{
  "abstract": "Major depressive disorder (MDD) is associated with reduced hippocampal volume, altered connectivity and negative memory bias, suggesting disrupted hippocampal plasticity. Dysregulated adult hippocampal neurogenesis is a potential contributor, but its relevance in humans and role in MDD remain unclear. Here we investigated the molecular basis of hippocampal dysfunction in nonmedicated individuals with MDD by integrating analyses of neurogenic trajectories, cell-type- and subfield-specific gene expression, chromatin accessibility and protein expression. We identify a neurogenic lineage in the adult human hippocampal subgranular zone and provide evidence for a stalled neurogenic process in MDD, associated with transcriptional regulation, stress-related reprogramming and interferon signaling across developmental stages. Excitatory and inhibitory neurons show dysregulation of transcription factor networks affecting cell states. Cellular stress, excitatory-inhibitory imbalance, impaired synaptic plasticity, reduced metabolic capacity and immune activation, underlie impaired neurogenesis and reduced hippocampus circuit plasticity. Findings indicate genetic and epigenetic regulation of gene expression in MDD, and overlapping pathogenetic mechanisms with autoimmune, neurodevelopmental and neurodegenerative diseases. This work provides a new understanding of the pathogenesis of hippocampus-dependent cognitive symptoms in MDD and suggests potential therapeutic targets.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry, Columbia University, New York, NY, USA",
    "Research Foundation for Mental Hygiene - New York State Psychiatric Institute, New York, NY, USA",
    "Institute of Forensic Medicine Criminalistics and Medical Deontology, Ss. Cyril and Methodius University, Skopje, North Macedonia",
    "Macedonian Academy of Sciences & Arts, Skopje, North Macedonia",
    "Quantitative Proteomics and Metabolomics Center, Department of Biological Sciences, Columbia University, New York, NY, USA",
    "Department of Radiology, Columbia University, New York, NY, USA",
    "Department of Pathology and Cell Biology, Columbia University, New York, NY, USA",
    "Department of Neuroscience, Columbia University, New York, NY, USA",
    "Department of Pharmacology, Columbia University, New York, NY, USA",
    "Department of Biostatistics, Columbia University, New York, NY, USA",
    "Department of Psychiatry, Columbia University, New York, NY, USA. mb928@cumc.columbia.edu",
    "Research Foundation for Mental Hygiene - New York State Psychiatric Institute, New York, NY, USA. mb928@cumc.columbia.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Madeleine Peng"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jialin Jiang",
      "orcid": "0000-0002-3955-1016"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lucia Polizzi",
      "orcid": "0009-0001-7817-361X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tiancheng Shi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rakshitha Ramkumar",
      "orcid": "0009-0005-9304-0048"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Victor Anosike",
      "orcid": "0009-0002-2571-5275"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Giulia Guasoni"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexandra M. Wamalwa"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Madeline Mariani",
      "orcid": "0009-0006-8183-1173"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cheick A. Sissoko",
      "orcid": "0000-0001-8373-3450"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexandria N. Tartt",
      "orcid": "0000-0002-6089-7249"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Camille A. Fulmore",
      "orcid": "0000-0002-4682-6495"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Gorazd B. Rosoklija",
      "orcid": "0000-0003-2711-1694"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yung-yu Huang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Victoria Arango"
    },
    {
      "affs": [
        4
      ],
      "name": "Shujuan Tao McDonald"
    },
    {
      "affs": [
        2
      ],
      "name": "Natasha Bitoljanu"
    },
    {
      "affs": [
        0,
        5,
        1
      ],
      "name": "J. John Mann",
      "orcid": "0000-0002-0265-6586"
    },
    {
      "affs": [
        0
      ],
      "name": "Phi T. Nguyen",
      "orcid": "0000-0001-5598-9213"
    },
    {
      "affs": [
        6,
        0,
        3,
        1
      ],
      "name": "Andrew J. Dwork"
    },
    {
      "affs": [
        4
      ],
      "name": "Lewis M. Brown",
      "orcid": "0000-0002-5485-7419"
    },
    {
      "affs": [
        7,
        8,
        0,
        1
      ],
      "name": "René Hen",
      "orcid": "0000-0002-7763-4162"
    },
    {
      "affs": [
        9,
        0
      ],
      "name": "Hanga Galfalvy",
      "orcid": "0000-0001-7156-6106"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Maura B. Dupont"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/17grmy8tffy47.bib",
  "cited_by": 5,
  "doi": "10.1038/s41591-026-04571-8",
  "fulltext_url": null,
  "id": "17grmy8tffy47",
  "issns": [
    "1078-8956",
    "1546-170X",
    "1744-7933"
  ],
  "landing_url": "https://doi.org/10.1038/s41591-026-04571-8",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2806|Neurogenesis and neuroplasticity mechanisms"
    ]
  ],
  "openalex": "W7166532738",
  "pdf_url": null,
  "pmcid": "PMC13668758",
  "pmid": "42629468",
  "published": "2026-08-21",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/17grmy8tffy47.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T13:20:49Z",
      "native_id": "W7166532738",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41591-026-04571-8"
    }
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2806|Neurogenesis and neuroplasticity mechanisms",
      "subfield": "neuroscience"
    }
  ],
  "title": "Dysregulated adult hippocampal neurogenesis in major depressive disorder",
  "title_text": "Dysregulated adult hippocampal neurogenesis in major depressive disorder",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/17grmy8tffy47",
  "venue": "Nature Medicine",
  "versions": []
}