Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

Jennie G. Pouget; Vanessa F. Gonçalves; Erika L. Nurmi; Christopher P Laughlin; Karyn S. Mallya; James T. McCracken; Michael G. Aman; Christopher J. McDougle; Lawrence Scahill; Virginia L. Misener; Arun K. Tiwari; Clement C. Zai; Eva J. Brandl; Daniel Felsky; Amy Q. Leung; Jeffrey A. Lieberman; Herbert Y. Meltzer; Steven G. Potkin; Charlotte Niedling; Werner Steimer; Stefan Leucht; Jo Knight; Daniel J. Müller; James L. Kennedy

doi:10.2217/pgs.14.158

Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

Jennie G. Pouget
, Vanessa F. Gonçalves
, Erika L. Nurmi
, Christopher P Laughlin
, Karyn S. Mallya
, James T. McCracken
, Michael G. Aman
, Christopher J. McDougle
, Lawrence Scahill
, Virginia L. Misener
, Arun K. Tiwari
, Clement C. Zai
, Eva J. Brandl
, Daniel Felsky
, Amy Q. Leung
, Jeffrey A. Lieberman
, Herbert Y. Meltzer
, Steven G. Potkin
, Charlotte Niedling
, Werner Steimer

Stefan Leucht, Jo Knight, Daniel J. Müller, James L. Kennedy

Centre for Addiction and Mental Health
University of Toronto Faculty of Medicine
University of Toronto
University of California
Ohio State University
Massachusetts General Hospital
Emory University School of Medicine
Charité – Universitätsmedizin Berlin
Vagelos College of Physicians and Surgeons
New York State Psychiatric Institute
Northwestern University Feinberg School of Medicine
University of California, Irvine
Technical University of Munich

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

13 Scopus citations

Abstract

Aim: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. Patients & methods: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). Results: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (p_uncor = 0.04) and RUPP samples (p = 3.00 × 10^-3), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10^-3) and RUPP samples (p = 2.76 × 10^-4). Conclusion: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect. Original submitted 20 August 2014; Revision submitted 3 November 201.

Original language	English
Pages (from-to)	5-22
Number of pages	18
Journal	Pharmacogenomics
Volume	16
Issue number	1
DOIs	https://doi.org/10.2217/pgs.14.158
State	Published - 1 Jan 2015

Keywords

SLC25A4
TSPO
adenine nucleotide translocator
antipsychotic
genetics
mitochondria
peripheral benzodiazepine receptor
pharmacogenomics
schizophrenia
translocator protein-18 kDa
weight gain

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10.2217/pgs.14.158

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Pouget, J. G., Gonçalves, V. F., Nurmi, E. L., P Laughlin, C., Mallya, K. S., McCracken, J. T., Aman, M. G., McDougle, C. J., Scahill, L., Misener, V. L., Tiwari, A. K., Zai, C. C., Brandl, E. J., Felsky, D., Leung, A. Q., Lieberman, J. A., Meltzer, H. Y., Potkin, S. G., Niedling, C., ... Kennedy, J. L. (2015). Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes. Pharmacogenomics, 16(1), 5-22. https://doi.org/10.2217/pgs.14.158

@article{550941bd98c843838464fa6f17a6db60,

title = "Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes",

abstract = "Aim: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. Patients \& methods: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). Results: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10-3), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10-3) and RUPP samples (p = 2.76 × 10-4). Conclusion: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect. Original submitted 20 August 2014; Revision submitted 3 November 201.",

keywords = "SLC25A4, TSPO, adenine nucleotide translocator, antipsychotic, genetics, mitochondria, peripheral benzodiazepine receptor, pharmacogenomics, schizophrenia, translocator protein-18 kDa, weight gain",

author = "Pouget, \{Jennie G.\} and Gon{\c c}alves, \{Vanessa F.\} and Nurmi, \{Erika L.\} and \{P Laughlin\}, Christopher and Mallya, \{Karyn S.\} and McCracken, \{James T.\} and Aman, \{Michael G.\} and McDougle, \{Christopher J.\} and Lawrence Scahill and Misener, \{Virginia L.\} and Tiwari, \{Arun K.\} and Zai, \{Clement C.\} and Brandl, \{Eva J.\} and Daniel Felsky and Leung, \{Amy Q.\} and Lieberman, \{Jeffrey A.\} and Meltzer, \{Herbert Y.\} and Potkin, \{Steven G.\} and Charlotte Niedling and Werner Steimer and Stefan Leucht and Jo Knight and M{\"u}ller, \{Daniel J.\} and Kennedy, \{James L.\}",

note = "Publisher Copyright: {\textcopyright} 2015 Future Medicine Ltd.",

year = "2015",

month = jan,

day = "1",

doi = "10.2217/pgs.14.158",

language = "English",

volume = "16",

pages = "5--22",

journal = "Pharmacogenomics",

issn = "1462-2416",

publisher = "Taylor and Francis Ltd.",

number = "1",

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Pouget, JG, Gonçalves, VF, Nurmi, EL, P Laughlin, C, Mallya, KS, McCracken, JT, Aman, MG, McDougle, CJ, Scahill, L, Misener, VL, Tiwari, AK, Zai, CC, Brandl, EJ, Felsky, D, Leung, AQ, Lieberman, JA, Meltzer, HY, Potkin, SG, Niedling, C, Steimer, W , Leucht, S, Knight, J, Müller, DJ & Kennedy, JL 2015, 'Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes', Pharmacogenomics, vol. 16, no. 1, pp. 5-22. https://doi.org/10.2217/pgs.14.158

TY - JOUR

T1 - Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

AU - Pouget, Jennie G.

AU - Gonçalves, Vanessa F.

AU - Nurmi, Erika L.

AU - P Laughlin, Christopher

AU - Mallya, Karyn S.

AU - McCracken, James T.

AU - Aman, Michael G.

AU - McDougle, Christopher J.

AU - Scahill, Lawrence

AU - Misener, Virginia L.

AU - Tiwari, Arun K.

AU - Zai, Clement C.

AU - Brandl, Eva J.

AU - Felsky, Daniel

AU - Leung, Amy Q.

AU - Lieberman, Jeffrey A.

AU - Meltzer, Herbert Y.

AU - Potkin, Steven G.

AU - Niedling, Charlotte

AU - Steimer, Werner

AU - Leucht, Stefan

AU - Knight, Jo

AU - Müller, Daniel J.

AU - Kennedy, James L.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Aim: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. Patients & methods: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). Results: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10-3), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10-3) and RUPP samples (p = 2.76 × 10-4). Conclusion: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect. Original submitted 20 August 2014; Revision submitted 3 November 201.

AB - Aim: TSPO is a neuroinflammatory biomarker and emerging therapeutic target in psychiatric disorders. We evaluated whether TSPO polymorphisms contribute to interindividual variability in schizophrenia, antipsychotic efficacy and antipsychotic-induced weight gain. Patients & methods: We analyzed TSPO polymorphisms in 670 schizophrenia cases and 775 healthy controls. Gene-gene interactions between TSPO and other mitochondrial membrane protein-encoding genes (VDAC1 and ANT1) were explored. Positive findings were evaluated in two independent samples (Munich, n = 300; RUPP, n = 119). Results: TSPO rs6971 was independently associated with antipsychotic-induced weight gain in the discovery (puncor = 0.04) and RUPP samples (p = 3.00 × 10-3), and interacted with ANT1 rs10024068 in the discovery (p = 1.15 × 10-3) and RUPP samples (p = 2.76 × 10-4). Conclusion: Our findings highlight TSPO as a candidate for future investigations of antipsychotic-induced weight gain, and support the involvement of mitochondrial membrane components in this serious treatment side effect. Original submitted 20 August 2014; Revision submitted 3 November 201.

KW - SLC25A4

KW - TSPO

KW - adenine nucleotide translocator

KW - antipsychotic

KW - genetics

KW - mitochondria

KW - peripheral benzodiazepine receptor

KW - pharmacogenomics

KW - schizophrenia

KW - translocator protein-18 kDa

KW - weight gain

UR - https://www.scopus.com/pages/publications/84920848024

U2 - 10.2217/pgs.14.158

DO - 10.2217/pgs.14.158

M3 - Article

C2 - 25560467

AN - SCOPUS:84920848024

SN - 1462-2416

VL - 16

SP - 5

EP - 22

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 1

ER -

Investigation of TSPO variants in schizophrenia and antipsychotic treatment outcomes

Abstract

Keywords

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