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| PMID |
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| TITLE |
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| Atypical energy-related symptoms define biologically distinct subtypes of major depressive disorder. |
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| ABSTRACT |
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| Major depressive disorder (MDD) is a complex psychiatric disorder, characterized by a range of mood, cognitive, and neurovegetative symptoms. Current diagnostic criteria treat opposite symptom directions as equivalent; weight gain or loss, and increased or decreased sleep, each count toward a single diagnosis. We defined three subgroups of individuals meeting criteria for MDD: (hypersomnia with increased appetite/weight gain), (insomnia with appetite/weight loss), and an Uncategorized group, and conducted genome-wide association meta-analyses for each ( = 47,858, 156,624, and 215,828, respectively). We identified 27 genome-wide significant loci across subtypes, 4 for , 10 for and 13 for Uncategorized. showed higher SNP-based heritability (10.9%) and lower polygenicity (1.7% of SNPs) than (7.9%; 2.9%) or Uncategorized (8.6%; 5.3%), with larger effect sizes at its associated loci. The and subtypes were moderately genetically correlated ( = 0.64, se = 0.04). Metabolic traits emerged as a primary differentiator: correlated positively with BMI, metabolic syndrome, and related traits, whereas correlated weakly in the opposite direction. These findings show that the directionality of neurovegetative symptoms indexes genetic heterogeneity within MDD, with metabolic biology as a central axis of differentiation. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| medline |
2026/07/10 06:35 |
| pubmed |
2026/07/10 06:34 |
| entrez |
2026/07/10 05:13 |
| pmc-release |
2026/07/08 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Harder A |
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Harder |
Arvid |
A |
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| Wang R |
|
Wang |
Rujia |
R |
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| Bergstedt J |
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Bergstedt |
Jacob |
J |
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| Huider F |
|
Huider |
Floris |
F |
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| Kurvits S |
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Kurvits |
Siim |
S |
|
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| Thorp J |
|
Thorp |
Jackson |
J |
|
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| Gong T |
|
Gong |
Tong |
T |
|
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| Assary E |
|
Assary |
Elham |
E |
|
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| Thijssen AB |
|
Thijssen |
Anaïs B |
AB |
|
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| Merola GP |
|
Merola |
Giuseppe Pierpaolo |
GP |
|
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| Goula AA |
|
Goula |
Anastasia A |
AA |
|
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| Bentwood S |
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Bentwood |
Sam |
S |
|
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| Karlsson R |
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Karlsson |
Robert |
R |
|
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| Pasman JA |
|
Pasman |
Joelle A |
JA |
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| Fabbri C |
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Fabbri |
Chiara |
C |
|
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| Hickie IB |
|
Hickie |
Ian B |
IB |
|
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| Peyrot WJ |
|
Peyrot |
Wouter J |
WJ |
|
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| Levinson DF |
|
Levinson |
Douglas F |
DF |
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|
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium |
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| Potash JB |
|
Potash |
James B |
JB |
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| Shi J |
|
Shi |
Jianxin |
J |
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| Medland SE |
|
Medland |
Sarah E |
SE |
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| Mitchell BL |
|
Mitchell |
Brittany L |
BL |
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| Kwong ASF |
|
Kwong |
Alex S F |
ASF |
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| Eley TC |
|
Eley |
Thalia C |
TC |
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| Lewis CM |
|
Lewis |
Cathryn M |
CM |
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| Hamilton SP |
|
Hamilton |
Steven P |
SP |
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| Martin NG |
|
Martin |
Nicholas G |
NG |
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| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
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| Lehto K |
|
Lehto |
Kelli |
K |
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| Wray NR |
|
Wray |
Naomi R |
NR |
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| Breen G |
|
Breen |
Gerome |
G |
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| Penninx BWJH |
|
Penninx |
Brenda W J H |
BWJH |
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| Milaneschi Y |
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Milaneschi |
Yuri |
Y |
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| Marshall S |
|
Marshall |
Sally |
S |
|
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| Thomson PA |
|
Thomson |
Pippa A |
PA |
|
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| Lu Y |
|
Lu |
Yi |
Y |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: medRxiv : the preprint server for health sciences |
| ISOABBREVIATION: medRxiv |
| YEAR: 2026 |
| MONTH: Jul |
| DAY: 04 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: |
| ISSNTYPE: |
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| MEDLINE JOURNAL |
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| MEDLINETA: medRxiv |
| COUNTRY: United States |
| ISSNLINKING: |
| NLMUNIQUEID: 101767986 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Preprint |
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| COMMENTS AND CORRECTIONS |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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