The DOI matches its Crossref record; 261 of the 261 references it cites were found in a registry or an index.
Molecular mechanisms of stress-induced prefrontal cortical impairment: Implications for mental illness
Open accessAbstract
The symptoms of mental illness often involve weakened regulation of thought, emotion, and behavior by the prefrontal cortex. Exposure to stress exacerbates symptoms of mental illness and causes marked prefrontal cortical dysfunction. Studies in animals have revealed the intracellular signaling pathways activated by stress exposure that induce profound prefrontal cortical impairment: Excessive dopamine stimulation of D1 receptors impairs prefrontal function via cAMP intracellular signaling, leading to disconnection of prefrontal networks, while excessive norepinephrine stimulation of α1 receptors impairs prefrontal function via phosphatidylinositol–protein kinase C intracellular signaling. Genetic studies indicate that the genes disrupted in serious mental illness (bipolar disorder and schizophrenia) often encode for the intracellular proteins that serve as brakes on the intracellular stress pathways. For example, disrupted in schizophrenia 1 (DISC1) normally regulates cAMP levels, while regulator of G protein signaling 4 (RGS4) and diacylglycerol kinase (DGKH)—the molecule most associated with bipolar disorder— normally serve to inhibit phosphatidylinositol–protein kinase C intracellular signaling. Patients with mutations resulting in loss of adequate function of these genes likely have weaker endogenous regulation of these stress pathways. This may account for the vulnerability to stress and the severe loss of PFC regulation of behavior, thought, and affect in these illnesses. This review highlights the signaling pathways onto which genetic vulnerability and stress converge to impair PFC function and induce debilitating symptoms such as thought disorder, disinhibition, and impaired working memory.
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“depression and anxiety, substance use, intimate partner violence, body image concerns, and sexual compulsivity could be argued to represent final behavioral outcomes of the same or similar underlying neurological, cognitive, affective, and interpersonal stress pathways”
From A transdiagnostic minority stress treatment approach for gay and bisexual men's syndemic health conditions (2015) · cites this paper as Hains & Arnsten, 2008
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Control of goal-directed and stimulus-driven attention in the brain
Corbetta, M., & Shulman, G. L. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn755 · Cited by 12,881
An Integrative Theory of Prefrontal Cortex Function
Miller, E. K., & Cohen, J. D. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.167 · Cited by 12,803
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
Conflict monitoring and cognitive control
Botvinick, M. M., Braver, T. S., Barch, D. M., Carter, C. S., & Cohen, J. D. (2001) · Psychological Review · doi:10.1037/0033-295x.108.3.624 · Cited by 7,351
Cognitive and emotional influences in anterior cingulate cortex
Bush, G., Luu, P., & Posner, M. I. (2000) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(00)01483-2 · Cited by 6,259
Aston-Jones, G., & Cohen, J. D. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135709 · Cited by 4,472
Anterior Cingulate Cortex, Error Detection, and the Online Monitoring of Performance
Carter, C. S., Braver, T. S., Barch, D. M., Botvinick, M. M., Noll, D., & Cohen, J. D. (1998) · Science · doi:10.1126/science.280.5364.747 · Cited by 3,273
Inhibition and the right inferior frontal cortex
Aron, A. R., Robbins, T. W., & Poldrack, R. A. (2004) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2004.02.010 · Cited by 3,197
The Wellcome Trust Case Control Consortium, U.K.
Mossman, K. (2008) · Scientific American · doi:10.1038/scientificamerican0108-42a · Cited by 2,714
Cellular basis of working memory
Goldman-Rakic, P. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90304-6 · Cited by 2,663
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Research works printed but not linked: 2
- American Psychological Association (2000) Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV) (American Psychiatric Press, Inc. Washington, DC).
- 10.1162/jocn.2008.20.3.447 · DOI
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Wang, X., Sun, X., Zhou, H.-C., & Luo, F. (2021) · Scientific Reports · doi:10.1038/s41598-021-97769-4 · Cited by 4
Liang, Z. (2021) · Frontiers in Computer Science · doi:10.3389/fcomp.2021.774949 · Cited by 4
Mitsi, V., Ruiz, A., Polizu, C., Farzinpour, Z., Ramakrishnan, A., Serafini, R. A., Parise, E. M., Floodstrand, M., Sial, O. K., Gaspari, S., et al. (2024) · Molecular Pharmacology · doi:10.1124/molpharm.123.000753 · Cited by 5
Sun, X., Wang, X., Zhou, H.-C., Zheng, J., Su, Y.-X., & Luo, F. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113417 · Cited by 4
Comparison between the Effects of Acute Physical and Psychosocial Stress on Feedback-Based Learning
Yang, X., Nackley, B., & Friedman, B. H. (2023) · Brain Sciences · doi:10.3390/brainsci13081127 · Cited by 3
Yuan, J., Zhong, Y., Li, Y., Liao, Y., & Tang, H. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1519492 · Cited by 3
Alzheimer’s Dementia and Lifestyle: Towards a Primary Prevention
Walach, H., & Loef, M. (2013) · Springer eBooks · doi:10.1007/978-1-4614-6852-3_12 · Cited by 2
Role of Prefrontal Cortex Dopamine and Noradrenaline Circuitry in Addiction
Carboni, E., Cadeddu, R., & Rosa, A. (2012) · InTech eBooks · doi:10.5772/51221 · Cited by 1
Vosmer, S. (2012) · Group Analysis · doi:10.1177/0533316412462526 · Cited by 1
Epigenetics, Stress, and Their Potential Impact on Brain Network Function
Diwadkar, V. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800951-2.00015-7 · Cited by 1
Tobacco pharming. A quest to turn the killer crop into a treatment for cancer.
Powledge, T. M. (2001) · PubMed · Cited by 1
Involvement of epigenetic mechanisms in the development of posttraumatic stress disorder
Zupanc, T., Pregelj, P., & Paska, A. V. (2012) · Slovenian Medical Journal
Araujo, O. A. D., & Folha, C. (2013)
Neuronal Mechanisms and Voluntary Agency
Runyan, J. D. (2013) · Palgrave Macmillan eBooks · doi:10.1057/9781137329493_7
Mutant and Transgenic Tools in Modeling Schizophrenia
Desbonnet, L., Tomiyama, K., Koshikawa, N., O’Tuathaigh, C. M. P., & Waddington, J. L. (2009) · Neuromethods · doi:10.1007/978-1-60761-474-6_12
Depression and Cognitive Control in the Face of Negative Information or Stressors
Kaiser, R. H. (2012) · CU Scholar (University of Colorado Boulder)
Effect of unexpected stressor duration on the expression of stress response habituation
Ramsey, R. E. (2011) · CU Scholar (University of Colorado Boulder)
Bjornson, K. J., Vanderplow, A. M., Yang, Y., Kermath, B. A., & Cahill, M. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.03.547282
Xiao, Q., Shen, L., Wang, L., Zhang, S., Wen, S., Ma, Y., Liu, Y., & Xu, B. (2026) · Psychiatry Research · doi:10.1016/j.psychres.2026.117437
Yamamuro, K., Yamauchi, T., & Makinodan, M. (2026) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2026.1915506
Histopathological foundations of behavioral and psychosomatic disorders in animals
Shmayun, S., Утеченко, М. В., Koziy, R., Порошинська, О. А., Huralska, S., Кот, Т. Ф., Yevtukh, L. H., Khomenko, Z., Буднік, Т. С., Leno, Y., et al. (2026) · Regulatory Mechanisms in Biosystems · doi:10.15421/0226140
Metadata
- Authors
- Hains, A. B., & Arnsten, A. F. T.
- Affiliations
- Yale University (US)
- ORCID
- Arnsten, Amy F.T.
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2008-08
- Volume
- 15
- Issue
- 8
- Pages
- 551-564
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- OpenAlex
- W2137006544
- Cited by
- 127
- References
- 261
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 3 · 2017: 7 · 2016: 11 · 2015: 6 · 2014: 9 · 2013: 10 · 2012: 10
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (U54RR024350)
- National Institute on Alcohol Abuse and Alcoholism (RL1AA017536)
- National Institute of Mental Health (P50MH068789)
- National Center for Research Resources (U54RR024350-01)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- prefrontal cortex, stress, mental illness, dopamine D1 receptor, cAMP signaling, DISC1, RGS4, diacylglycerol kinase, bipolar disorder, schizophrenia, genetic susceptibility, working memory, disinhibition, thought disorder, stress-induced cognitive impairment
- MeSH terms
- Animals, Mental Disorders, Humans, Stress, Physiological, Signal Transduction, Prefrontal Cortex
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