ArticleNeurobiology of stress2020
Severe childhood and adulthood stress associates with neocortical layer-specific reductions of mature spines in psychiatric disorders.
Article in Neurobiology of stress, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Postmortem evidence of decreased brain pH in major depressive disorder: a systematic review and meta-analysis.Translational psychiatry · 2024Pooled it
- Ayahuasca Impairs Fear Memory Reconsolidation and Promotes Rapid Structural Plasticity in the Hippocampus and Prelimbic Cortex.Molecular neurobiology · 2026Article
- NMDA receptor-dependent structural plasticity links early life stress to persistent aggression.Neurobiology of stress · 2026Review
- Synaptic density in the hippocampus of depressed patients: A quantitative electron microscopic study.Progress in neuro-psychopharmacology & biological psychiatry · 2026Article
- Decoding the cellular landscape of biological stress in the human brain.Neurobiology of stress · 2026Article
- Astrocytic glutamate regulation is shaped by adversity and glucocorticoid signalling.bioRxiv : the preprint server for biology · 2025Article
- The mediating role of self-compassion in the relationship between childhood trauma and the symptoms of body dysmorphic disorder.BMC psychology · 2025Article
- Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides.Neurobiology of stress · 2025Review
- Cerebrolysin Induces Dendritic Tree Plastic Changes and BDNF Increase in the Amygdala of Male Rats with Maternal Deprivation.Neurochemical research · 2025Article
- Identifying behavior regulatory leverage over mental disorders transcriptomic network hubs toward lifestyle-dependent psychiatric drugs repurposing.Human genomics · 2025Article
- Stress Molecular Signaling in Interaction With Cognition.Biological psychiatry · 2025Review
- Single-Nucleus Transcriptome Profiling of Dorsolateral Prefrontal Cortex: Mechanistic Roles for Neuronal Gene Expression, Including the 17q21.31 Locus, in PTSD Stress Response.The American journal of psychiatry · 2023Article
- Neurotrophic factor-based pharmacological approaches in neurological disorders.Neural regeneration research · 2023Review
- The synaptic hypothesis of schizophrenia version III: a master mechanism.Molecular psychiatry · 2023Review
- Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex.Acta neuropathologica · 2023Article
- Taurine Alleviates Chronic Social Defeat Stress-Induced Depression by Protecting Cortical Neurons from Dendritic Spine Loss.Cellular and molecular neurobiology · 2023Article
- FKBP5 intron 7 methylation is associated with higher anxiety proneness and smaller right thalamus volume in adolescents.Brain structure & function · 2022Article
- Alterations in Astrocytic Regulation of Excitation and Inhibition by Stress Exposure and in Severe Psychopathology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Uncovering microglial pathways driving sex-specific neurobiological effects in stress and depression.Brain, behavior, & immunity - health · 2021Article
- Changes in the Number and Morphology of Dendritic Spines in the Hippocampus and Prefrontal Cortex of the C58/J Mouse Model of Autism.Frontiers in cellular neuroscience · 2021Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Severe stress exposure causes the loss of dendritic spines on cortical pyramidal neurons and induces psychiatric-like symptoms in rodent models. These effects are strongest following early-life stress and are most persistent on apical dendrites. However, the long-term impacts and temporal effects of stress exposure on the human brain remain poorly understood. Using a novel postmortem cohort of psychiatric cases with severe stress experienced in childhood, adulthood, or no severe stress, and matched controls, we aimed to determine the impact of stress timing on pyramidal neuron structure in the human orbitofrontal cortex (OFC). We performed Golgi Cox staining and manually measured the morphology and density of over 22,000 dendritic spines on layer-specific pyramidal neuron apical dendrites. We also quantified glucocorticoid receptor mRNA and protein as a marker of stress dysregulation. Both childhood and adulthood stress were associated with large reductions in mature mushroom spine density (up to 56% loss) in both the superficial (II/III) and deeper layers (V) of the OFC. However, childhood stress caused more substantial reductions to both total and mature mushroom spines. No difference in glucocorticoid receptor mRNA and protein were seen between groups, although both negatively correlated with total spine density within the whole cohort. These findings indicate that severe stress, especially when experienced during childhood, persistently affects the fine morphological properties of neurons in the human OFC. This may impact on cell connectivity in this brain area, and at least partly explain the social and emotional symptoms that originate in the OFC in psychiatric disorders.
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