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Cited by 67Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

The Fragile Brain: Stress Vulnerability, Negative Affect and GABAergic Neurocircuits in Psychosis

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Taylor, Stephan F, Grove, Tyler B, Ellingrod, Vicki L, Tso, Ivy F·2019·Schizophrenia Bulletin
DOI 10.1093/schbul/sbz046PMC PMC6811817
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Abstract

Persons with schizophrenia exhibit sensitivity to stress and negative affect (NA), both strongly correlated with poor functional outcome. This theoretical review suggests that NA reflects a “fragile brain,” ie, vulnerable to stress, including events not experienced as stressful by healthy individuals. Based on postmortem evidence of altered gamma-aminobutyric acid (GABA) function in parvalbumin positive interneurons (PVI), animal models of PVI abnormalities and neuroimaging data with GABAergic challenge, it is suggested that GABAergic disruptions weaken cortical regions, which leads to stress vulnerability and excessive NA. Neurocircuits that respond to stressful and salient environmental stimuli, such as the hypothalamic-pituitary-adrenal axis and the amygdala, are highly dysregulated in schizophrenia, exhibiting hypo- and hyper-activity. PVI abnormalities in lateral prefrontal cortex and hippocampus have been hypothesized to affect cognitive function and positive symptoms, respectively; in the medial frontal cortex (dorsal anterior cingulate cortex and dorsal medial prefrontal cortex), these abnormalities may lead to vulnerability to stress, NA and dysregulation of stress responsive systems. Given that postmortem PVI disruptions have been identified in other conditions, such as bipolar disorder and autism, stress vulnerability may reflect a transdiagnostic dimension of psychopathology.

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Cited by

Sorted by citations

Authors
Taylor, S. F., Grove, T. B., Ellingrod, V. L., & Tso, I. F.
Affiliations
University of Michigan (US)
Corresponding author
Taylor, Stephan F
ORCID
Venue
Schizophrenia Bulletin
Publisher
Oxford University Press (OUP)
Published
2019-05-31
Volume
45
Issue
6
Pages
1170-1183
ISSN
  • 0586-7614 (ISSN-L)
  • 1745-1701
DOI
10.1093/schbul/sbz046
PMC
PMC6811817
OpenAlex
W2947449697
Cited by
67
References
24
Citations by year
2026: 3 · 2025: 11 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 9 · 2020: 7 · 2019: 2
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Schizophrenia Bulletin (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (MH101676[SFT], MH086701[SFT], MH108823[IFT], MH082784[VE])
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
schizophrenia, stress vulnerability
MeSH terms
Affect, Amygdala, Animals, Brain, Disease Models, Animal, gamma-Aminobutyric Acid, Hippocampus, Humans, Hypothalamo-Hypophyseal System, Interneurons, Neural Pathways, Parvalbumins, Pituitary-Adrenal System, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Stress, Psychological, Prefrontal Cortex

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