ArticleMolecular psychiatry2019
Altered serotonergic circuitry in SSRI-resistant major depressive disorder patient-derived neurons.
Article in Molecular psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.
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Who cites it
64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- The effect of coenzyme Q10 supplementation on depressive symptoms and anxiety: a systematic review and meta-analysis of randomized controlled trials.European journal of clinical pharmacology · 2025Pooled it
- Mental health dished up-the use of iPSC models in neuropsychiatric research.Journal of neural transmission (Vienna, Austria : 1996) · 2020Pooled it
- Identifying subgroups with differential response to CBASP versus Escitalopram during the first eight weeks of treatment in outpatients with persistent depressive disorder.European archives of psychiatry and clinical neuroscience · 2024Trial
- Model Systems infrastructure of the German Center for Mental Health (DZPG): toward an integrated, mechanism-based framework for mental health research.European archives of psychiatry and clinical neuroscience · 2026Review
- Functional precision psychiatry: iPSC-derived neurons as predictive assays for antidepressant response.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Time-dependent effects of rapid-acting antidepressants in iPSC-derived neurons from treatment-resistant depression and healthy volunteers.Molecular psychiatry · 2026Article
- Phenotypic screening of human iPSC-derived neurons identifies thienopyridones as neuritogenic small molecules.iScience · 2026Article
- Human-Derived Cellular Models in Psychiatry: A Focus on the Olfactory Neuroepithelium.Brain sciences · 2026Review
- Time-Dependent Effects of Rapid-Acting Antidepressants in iPSC-Derived Neurons from Treatment-Resistant Depression and Healthy Volunteers.Research square · 2026Article
- Genomic comparisons and the adaptive basis of brain size plasticity and chromosomal instability in the Eurasian common shrew.Molecular biology and evolution · 2026Article
- Environmental and genetic risk factors of depression converge on neuronal dysfunction driven by changes in cholesterol homeostasis.Developmental cell · 2026Article
- Genetic and epigenetic analysis of plasma glial fibrillary acidic protein (GFAP) levels in PTSD.Molecular psychiatry · 2026Article
- Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.Translational psychiatry · 2025Article
- iPSC-modelling reveals genetic associations and morphological alterations of oligodendrocytes in schizophrenia.Translational psychiatry · 2025Article
- Glucagon-like Peptide-1 Receptor Agonists: A New Frontier in Treating Alcohol Use Disorder.Brain sciences · 2025Review
- The regulatory variant rs1950834 confers the risk of depressive disorder by reducing LRFN5 expression.BMC medicine · 2025Article
- Lurasidone response in bipolar type I depression with childhood trauma exposure.The international journal of neuropsychopharmacology · 2025Observational
- Role of FPR2 antagonism in alleviating social isolation-induced depression and protecting blood-brain barrier integrity.Journal of neuroinflammation · 2025Article
- Model systems for emulating human tissue and physiology in psychiatric research.Frontiers in neuroscience · 2025Review
- iPSC-derived hindbrain organoids to evaluate escitalopram oxalate treatment responses targeting neuropsychiatric symptoms in Alzheimer's disease.Molecular psychiatry · 2024Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Disrupted serotonergic neurotransmission has long been implicated in major depressive disorder (MDD), for which selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment. However, a significant percentage of patients remain SSRI-resistant and it is unclear whether and how alterations in serotonergic neurons contribute to SSRI resistance in these patients. Induced pluripotent stem cells (iPSCs) facilitate the study of patient-specific neural subtypes that are typically inaccessible in living patients, enabling the discovery of disease-related phenotypes. In our study of a well-characterized cohort of over 800 MDD patients, we generated iPSCs and serotonergic neurons from three extreme SSRI-remitters (R) and SSRI-nonremitters (NR). We studied serotonin (5-HT) biochemistry and observed no significant differences in 5-HT release and reuptake or in genes related to 5-HT biochemistry. NR patient-derived serotonergic neurons exhibited altered neurite growth and morphology downstream of lowered expression of key Protocadherin alpha genes as compared to healthy controls and Rs. Furthermore, knockdown of Protocadherin alpha genes directly regulated iPSC-derived neurite length and morphology. Our results suggest that intrinsic differences in serotonergic neuron morphology and the resulting circuitry may contribute to SSRI resistance in MDD patients.
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Registered trials
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