlates with illness severity in cells from patients with alcohol use disorders. Alcohol Clin Exp Res. 2013 Aug; 37(8):1304-10. PMID: 23550834; PMCID: PMC3706548.
      23. Fornaro M, McCarthy MJ, De Berardis D, De Pasquale C, Tabaton M, Martino M, Colicchio S, Cattaneo CI, D'Angelo E, Fornaro P. Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study. Neuropsychiatr Dis Treat. 2013; 9:243-51. PMID: 23430979; PMCID: PMC3575211.
      24. McCarthy MJ, Welsh DK. Cellular circadian clocks in mood disorders. J Biol Rhythms. 2012 Oct; 27(5):339-52. PMID: 23010657.
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      25. McCarthy MJ, Nievergelt CM, Kelsoe JR, Welsh DK. A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response. PLoS One. 2012; 7(2):e32091. PMID: 22384149; PMCID: PMC3285204.
      26. McCarthy MJ, Duchemin AM, Neff NH, Hadjiconstantinou M. CREB involvement in the regulation of striatal prodynorphin by nicotine. Psychopharmacology (Berl). 2012 May; 221(1):143-53. PMID: 22086359.
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      27. Kripke DF, Nievergelt CM, Tranah GJ, Murray SS, McCarthy MJ, Rex KM, Parimi N, Kelsoe JR. Polymorphisms in melatonin synthesis pathways: possible influences on depression. J Circadian Rhythms. 2011 Aug 09; 9:8. PMID: 21827647; PMCID: PMC3177871.
      28. McCarthy MJ. The eyes are the window to the brain: reviewing oculomotor abnormalities in obsessive-compulsive disorder. Acta Psychiatr Scand. 2011 Aug; 124(2):85-6. PMID: 21740402.
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      29. McCarthy MJ, Zhang H, Neff NH, Hadjiconstantinou M. Desensitization of d-opioid receptors in nucleus accumbens during nicotine withdrawal. Psychopharmacology (Berl). 2011 Feb; 213(4):735-44. PMID: 20941594.
        View in: PubMed
      30. McCarthy MJ, Leckband SG, Kelsoe JR. Pharmacogenetics of lithium response in bipolar disorder. Pharmacogenomics. 2010 Oct; 11(10):1439-65. PMID: 21047205.
        View in: PubMed
      31. McCarthy MJ, Zhang H, Neff NH, Hadjiconstantinou M. Nicotine withdrawal and kappa-opioid receptors. Psychopharmacology (Berl). 2010 Jun; 210(2):221-9. PMID: 19806344.
        View in: PubMed
      32. McCarthy MJ, Barrett TB, Nissen S, Kelsoe JR, Turner EE. Allele specific analysis of the ADRBK2 gene in lymphoblastoid cells from bipolar disorder patients. J Psychiatr Res. 2010 Mar; 44(4):201-8. PMID: 19766236; PMCID: PMC2830298.
      33. McCarthy MJ. Internet monitoring of suicide risk in the population. J Affect Disord. 2010 May; 122(3):277-9. PMID: 19748681; PMCID: PMC2847052.
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