Polygenic contributions to lithium augmentation outcomes in antidepressant non-responders with unipolar depression Article Swipe
Julia Kraft
,
Pichit Buspavanich
,
Alice Braun
,
Georgia Panagiotaropoulou
,
Peter Schlattmann
,
Hannah Buchbauer
,
Karl Heilbron
,
Urs Heilbronner
,
Thomas G. Schulze
,
Stephan Ripke
,
Roland Ricken
,
Mazda Adli
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.22.25320940
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.22.25320940
Objective Lithium augmentation (LA) is an effective treatment for patients with major depression after inadequate antidepressant response, but therapeutic outcomes vary considerably between individuals. Molecular studies could yield novel insights into treatment prediction to enable personalized therapy choices. Here, we investigated the effects of polygenic risk scores (PRS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) on clinical outcomes following LA. Methods Recent GWAS summary statistics were used to construct disorder-specific PRS in lithium-augmented MDD patients who participated in a prospective study after poor response to at least one antidepressant drug. Depressive symptoms were assessed for four weeks or longer using the Hamilton Depression Rating Scale (HAMD). Hazard ratios (HR) of favorable outcomes, response (≥ 50% reduction in HAMD composite scores) and remission (HAMD ≤ 7), were estimated by Cox proportional hazards regression models adjusted for ancestry, demographic, and clinical covariates. Results In 193 patients, BIP-PRS was positively associated with both response (HR = 1.29, 95% CI = 1.02-1.63, p = 0.03, Nagelkerke R 2 = 2.51%) and remission (HR = 1.52, 95% CI = 1.14-2.04, p = 0.004, Nagelkerke R 2 = 4.53%) after LA. Our data further suggest that individuals who carry a lower polygenic burden for MDD tend to respond better to LA (HR = 0.81, 95% CI = 0.66-1.00, p = 0.048, Nagelkerke R 2 = 1.99%). No associations were observed between SCZ-PRS and either clinical outcome (p > 0.05). Conclusions Our findings indicate that individuals at higher polygenic risk for BIP and lower polygenic risk for MDD are more likely to benefit from augmentation with lithium. If replicated, PRS may inform future efforts to establish clinical prediction models for LA outcomes in unipolar depression.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.01.22.25320940
- OA Status
- green
- Cited By
- 2
- References
- 38
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406748724
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4406748724Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.01.22.25320940Digital Object Identifier
- Title
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Polygenic contributions to lithium augmentation outcomes in antidepressant non-responders with unipolar depressionWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-01-23Full publication date if available
- Authors
-
Julia Kraft, Pichit Buspavanich, Alice Braun, Georgia Panagiotaropoulou, Peter Schlattmann, Hannah Buchbauer, Karl Heilbron, Urs Heilbronner, Thomas G. Schulze, Stephan Ripke, Roland Ricken, Mazda AdliList of authors in order
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https://doi.org/10.1101/2025.01.22.25320940Publisher landing page
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1101/2025.01.22.25320940Direct OA link when available
- Concepts
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Antidepressant, Depression (economics), Lithium (medication), Psychology, Antidepressant medication, Psychiatry, Bipolar disorder, Medicine, Clinical psychology, Internal medicine, Anxiety, Economics, MacroeconomicsTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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38Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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