|
|
| PMID |
|
|
| TITLE |
|
| Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations. |
|
| ABSTRACT |
|
| Importance |
|
| The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. |
| Objective |
|
| The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). |
| Design, Setting, and Patients |
|
| The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. |
| Main Outcomes and Measures |
|
| The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased. |
| Results |
|
| The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased. Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3). |
| Conclusions and Relevance |
|
| The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active episode. To determine whether subgroups of patients with MDD stratified according to the A/W criterion had a different degree of genetic overlap with obesity-related traits (body mass index [BMI] and levels of C-reactive protein [CRP] and leptin). This multicenter study assembled genome-wide genotypic and phenotypic measures from 14 data sets of the Psychiatric Genomics Consortium. Data sets were drawn from case-control, cohort, and population-based studies, including 26 628 participants with established psychiatric diagnoses and genome-wide genotype data. Data on BMI were available for 15 237 participants. Data were retrieved and analyzed from September 28, 2015, through May 20, 2017. Lifetime DSM-IV MDD was diagnosed using structured diagnostic instruments. Patients with MDD were stratified into subgroups according to change in the DSM-IV A/W symptoms as decreased or increased. Data included 11 837 participants with MDD and 14 791 control individuals, for a total of 26 628 participants (59.1% female and 40.9% male). Among participants with MDD, 5347 (45.2%) were classified in the decreased A/W and 1871 (15.8%) in the increased A/W subgroups. Common genetic variants explained approximately 10% of the heritability in the 2 subgroups. The increased A/W subgroup showed a strong and positive genetic correlation (SE) with BMI (0.53 [0.15]; P = 6.3 × 10-4), whereas the decreased A/W subgroup showed an inverse correlation (-0.28 [0.14]; P = .06). Furthermore, the decreased A/W subgroup had a higher polygenic risk for increased BMI (odds ratio [OR], 1.18; 95% CI, 1.12-1.25; P = 1.6 × 10-10) and levels of CRP (OR, 1.08; 95% CI, 1.02-1.13; P = 7.3 × 10-3) and leptin (OR, 1.09; 95% CI, 1.06-1.12; P = 1.7 × 10-3). The phenotypic associations between atypical depressive symptoms and obesity-related traits may arise from shared pathophysiologic mechanisms in patients with MDD. Development of treatments effectively targeting immunometabolic dysregulations may benefit patients with depression and obesity, both syndromes with important disability. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| pubmed |
2017/10/20 06:00 |
| medline |
2017/12/14 06:00 |
| entrez |
2017/10/20 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Milaneschi Y |
|
Milaneschi |
Yuri |
Y |
|
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands. |
| Lamers F |
|
Lamers |
Femke |
F |
|
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands. |
| Peyrot WJ |
|
Peyrot |
Wouter J |
WJ |
|
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands. |
| Baune BT |
|
Baune |
Bernhard T |
BT |
|
Discipline of Psychiatry, University of Adelaide, Adelaide, Australia. |
| Breen G |
|
Breen |
Gerome |
G |
|
National Institute for Health Research Biomedical Research Centre for Mental Health, King's College London, London, England. |
| Dehghan A |
|
Dehghan |
Abbas |
A |
|
Department of Epidemiology and Biostatistics, Imperial College London, London, England. |
| Forstner AJ |
|
Forstner |
Andreas J |
AJ |
|
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland. |
| Grabe HJ |
|
Grabe |
Hans J |
HJ |
|
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
| Homuth G |
|
Homuth |
Georg |
G |
|
Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany. |
| Kan C |
|
Kan |
Carol |
C |
|
South London and Maudsley National Health Service Foundation, London, England. |
| Lewis C |
|
Lewis |
Cathryn |
C |
|
Medical Research Council Social Genetic and Developmental Psychiatry Centre, King's College London, London, England. |
| Mullins N |
|
Mullins |
Niamh |
N |
|
Medical Research Council Social Genetic and Developmental Psychiatry Centre, King's College London, London, England. |
| Nauck M |
|
Nauck |
Matthias |
M |
|
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. |
| Pistis G |
|
Pistis |
Giorgio |
G |
|
Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland. |
| Preisig M |
|
Preisig |
Martin |
M |
|
Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland. |
| Rivera M |
|
Rivera |
Margarita |
M |
|
Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain. |
| Rietschel M |
|
Rietschel |
Marcella |
M |
|
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. |
| Streit F |
|
Streit |
Fabian |
F |
|
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. |
| Strohmaier J |
|
Strohmaier |
Jana |
J |
|
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. |
| Teumer A |
|
Teumer |
Alexander |
A |
|
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. |
| Van der Auwera S |
|
Van der Auwera |
Sandra |
S |
|
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. |
| Wray NR |
|
Wray |
Naomi R |
NR |
|
Queensland Brain Institute, University of Queensland, Brisbane, Australia. |
| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
|
Department of Biological Psychology, VU University Amsterdam, Amsterdam, the Netherlands. |
| Penninx BWJH |
|
Penninx |
Brenda W J H |
BWJH |
|
Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands. |
|
CHARGE Inflammation Working Group and the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium |
|
|
|
|
|
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Degan |
Abbas |
A |
|
| Wray |
Naomi R. |
NR |
|
| Ripke |
Stephan |
S |
|
| Mattheisen |
Manuel |
M |
|
| Trzaskowski |
Maciej |
|
|
| Adams |
Mark J . |
MJ. |
|
| Agerbo |
Esben |
E |
|
| Air |
Tracy M. |
TM |
|
| Andlauer |
Till F. M. |
TFM |
|
| Bacanu |
Silviu-Alin |
SA |
|
| Bækvad-Hansen |
Marie |
M |
|
| Beekman |
Aartjan T. F. |
ATF |
|
| Bigdeli |
Tim B. |
TB |
|
| Binder |
Elisabeth B. |
EB |
|
| Blackwood |
Douglas H. R. |
DHR |
|
| Bryois |
Julien |
J |
|
| Buttenschøn |
Henriette N. |
HN |
|
| Bybjerg-Grauholm |
Jonas |
J |
|
| Cai |
Na |
N |
|
| Castelao |
Enrique |
E |
|
| Christensen |
Jane Hvarregaard |
JH |
|
| Clarke |
Toni-Kim |
TK |
|
| Coleman |
Jonathan R. I. |
JRI |
|
| Colodro-Conde |
Lucía |
L |
|
| Couvy-Duchesne |
Baptiste |
B |
|
| Craddock |
Nick |
N |
|
| Crawford |
Gregory E. |
GE |
|
| Davies |
Gail |
G |
|
| Deary |
Ian J. |
IJ |
|
| Degenhardt |
Franziska |
F |
|
| Derks |
Eske M. |
EM |
|
| Direk |
Nese |
N |
|
| Eley |
Thalia C. |
TC |
|
| Escott-Price |
Valentina |
V |
|
| Farhadi Hassan Kiadeh |
Farnush |
F |
|
| Finucane |
Hilary K. |
HK |
|
| Forstner |
Andreas J. |
AJ |
|
| Frank |
Josef |
J |
|
| Gaspar |
Héléna A. |
HA |
|
| Gill |
Michael |
M |
|
| Goes |
Fernando S. |
FS |
|
| Gordon |
Scott D. |
SD |
|
| Hall |
Lynsey S. |
LS |
|
| Hansen |
Christine Søholm |
CS |
|
| Hansen |
Thomas F. |
TF |
|
| Herms |
Stefan |
S |
|
| Hickie |
Ian B. |
IB |
|
| Homuth |
Georg |
G |
|
| Horn |
Carsten |
C |
|
| Hottenga |
Jouke-Jan |
JJ |
|
| Ising |
Marcus |
M |
|
| Jansen |
Rick |
R |
|
| Jorgenson |
Eric |
E |
|
| Knowles |
James A. |
JA |
|
| Kohane |
Isaac S. |
IS |
|
| Kraft |
Julia |
J |
|
| Kretzschmar |
Warren W. |
WW |
|
| Krogh |
Jesper |
J |
|
| Kutalik |
Zoltán |
Z |
|
| Li |
Yihan |
Y |
|
| Lind |
Penelope A. |
PA |
|
| MacIntyre |
Donald J. |
DJ |
|
| MacKinnon |
Dean F. |
DF |
|
| McGrath |
Patrick |
P |
|
| McGuffin |
Peter |
P |
|
| Medland |
Sarah E. |
SE |
|
| Middeldorp |
Christel M. |
CM |
|
| Mihailov |
Evelin |
E |
|
| Milaneschi |
Yuri |
Y |
|
| Mondimore |
Francis M. |
FM |
|
| Montgomery |
Grant W. |
GW |
|
| Mostafavi |
Sara |
S |
|
| Mullins |
Niamh |
N |
|
| Nauck |
Matthias |
M |
|
| Ng |
Bernard |
B |
|
| Nivard |
Michel G. |
MG |
|
| Nyholt |
Dale R. |
DR |
|
| O’Reilly |
Paul F. |
PF |
|
| Oskarsson |
Hogni |
H |
|
| Owen |
Michael J. |
MJ |
|
| Painter |
Jodie N. |
JN |
|
| Pedersen |
Carsten Bøcker |
CB |
|
| Pedersen |
Marianne Giørtz |
MG |
|
| Peterson |
Roseann E. |
RE |
|
| Pettersson |
Erik |
E |
|
| Peyrot |
Wouter J. |
WJ |
|
| Pistis |
Giorgio |
G |
|
| Posthuma |
Danielle |
D |
|
| Quiroz |
Jorge A. |
JA |
|
| Qvist |
Per |
P |
|
| Riley |
Brien P. |
BP |
|
| Rivera |
Margarita |
M |
|
| Saeed Mirza |
Saira |
S |
|
| Schoevers |
Robert |
R |
|
| Schulte |
Eva C. |
EC |
|
| Shen |
Ling |
L |
|
| Shi |
Jianxin |
J |
|
| Shyn |
Stanley I. |
SI |
|
| Sigurdsson |
Engilbert |
E |
|
| Sinnamon |
Grant C. B. |
GCB |
|
| Smit |
Johannes H. |
JH |
|
| Smith |
Daniel J. |
DJ |
|
| Stefansson |
Hreinn |
H |
|
| Steinberg |
Stacy |
S |
|
| Streit |
Fabian |
F |
|
| Strohmaier |
Jana |
J |
|
| Tansey |
Katherine E. |
KE |
|
| Teismann |
Henning |
H |
|
| Teumer |
Alexander |
A |
|
| Thompson |
Wesley |
W |
|
| Thomson |
Pippa A. |
PA |
|
| Thorgeirsson |
Thorgeir E. |
TE |
|
| Traylor |
Matthew |
M |
|
| Treutlein |
Jens |
J |
|
| Trubetskoy |
Vassily |
V |
|
| Uitterlinden |
André G. |
AG |
|
| Umbricht |
Daniel |
D |
|
| Van der Auwera |
Sandra |
S |
|
| van Hemert |
Albert M. |
AM |
|
| Viktorin |
Alexander |
A |
|
| Visscher |
Peter M. |
PM |
|
| Wang |
Yunpeng |
Y |
|
| Webb |
Bradley T. |
BT |
|
| Weinsheimer |
Shantel Marie |
SM |
|
| Wellmann |
Jürgen |
J |
|
| Wu |
Yang |
Y |
|
| Xi |
Hualin S. |
HS |
|
| Witt |
Stephanie H. |
SH |
|
| Yang |
Jian |
J |
|
| Zhang |
Futao |
F |
|
| Arolt |
Volker |
V |
|
| Baune |
Bernhard T. |
BT |
|
| Berger |
Klaus |
K |
|
| Boomsma |
Dorret I. |
DI |
|
| Cichon |
Sven |
S |
|
| Dannlowski |
Udo |
U |
|
| de Geus |
E J C |
EJC |
|
| DePaulo |
J. Raymond |
JR |
|
| Domenici |
Enrico |
E |
|
| Domschke |
Katharina |
K |
|
| Esko |
Tõnu |
T |
|
| Grabe |
Hans J. |
HJ |
|
| Hamilton |
Steven P. |
SP |
|
| Hayward |
Caroline |
C |
|
| Heath |
Andrew C. |
AC |
|
| Kendler |
Kenneth S. |
KS |
|
| Kloiber |
Stefan |
S |
|
| Lewis |
Glyn |
G |
|
| Li |
Qingqin S. |
QS |
|
| Lucae |
Susanne |
S |
|
| Madden |
Pamela A. F. |
PAF |
|
| Magnusson |
Patrik K. |
PK |
|
| Martin |
Nicholas G. |
NG |
|
| McIntosh |
Andrew M. |
AM |
|
| Metspalu |
Andres |
A |
|
| Mors |
Ole |
O |
|
| Mortensen |
Preben Bo |
PB |
|
| Müller-Myhsok |
Bertram |
B |
|
| Nordentoft |
Merete |
M |
|
| Nöthen |
Markus M. |
MM |
|
| O’Donovan |
Michael C. |
MC |
|
| Paciga |
Sara A. |
SA |
|
| Pedersen |
Nancy L. |
NL |
|
| Penninx |
Brenda W. J. H. |
BWJH |
|
| Perlis |
Roy H. |
RH |
|
| Porteous |
David J. |
DJ |
|
| Potash |
James B. |
JB |
|
| Preisig |
Martin |
M |
|
| Rietschel |
Marcella |
M |
|
| Schaefer |
Catherine |
C |
|
| Schulze |
Thomas G. |
TG |
|
| Smoller |
Jordan W. |
JW |
|
| Stefansson |
Kari |
K |
|
| Tiemeier |
Henning |
H |
|
| Uher |
Rudolf |
R |
|
| Völzke |
Henry |
H |
|
| Weissman |
Myrna M. |
MM |
|
| Werge |
Thomas |
T |
|
| Lewis |
Cathryn M. |
CM |
|
| Levinson |
Douglas F. |
DF |
|
| Breen |
Gerome |
G |
|
| Børglum |
Anders D. |
AD |
|
| Sullivan |
Patrick F. |
PF |
|
|
| JOURNAL |
|
| VOLUME: 74 |
| ISSUE: 12 |
| TITLE: JAMA psychiatry |
| ISOABBREVIATION: JAMA Psychiatry |
| YEAR: 2017 |
| MONTH: 12 |
| DAY: 01 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2168-6238 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: JAMA Psychiatry |
| COUNTRY: United States |
| ISSNLINKING: 2168-622X |
| NLMUNIQUEID: 101589550 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Multicenter Study |
| Research Support, Non-U.S. Gov't |
| Research Support, N.I.H., Extramural |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| CommentIn |
JAMA Psychiatry. 2017 Dec 1;74(12):1189-1190 |
29049499 |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| MR/K026992/1 |
Medical Research Council |
United Kingdom |
| R01 MH080403 |
NIMH NIH HHS |
United States |
| U01 MH109532 |
NIMH NIH HHS |
United States |
| S10 OD018164 |
NIH HHS |
United States |
| U01 MH109528 |
NIMH NIH HHS |
United States |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adult |
|
| Body Mass Index |
|
| C-Reactive Protein |
analysis |
| Craving |
analysis |
| Depressive Disorder, Major |
metabolism |
| Diagnostic and Statistical Manual of Mental Disorders |
metabolism |
| Female |
metabolism |
| Genetic Predisposition to Disease |
metabolism |
| Genome-Wide Association Study |
metabolism |
| Humans |
metabolism |
| International Cooperation |
metabolism |
| Male |
metabolism |
| Obesity |
psychology |
| Psychiatric Status Rating Scales |
psychology |
| Weight Gain |
psychology |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 9007-41-4 |
C-Reactive Protein |
|
| OTHER ID's |
|
|
|
