ReviewBrain sciences2019
Loss of Prefrontal Cortical Higher Cognition with Uncontrollable Stress: Molecular Mechanisms, Changes with Age, and Relevance to Treatment.
Review in Brain sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 72 citations in OpenAlex.
- A neurodevelopmental model of eating disorder risk in midlife to older adulthood.Neuroscience and biobehavioral reviews · 2026Review
- Dorsolateral Prefrontal Cortex Circuitry at the Intersection of Cognition and Disease.Biological psychiatry · 2026Review
- Review
- Disrupted synapses: prefrontal cortex-reward circuit dysfunction in stress-induced depression-like behaviors.Frontiers in cellular neuroscience · 2026Review
- Inflammatory mechanisms underlying early Alzheimer's disease pathology: evidence from the aging rhesus macaque brain.Frontiers in cellular neuroscience · 2026Review
- Neurobiological subtypes of adolescent depression: a multimodal integration of morphometric similarity network and spatial transcriptomics.Molecular psychiatry · 2025Article
- Low affinity noradrenergic signaling promotes passive coping during reinforcement behavior.bioRxiv : the preprint server for biology · 2025Article
- Investigating whether alcohol is transformed to norepinephrine or dopamine in the mouse brain.Pharmacological reports : PR · 2025Article
- Integrated Gene and Isoform-Level Transcriptomic Analysis of Adverse Childhood Experiences in the Human Prefrontal Cortex.The Yale journal of biology and medicine · 2025Article
- From Stress to Synapse: The Neuronal Atrophy Pathway to Mood Dysregulation.International journal of molecular sciences · 2025Review
- Interaction between emotion lability, emotion regulation and structural brain abnormalities in patients with anorexia nervosa and borderline personality disorder.Frontiers in neuroscience · 2025Article
- Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Threat- and reward-related brain circuitry, perceived stress, and anxiety in adolescents during the COVID-19 pandemic: a longitudinal investigation.Social cognitive and affective neuroscience · 2024Article
- Heightened SAM- and HPA-axis activity during acute stress impairs decision-making: A systematic review on underlying neuropharmacological mechanisms.Neurobiology of stress · 2024Article
- β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction.Neurobiology of stress · 2024Review
- The neurocomputational signature of decision-making for unfair offers in females under acute psychological stress.Neurobiology of stress · 2024Article
- Daily and Ethnic Discriminatory Experiences and Cognitive Control in Mexican-Origin Bilingual Language Brokers.International journal of bilingual education and bilingualism · 2024Article
- Differential Cortical Volume and Surface Morphometry in Youth With Chronic Health Conditions.Biological research for nursing · 2024Article
- Potassium channels in animal models of post-traumatic stress disorder: mechanistic and therapeutic implications.Frontiers in cellular neuroscience · 2024Article
- Stress and Right Prefrontal Transcranial Direct Current Stimulation (tDCS) Interactive Effects on Visual Working Memory and Learning.Brain sciences · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The newly evolved prefrontal cortex (PFC) generates goals for "top-down" control of behavior, thought, and emotion. However, these circuits are especially vulnerable to uncontrollable stress, with powerful, intracellular mechanisms that rapidly take the PFC "off-line." High levels of norepinephrine and dopamine released during stress engage α1-AR and D1R, which activate feedforward calcium-cAMP signaling pathways that open nearby potassium channels to weaken connectivity and reduce PFC cell firing. Sustained weakening with chronic stress leads to atrophy of dendrites and spines. Understanding these signaling events helps to explain the increased susceptibility of the PFC to stress pathology during adolescence, when dopamine expression is increased in the PFC, and with advanced age, when the molecular "brakes" on stress signaling are diminished by loss of phosphodiesterases. These mechanisms have also led to pharmacological treatments for stress-related disorders, including guanfacine treatment of childhood trauma, and prazosin treatment of veterans and civilians with post-traumatic stress disorder.
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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.