SST Interneuron Disease Association Evidence Quality

SST neurons are implicated in multiple neuropsychiatric conditions but the strength of evidence varies dramatically from strong genetic association (schizophrenia) to correlational postmortem findings (depression) to primarily computational evidence (epilepsy models).

{
  "papers": [
    {
      "doi": "10.1038/s41593-024-01834-w",
      "value": "SST interneurons identified as key cell type in cellular etiology of schizophrenia",
      "method": "GWAS + single-cell genomics",
      "metric": "Genetic association with schizophrenia",
      "cite_key": "Duncan2025",
      "condition": "case-control",
      "study_system": "human genetics",
      "value_source_sentence": "These cell types included somatostatin interneurons, excitatory neurons from the retrosplenial cortex and eccentric medium spiny-like neurons from the amygdala."
    },
    {
      "doi": "10.31083/ap43531",
      "value": "Meta-analysis shows altered GAD67 expression in GABAergic interneurons",
      "method": "meta-analysis of transcriptomics",
      "metric": "GABA gene expression in schizophrenia",
      "cite_key": "Singer2026",
      "condition": "schizophrenia vs control",
      "study_system": "human postmortem",
      "value_source_sentence": "Altered Expression of GABA-Related Genes in Schizophrenia: Insights from Meta-Analyses of Transcriptomic Studies."
    },
    {
      "doi": "10.1371/journal.pcbi.1010986",
      "value": "Reduced SST inhibition associated with treatment-resistant depression",
      "method": "in silico modeling",
      "metric": "SST inhibition reduction in depression",
      "cite_key": "Mazza2023",
      "condition": "depression model",
      "study_system": "computational model (human)",
      "value_source_sentence": "Reduced cortical inhibition by somatostatin-expressing (SST) interneurons has been strongly associated with treatment-resistant depression."
    },
    {
      "doi": "10.1073/pnas.1411131111",
      "value": "SST and PV neurons impaired by Nav1.1 mutation; excitatory neurons unaffected",
      "method": "patch-clamp electrophysiology",
      "metric": "SST excitability impairment in Dravet syndrome",
      "cite_key": "Tai2014",
      "condition": "Scn1a+/- mice",
      "study_system": "mouse model (Dravet)",
      "value_source_sentence": "Our results show that two major types of inhibitory neurons are impaired in generation of electrical signals by a DS mutation, whereas excitatory neurons are unaffected."
    }
  ],
  "comparison_id": "sst-disease-association-evidence",
  "comparison_name": "SST Interneuron Disease Association Evidence Quality",
  "comparison_type": "convergent evidence",
  "what_it_reveals": "SST neurons are implicated in multiple neuropsychiatric conditions but the strength of evidence varies dramatically from strong genetic association (schizophrenia) to correlational postmortem findings (depression) to primarily computational evidence (epilepsy models).",
  "homogeneity_check": {
    "caveats": "Evidence types are fundamentally different (genetic, transcriptomic, electrophysiological, computational); comparing across these requires acknowledging each addresses different levels of the causal chain",
    "n_definition": "Varies: GWAS sample size vs patch-clamp cells vs computational neurons",
    "scope_region": "Cortex broadly",
    "taxonomic_level": "SST class level",
    "scope_population": "SST interneurons (no subtype distinction)"
  },
  "suggested_plot_type": "heatmap"
}

[
  "paper:paper-238af7edcf3a",
  "paper:paper-5e55c354b46f",
  "paper:paper-855d0bdbad3b",
  "paper:paper-de69a1db5c29"
]

{
  "mode": "public_source_pointer_with_short_context",
  "notes": [
    "Local review repositories are read-only inputs.",
    "SciDEX stores paper metadata, structured evidence, file pointers, and short citation contexts; it does not copy full review prose."
  ],
  "source_commit_sha": "89b7e9787cd90e942b0adb531d549af3ddad30f1",
  "source_repository_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewSST"
}