Biotypes of deeply phenotyped depressed patients reflect signatures of adverse childhood experience and depressive cognitive biases Article Swipe
Federica Colombo
,
Federico Calesella
,
B. Bravi
,
L. Fortaner-Uyà
,
Camilla Monopoli
,
T. Cazzella
,
Maria Cristina Acconcia
,
Raffaella Zanardi
,
Cristina Colombo
,
Matteo Carminati
,
Chiara Fabbri
,
Alessandro Serretti
,
Irene Bollettini
,
Francesco Benedetti
,
Sara Poletti
,
Benedetta Vai
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.03.25330801
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.03.25330801
Background Negative Cognitive Styles (NCS) are key features of depression contributing to severe clinical outcomes by sustaining negative affect. However, depression is clinically heterogeneous, reflecting complex neurobiological and environmental interactions. Characterizing heterogeneity using multimodal data could help identify mechanisms mapping onto different phenotypes and discover high-impact biomarkers. Methods Using a stability-based relative clustering validation pipeline, 344 depressed patients (135 major depressive disorder, 209 bipolar disorder) were stratified based on multimodal neuroimaging data, including grey matter volumes, cortical thickness, white matter diffusivity indices, resting-state functional connectivity (FC), and spontaneous neural activity. Clusters were derived from each modality separately and in combination, and profiled for Adverse Childhood Experiences (ACEs) and NCS. Results All neuroimaging modalities stratified depressed patients into two clusters, with the FC-based model achieving the highest accuracy (85%). Compared with healthy controls (HC, N=138), these clusters exhibited opposite patterns of global functional hyper-integration (Cluster 1) and hyper-segregation (Cluster 2). Unique multivariate neurobiological-ACEs relationships characterized the FC-based clusters. While ACEs negatively affected FC in Cluster 1 and HC, Cluster 2 showed opposite effects specific to ACE subtypes, with sexual abuse positively influencing FC. Mediation analysis showed that FC strength mediated the relationship between ACEs and NCS of overgeneralize only in Cluster 2. ACE-related functional alterations pinpoint brain regions involved in socioemotional and cognitive development, sensitive to maturational neural changes. Conclusions These findings provide evidence of clinically meaningful depression “biotypes” shaped by ACEs and associated with NCS, underlining the feasibility of computational psychiatry tools to uncover data-driven patterns for precision psychiatry.
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Concepts
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.07.03.25330801
- https://www.medrxiv.org/content/medrxiv/early/2025/07/03/2025.07.03.25330801.full.pdf
- OA Status
- green
- References
- 90
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4411987367
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4411987367Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2025.07.03.25330801Digital Object Identifier
- Title
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Biotypes of deeply phenotyped depressed patients reflect signatures of adverse childhood experience and depressive cognitive biasesWork 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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2025-07-03Full publication date if available
- Authors
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Federica Colombo, Federico Calesella, B. Bravi, L. Fortaner-Uyà, Camilla Monopoli, T. Cazzella, Maria Cristina Acconcia, Raffaella Zanardi, Cristina Colombo, Matteo Carminati, Chiara Fabbri, Alessandro Serretti, Irene Bollettini, Francesco Benedetti, Sara Poletti, Benedetta VaiList of authors in order
- Landing page
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https://doi.org/10.1101/2025.07.03.25330801Publisher landing page
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https://www.medrxiv.org/content/medrxiv/early/2025/07/03/2025.07.03.25330801.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.medrxiv.org/content/medrxiv/early/2025/07/03/2025.07.03.25330801.full.pdfDirect OA link when available
- Concepts
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Adverse Childhood Experiences, Cognition, Depressive symptoms, Depression (economics), Psychology, Psychiatry, Clinical psychology, Medicine, Developmental psychology, Mental health, Economics, Keynesian economicsTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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90Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works_count | 90 |
| abstract_inverted_index.1 | 165 |
| abstract_inverted_index.2 | 169 |
| abstract_inverted_index.a | 50 |
| abstract_inverted_index.1) | 145 |
| abstract_inverted_index.2. | 201 |
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| abstract_inverted_index.2). | 149 |
| abstract_inverted_index.209 | 63 |
| abstract_inverted_index.344 | 56 |
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| abstract_inverted_index.HC, | 167 |
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