Much ado about much: Stress, dynamic biomarkers and HPA axis dysregulation along the trajectory to psychosis

Shah, Jai; Malla, Ashok

doi:10.1016/j.schres.2015.01.010

Cited by 60 publications

(49 citation statements)

References 138 publications

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“…136,137 The latter is more associated with fast, short-term responses to stress, whereas the former has been the focus of most of the stress research in schizophrenia. 22,[138][139][140][141][142][143] The HPA axis involves multiple levels of control and feedback, most easily studied by measuring the major secretagogue of the adrenal cortex, cortisol. Schizophrenia shows a complex picture of a dysregulated system.…”

Section: Stress Response Systems In Schizophreniamentioning

confidence: 99%

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

Taylor

Grove

Ellingrod

et al. 2019

Schizophrenia Bulletin

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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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Section: Stress Response Systems In Schizophreniamentioning

confidence: 99%

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

Taylor

Grove

Ellingrod

et al. 2019

Schizophrenia Bulletin

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show abstract

“…With regard to stress biomarkers, there is evidence that CHR subjects manifest heightened basal cortisol (Carol & Mittal, 2015; Karanikas & Garyfallos, 2015; Shah & Malla, 2015). Another recent report on the first-half cohort from NAPLS-2, again with subjects ranging from 13 to 30 years, indicated that both HCs and CHR subjects manifested an age-related increase in cortisol through this period (Walker et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis

Moskow

Addington

Bearden

et al. 2016

Schizophrenia Research

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BACKGROUND Prodromal syndromes often begin in adolescence – a period of neurodevelopmental changes and heightened stress sensitivity. Research has shown elevated stress and cortisol in individuals at clinical high risk (CHR) for psychosis. This cross-sectional study examined relations of age and pubertal status with cortisol and self-reported stress in healthy controls (HCs) and CHR adolescents. It was hypothesized that the relations of age and pubertal stage with cortisol and stress would be more pronounced in CHR youth. METHODS Participants were 93 HCs and 348 CHR adolescents from the North American Prodrome Longitudinal Study (NAPLS). At baseline, measures of stress (Daily Stress Inventory – DSI), Tanner stage (TS), and salivary cortisol were obtained. RESULTS ANCOVA revealed increased DSI scores with age for both groups, and higher DSI scores in CHR adolescents than HCs, with a more pronounced difference for females. Contrary to prediction, with age controlled, HCs showed greater TS-related DSI increases. Analysis of cortisol showed no significant interactions, but a main effect of age and a trend toward higher cortisol in the CHR group. Correlations of cortisol with TS were higher in HC than CHR group. CONCLUSIONS Stress measures increased with age in HC and CHR adolescents, and DSI scores also increased with TS in HCs. The results do not support a more pronounced age or TS increase in stress measures in CHR adolescents, but instead suggest that stress indices tend to be elevated earlier in adolescence in the CHR group. Potential determinants of findings and future directions are discussed.

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“…13, 27 (ii) Second, dysregulation of the hypothalamic–pituitary–adrenal axis might be linked to impaired functioning of the GSH antioxidant defense system. Indeed, in schizophrenia, chronic hyperactivation of the hypothalamic–pituitary–adrenal axis can be observed (for a review and meta-analyses, see refs 28, 29, 30). Plasma cortisol levels, which reflect the activity of the hypothalamic–pituitary–adrenal axis have also been shown to be increased in UHR Individuals, 31, 32, 33 especially in UHR-T. 34 Prolonged increase of cortisol secretion generally reflects a state of chronic stress that, in turn, might lead to increased oxidative stress as reflected by increased reactive oxygen species levels (meta-analysis by Costantini et al 35 ).…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte glutathione levels as long-term predictor of transition to psychosis

et al. 2017

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A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis. The aim of this study was to determine the predictive value of erythrocyte GSH levels on the transition to psychosis in individuals at risk of developing the illness. Erythrocyte GSH levels were measured in 36 at-risk individuals, 15 of whom had transitioned to psychosis at the 7-year follow-up. Univariate Cox regression analysis showed that transition to psychosis at the 7-year time point was significantly associated with low GSH levels at baseline. The area under the receiving operating characteristic curve was 0.819, indicating that GSH can be considered a good predictor of outcome. Although these results need to be replicated, adding the criterion ‘low erythrocyte GSH' to the set of criteria used to identify individuals at risk of psychosis may be indicated.

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Much ado about much: Stress, dynamic biomarkers and HPA axis dysregulation along the trajectory to psychosis

Cited by 60 publications

References 138 publications

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

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

The relations of age and pubertal development with cortisol and daily stress in youth at clinical risk for psychosis

Erythrocyte glutathione levels as long-term predictor of transition to psychosis

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