A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment

Amira Pierucci-Lagha; Jonathan Covault; Herbert L. Bonkovsky; Richard Feinn; Christine Abreu; Richard K. Sterling; Robert J. Fontana; Henry R. Kranzler; Gyongyi Szabo; Maureen Cormier; Donna Giansiracusa; Michelle Kelley; Adrian M. DiBisceglie; Bruce Bacon; Brent Neuschwander-Tetri; Debra King; Jules L. Dienstag; Andrea E. Reid; Raymond T. Chung; Wallis A. Molchen; Gregory T. Everson; Jennifer De-Santo; Carol McKinley; Timothy R. Morgan; John C. Hoefs; Choon Park; William M. Lee; Janel Shelton; Nicole Crowder; Rivka Elbein; Karen L. Lindsay; Carol B. Jones; Susan L. Milstein; Anna S F Lok; Pamela A. Richtmyer; Mitchell L. Shiffman; Charlotte Hofmann; Paula Smith; Marc G. Ghany; T. Jake Liang; Yoon Park; Elenita Rivera; Vanessa Haynes-Williams; James E. Everhart; Leonard B. Seeff; Patricia R. Robuck; Jay H. Hoofnagle; Elizabeth C. Wright; Chihiro Morishima; David R. Gretch; Minjun Chung; Latha Padmanabhan; Teresa M. Curto; Linda J. Massey; Zachary D. Goodman; Gary L. Davis; Guadalupe Garcia-Tsao; Michael Kutner; Stanley M. Lemon; Robert P. Perrillo

doi:10.1176/appi.psy.51.2.137

A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment

Amira Pierucci-Lagha, Jonathan Covault, Herbert L. Bonkovsky, Richard Feinn, Christine Abreu, Richard K. Sterling, Robert J. Fontana, Henry R. Kranzler, Gyongyi Szabo, Maureen Cormier, Donna Giansiracusa, Michelle Kelley, Adrian M. DiBisceglie, Bruce Bacon, Brent Neuschwander-Tetri, Debra King, Jules L. Dienstag, Andrea E. Reid, Raymond T. Chung, Wallis A. MolchenGregory T. Everson, Jennifer De-Santo, Carol McKinley, Timothy R. Morgan, John C. Hoefs, Choon Park, William M. Lee, Janel Shelton, Nicole Crowder, Rivka Elbein, Karen L. Lindsay, Carol B. Jones, Susan L. Milstein, Anna S F Lok, Pamela A. Richtmyer, Mitchell L. Shiffman, Charlotte Hofmann, Paula Smith, Marc G. Ghany, T. Jake Liang, Yoon Park, Elenita Rivera, Vanessa Haynes-Williams, James E. Everhart, Leonard B. Seeff, Patricia R. Robuck, Jay H. Hoofnagle, Elizabeth C. Wright, Chihiro Morishima, David R. Gretch, Minjun Chung, Latha Padmanabhan, Teresa M. Curto, Linda J. Massey, Zachary D. Goodman, Gary L. Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M. Lemon, Robert P. Perrillo

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Interferon-alpha (IFN-α) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. Objective: Defining relevant risk factors for IFN-α-induced depression is essential in order to identify prophylactic treatment strategies. Method: The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-α-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-α and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment. Results: Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-α-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. Conclusion: 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-α therapy for CHC in a population-specific manner.

Original language	English (US)
Pages (from-to)	137-148
Number of pages	12
Journal	Psychosomatics
Volume	51
Issue number	2
DOIs	https://doi.org/10.1176/appi.psy.51.2.137
State	Published - 2010

ASJC Scopus subject areas

Arts and Humanities (miscellaneous)
Applied Psychology
Psychiatry and Mental health

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Pierucci-Lagha, A., Covault, J., Bonkovsky, H. L., Feinn, R., Abreu, C., Sterling, R. K., Fontana, R. J., Kranzler, H. R., Szabo, G., Cormier, M., Giansiracusa, D., Kelley, M., DiBisceglie, A. M., Bacon, B., Neuschwander-Tetri, B., King, D., Dienstag, J. L., Reid, A. E., Chung, R. T., ... Perrillo, R. P. (2010). A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment. Psychosomatics, 51(2), 137-148. https://doi.org/10.1176/appi.psy.51.2.137

Pierucci-Lagha, A, Covault, J, Bonkovsky, HL, Feinn, R, Abreu, C, Sterling, RK, Fontana, RJ, Kranzler, HR, Szabo, G, Cormier, M, Giansiracusa, D, Kelley, M, DiBisceglie, AM, Bacon, B, Neuschwander-Tetri, B, King, D, Dienstag, JL, Reid, AE, Chung, RT, Molchen, WA, Everson, GT, De-Santo, J, McKinley, C, Morgan, TR, Hoefs, JC, Park, C, Lee, WM, Shelton, J, Crowder, N, Elbein, R, Lindsay, KL, Jones, CB, Milstein, SL, Lok, ASF, Richtmyer, PA, Shiffman, ML, Hofmann, C, Smith, P, Ghany, MG, Liang, TJ, Park, Y, Rivera, E, Haynes-Williams, V, Everhart, JE, Seeff, LB, Robuck, PR, Hoofnagle, JH, Wright, EC, Morishima, C, Gretch, DR, Chung, M, Padmanabhan, L, Curto, TM, Massey, LJ, Goodman, ZD, Davis, GL, Garcia-Tsao, G, Kutner, M, Lemon, SM & Perrillo, RP 2010, 'A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment', Psychosomatics, vol. 51, no. 2, pp. 137-148. https://doi.org/10.1176/appi.psy.51.2.137

@article{2e88593f9855440cb6b97517cb4ea6ae,

title = "A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment",

abstract = "Background: Interferon-alpha (IFN-α) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. Objective: Defining relevant risk factors for IFN-α-induced depression is essential in order to identify prophylactic treatment strategies. Method: The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-α-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-α and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment. Results: Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-α-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. Conclusion: 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-α therapy for CHC in a population-specific manner.",

author = "Amira Pierucci-Lagha and Jonathan Covault and Bonkovsky, {Herbert L.} and Richard Feinn and Christine Abreu and Sterling, {Richard K.} and Fontana, {Robert J.} and Kranzler, {Henry R.} and Gyongyi Szabo and Maureen Cormier and Donna Giansiracusa and Michelle Kelley and DiBisceglie, {Adrian M.} and Bruce Bacon and Brent Neuschwander-Tetri and Debra King and Dienstag, {Jules L.} and Reid, {Andrea E.} and Chung, {Raymond T.} and Molchen, {Wallis A.} and Everson, {Gregory T.} and Jennifer De-Santo and Carol McKinley and Morgan, {Timothy R.} and Hoefs, {John C.} and Choon Park and Lee, {William M.} and Janel Shelton and Nicole Crowder and Rivka Elbein and Lindsay, {Karen L.} and Jones, {Carol B.} and Milstein, {Susan L.} and Lok, {Anna S F} and Richtmyer, {Pamela A.} and Shiffman, {Mitchell L.} and Charlotte Hofmann and Paula Smith and Ghany, {Marc G.} and Liang, {T. Jake} and Yoon Park and Elenita Rivera and Vanessa Haynes-Williams and Everhart, {James E.} and Seeff, {Leonard B.} and Robuck, {Patricia R.} and Hoofnagle, {Jay H.} and Wright, {Elizabeth C.} and Chihiro Morishima and Gretch, {David R.} and Minjun Chung and Latha Padmanabhan and Curto, {Teresa M.} and Massey, {Linda J.} and Goodman, {Zachary D.} and Davis, {Gary L.} and Guadalupe Garcia-Tsao and Michael Kutner and Lemon, {Stanley M.} and Perrillo, {Robert P.}",

note = "Funding Information: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, the National Center for Research Resources (grant numbers are listed below), the National Institute on Alcohol Abuse and Alcoholism , Grant K24. AA13736 , and by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. ",

year = "2010",

doi = "10.1176/appi.psy.51.2.137",

language = "English (US)",

volume = "51",

pages = "137--148",

journal = "Psychosomatics",

issn = "0033-3182",

publisher = "American Psychiatric Publishing Inc.",

number = "2",

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TY - JOUR

T1 - A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment

AU - Pierucci-Lagha, Amira

AU - Covault, Jonathan

AU - Bonkovsky, Herbert L.

AU - Feinn, Richard

AU - Abreu, Christine

AU - Sterling, Richard K.

AU - Fontana, Robert J.

AU - Kranzler, Henry R.

AU - Szabo, Gyongyi

AU - Cormier, Maureen

AU - Giansiracusa, Donna

AU - Kelley, Michelle

AU - DiBisceglie, Adrian M.

AU - Bacon, Bruce

AU - Neuschwander-Tetri, Brent

AU - King, Debra

AU - Dienstag, Jules L.

AU - Reid, Andrea E.

AU - Chung, Raymond T.

AU - Molchen, Wallis A.

AU - Everson, Gregory T.

AU - De-Santo, Jennifer

AU - McKinley, Carol

AU - Morgan, Timothy R.

AU - Hoefs, John C.

AU - Park, Choon

AU - Lee, William M.

AU - Shelton, Janel

AU - Crowder, Nicole

AU - Elbein, Rivka

AU - Lindsay, Karen L.

AU - Jones, Carol B.

AU - Milstein, Susan L.

AU - Lok, Anna S F

AU - Richtmyer, Pamela A.

AU - Shiffman, Mitchell L.

AU - Hofmann, Charlotte

AU - Smith, Paula

AU - Ghany, Marc G.

AU - Liang, T. Jake

AU - Park, Yoon

AU - Rivera, Elenita

AU - Haynes-Williams, Vanessa

AU - Everhart, James E.

AU - Seeff, Leonard B.

AU - Robuck, Patricia R.

AU - Hoofnagle, Jay H.

AU - Wright, Elizabeth C.

AU - Morishima, Chihiro

AU - Gretch, David R.

AU - Chung, Minjun

AU - Padmanabhan, Latha

AU - Curto, Teresa M.

AU - Massey, Linda J.

AU - Goodman, Zachary D.

AU - Davis, Gary L.

AU - Garcia-Tsao, Guadalupe

AU - Kutner, Michael

AU - Lemon, Stanley M.

AU - Perrillo, Robert P.

N1 - Funding Information: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, the National Center for Research Resources (grant numbers are listed below), the National Institute on Alcohol Abuse and Alcoholism , Grant K24. AA13736 , and by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.

PY - 2010

Y1 - 2010

N2 - Background: Interferon-alpha (IFN-α) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. Objective: Defining relevant risk factors for IFN-α-induced depression is essential in order to identify prophylactic treatment strategies. Method: The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-α-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-α and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment. Results: Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-α-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. Conclusion: 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-α therapy for CHC in a population-specific manner.

AB - Background: Interferon-alpha (IFN-α) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life. Objective: Defining relevant risk factors for IFN-α-induced depression is essential in order to identify prophylactic treatment strategies. Method: The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-α-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-α and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment. Results: Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-α-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations. Conclusion: 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-α therapy for CHC in a population-specific manner.

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DO - 10.1176/appi.psy.51.2.137

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JO - Psychosomatics

JF - Psychosomatics

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ER -

A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-α treatment

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