ReviewChronic stress (Thousand Oaks, Calif.)
Chronic Stress Weakens Connectivity in the Prefrontal Cortex: Architectural and Molecular Changes.
Review in Chronic stress (Thousand Oaks, Calif.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Neurobiological insights into perinatal depression: a multi-dimensional integration of brain structure, function, and metabolism.Frontiers in psychiatry · 2026Pooled it
- Cumulative trauma, neural circuits, and burnout: an integrative model of healthcare worker post-traumatic stress syndromes.European journal of psychotraumatology · 2026Review
- Advances in calcium signalling research for the diagnosis and treatment of depression.Annals of medicine · 2026Review
- Stress, needs, and behaviour: understanding chronic stress in pet domestic dogs (Canis lupus familiaris) from the prism of needs.Biological reviews of the Cambridge Philosophical Society · 2026Review
- NeuronaleNeuro · 2026Article
- Cytokine-mediated immune-to-brain signaling in neural circuit disorders.Experimental & molecular medicine · 2026Review
- Seeing Through Feeling: Dynamic Interplay Between Emotion and Visual Perception.Brain sciences · 2026Review
- Structural determinants of psychological distress in Black mothers: a comparative analysis of maternal filicide.Archives of women's mental health · 2026Article
- Multiplexed changes in synaptic transmission underlie stress-induced reduction of persistent firing in the parietal cortex.Progress in neurobiology · 2026Article
- Violence exposure moderates stress-elicited neurobehavioral function in young people.Emotion (Washington, D.C.) · 2026Article
- A human-derived Bacteroides strain attenuates depressive-like behavior in a rat model of social defeat-induced stress.BMC medicine · 2026Article
- Early life stress-induced depression reveals distinct region-specific modulation of unfolded protein response genes in the prefrontal cortex and hippocampus of rats.Frontiers in psychiatry · 2026Article
- Efficacy of Venlafaxine and Deep Brain Stimulation Against the Effects of Hippocampal Lesion with Ibotenic Acid in Animals Exposed to the Chronic Mild Stress Model of Depression.Current neuropharmacology · 2026Article
- Mechanistic insights into combined prefrontal tDCS and vagal nerve stimulation for stress regulation.Frontiers in psychology · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Disrupted synapses: prefrontal cortex-reward circuit dysfunction in stress-induced depression-like behaviors.Frontiers in cellular neuroscience · 2026Review
- Prefrontal spine loss in neuropsychiatric disorders: circuit consequences for cognition.Frontiers in psychiatry · 2026Review
- Quantitative reconstruction of neuronal mitochondrial network in neurites and somata in rat hippocampus and prefrontal cortex.Frontiers in physiology · 2026Article
- Exploring the effects of short-term forest bathing on anxious medical undergraduates' stressful emotions using near-infrared functional brain imaging and facial expression technology.Frontiers in psychology · 2026Article
- The cortisol axis and psychiatric disorders: an updated review.Pharmacological reports : PR · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic exposure to uncontrollable stress causes loss of spines and dendrites in the prefrontal cortex (PFC), a recently evolved brain region that provides top-down regulation of thought, action, and emotion. PFC neurons generate top-down goals through recurrent excitatory connections on spines. This persistent firing is the foundation for higher cognition, including working memory, and abstract thought. However, exposure to acute uncontrollable stress drives high levels of catecholamine release in the PFC, which activates feedforward calcium-cAMP signaling pathways to open nearby potassium channels, rapidly weakening synaptic connectivity to reduce persistent firing. Chronic stress exposures can further exacerbate these signaling events leading to loss of spines and resulting in marked cognitive impairment. In this review, we discuss how stress signaling mechanisms can lead to spine loss, including changes to BDNF-mTORC1 signaling, calcium homeostasis, actin dynamics, and mitochondrial actions that engage glial removal of spines through inflammatory signaling. Stress signaling events may be amplified in PFC spines due to cAMP magnification of internal calcium release. As PFC dendritic spine loss is a feature of many cognitive disorders, understanding how stress affects the structure and function of the PFC will help to inform strategies for treatment and prevention.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.