In vitro modeling of the neurobiological effects of glucocorticoids: A review

Bassil, Katherine; Krontira, Anthi C.; Lee, Thomas; Escoto, Alana I.H.; Snijders, Clara; Pernia, Cameron D.; Pasterkamp, R. Jeroen; Nijs, Laurence de; Hove, Daniël van den; Kenis, Günter; Boks, Marco P.; Vadodaria, Krishna C.; Daskalakis, Nikolaos; Binder, Elisabeth B.; Rutten, Bart P. F.

doi:10.1016/j.ynstr.2023.100530

Cited by 11 publications

(10 citation statements)

References 215 publications

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“…The recent decade has witnessed a surge in studies of inflammatory biomarkers associated with psychiatric disorders. This growing body of evidence has undeniably enhanced our understanding of the mechanisms underlying mental disorders: inflammation is now known to be intertwined with glucocorticoid neurotoxicity, microglia activation, and neurogenesis ( 29 , 30 ; https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)01715-2/fulltext#:~:text=Indeed%2C%20biomarkers%20of%20inflammation%20such,responses%20and%20poor%20clinical%20outcomes ); however, the clinical utility of inflammatory markers is yet to be established.…”

Section: Discussionmentioning

confidence: 99%

Risk assessment of psychiatric complications in infectious diseases: CALCulation of prognostic indices on example of COVID-19

Sorokin,

Markin,

Trufanov

et al. 2024

Front. Psychiatry

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IntroductionFactors such as coronavirus neurotropism, which is associated with a massive increase in pro-inflammatory molecules and neuroglial reactivity, along with experiences of intensive therapy wards, fears of pandemic, and social restrictions, are pointed out to contribute to the occurrence of neuropsychiatric conditions.AimThe aim of this study is to evaluate the role of COVID-19 inflammation-related indices as potential markers predicting psychiatric complications in COVID-19.MethodsA total of 177 individuals were examined, with 117 patients from a temporary infectious disease ward hospitalized due to COVID-19 forming the experimental group and 60 patients from the outpatient department showing signs of acute respiratory viral infection comprising the validation group. The PLR index (platelet-to-lymphocyte ratio) and the CALC index (comorbidity + age + lymphocyte + C-reactive protein) were calculated. Present State Examination 10, Hospital Anxiety and Depression Scale, and Montreal Cognitive Assessment were used to assess psychopathology in the sample. Regression and Receiver operating characteristic (ROC) analysis, establishment of cutoff values for the COVID-19 prognosis indices, contingency tables, and comparison of means were used.ResultsThe presence of multiple concurrent groups of psychopathological symptoms in the experimental group was associated (R² = 0.28, F = 5.63, p < 0.001) with a decrease in the PLR index and a simultaneous increase in CALC. The Area Under Curve (AUC) for the cutoff value of PLR was 0.384 (unsatisfactory). For CALC, the cutoff value associated with an increased risk of more psychopathological domains was seven points (sensitivity = 79.0%, specificity = 69.4%, AUC = 0.719). Those with CALC > 7 were more likely to have disturbances in orientation (χ² = 13.6; p < 0.001), thinking (χ² = 7.07; p = 0.008), planning ability (χ² = 3.91; p = 0.048). In the validation group, an association (R²McF = 0.0775; p = 0.041) between CALC values exceeding seven points and the concurrent presence of pronounced anxiety, depression, and cognitive impairments was demonstrated (OR = 1.52; p = 0.038; AUC = 0.66).DiscussionIn patients with COVID-19, the CALC index may be used for the risk assessment of primary developed mental disturbances in the context of the underlying disease with a diagnostic threshold of seven points.

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Section: Discussionmentioning

confidence: 99%

Risk assessment of psychiatric complications in infectious diseases: CALCulation of prognostic indices on example of COVID-19

Sorokin,

Markin,

Trufanov

et al. 2024

Front. Psychiatry

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“…High concentrations of GC can also affect many neurotransmitter systems. MDD and PTSD are characterized by a noradrenergic system that is associated with stress-related affective disorders like MDD and PTSD 37 , 41 . It has been documented that GCs can reverse the effects of β-adrenergic signaling 41 .…”

Section: Discussionmentioning

confidence: 99%

“…MDD and PTSD are characterized by a noradrenergic system that is associated with stress-related affective disorders like MDD and PTSD 37 , 41 . It has been documented that GCs can reverse the effects of β-adrenergic signaling 41 . The 5-HT1A receptor is crucial for the pathogenesis and treatment of depression associated with the HPA axis, as supported by a large amount of evidence 42 .…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between depression and the HPA axis has been widely discussed, with more than 40-60% of depression patients having hypercortisolism or HPA-axis dysregulation 45 . Neurotransmitter systems affected by HPA-axis dysregulation, as described above, may alter the patient's physical and mental condition and lead to emotional disorders such as depression, such as the transmission of serotonin (5-HT) and norepinephrine (NE) 41 . Additionally, studies have proven that individuals with Cushing's syndrome-induced elevated GC may exhibit emotional symptoms 46 .…”

Section: Discussionmentioning

confidence: 99%

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Depression risk in chronic tonsillitis patients underwent tonsillectomy: a global federated health network analysis

Chang,

Lu,

Guo

et al. 2024

Int. J. Med. Sci.

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Background: Tonsillectomy is a common surgery in the US, with possible postoperative complications. While small studies indicate postoperative depressive symptoms may occur, large-scale evidence is lacking on the tonsillectomy-depression link. Methods: We conducted a retrospective cohort study using the TriNetX US collaborative network, offering de-identified electronic health data from 59 collaborative healthcare organizations (HCOs) in the United States. In this study, people being diagnosed of chronic tonsillitis between January 2005 and December 2017 were enrolled. Patients deceased, with previous record of cancers or psychiatric events before index date were excluded. 14,874 chronic tonsillitis patients undergoing tonsillectomy were propensity score matched 1:1 to controls for age, sex, and race. New-onset depression risks were evaluated over 5 years post-tonsillectomy and stratified by age and sex. Confounders were adjusted for including demographics, medications, comorbidities and socioeconomic statuses. Results: After matching, the difference of key baseline characteristics including age, sex, comedications status and obesity status was insignificant between tonsillectomy and non-tonsillectomy groups. Tonsillectomy had a 1.29 times higher 5-year depression risk versus matched controls (95% CI, 1.19-1.40), with elevated risks seen at 1 year (HR=1.51; 95% CI, 1.28-1.79) and 3 years (HR=1.30; 95% CI, 1.18-1.43). By stratifications, risks were increased for both males (HR=1.30; 95% CI, 1.08-1.57) and females (HR=1.30; 95% CI, 1.18-1.42), and significantly higher in ages 18-64 years (HR=1.37; 1.26-1.49), but no significance observed for those 65 years and older. After performing sensitivity analyses and applying washout periods of 6, 12, and 36 months, the outcome remained consistent with unadjusted results. Conclusion: This real-world analysis found tonsillectomy was associated with a 30% higher 5-year depression risk versus matched non-tonsillectomy patients with chronic tonsillitis. Further mechanistic research is needed to clarify the pathophysiologic association between depression and tonsillectomy. Depression is not commonly mentioned in the current post-tonsillectomy care realm; however, the outcome of our study emphasized the possibility of these suffering condition after operation. Attention to psychological impacts following tonsillectomy is warranted to support patient well-being, leading to better management of post-tonsillectomy individuals.

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“…Despite the strong evidence for harmful effects from epidemiological studies, there is limited evidence on the underlying molecular and cellular mechanisms 11,21 . Using human neural organoids as models of early brain development, we could recently show that GCs elicit cell-type specific transcriptional responses and that there is a highly significant enrichment of genes associated with neurodevelopmental delay, ASD, and more common psychiatric disorders among those regulated by GCs, especially in neurons 22 .…”

Section: Introductionmentioning

confidence: 99%

Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids

Dony,

Krontira,

Kaspar

et al. 2024

Preprint

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Disruptions in the tightly regulated process of human brain development have been linked to increased risk for brain and mental illnesses. While the genetic contribution to these diseases is well established, important environmental factors have been less studied at molecular and cellular levels. In this study, we used single-cell and cell-type-specific techniques to investigate the effect of glucocorticoid (GC) exposure, a mediator of antenatal environmental risk, on gene regulation and lineage specification in unguided human neural organoids. We characterized the transcriptional response to chronic GC exposure during neural differentiation and studied the underlying gene regulatory networks by integrating single-cell transcriptomics- with chromatin accessibility data. We found lasting cell type-specific changes that included autism risk genes and several transcription factors associated with neurodevelopment. Chronic GCs influenced lineage specification primarily by priming the inhibitory neuron lineage through key transcription factors like PBX3. We provide evidence for convergence of genetic and environmental risk factors through a common mechanism of altering lineage specification.

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In vitro modeling of the neurobiological effects of glucocorticoids: A review

Cited by 11 publications

References 215 publications

Risk assessment of psychiatric complications in infectious diseases: CALCulation of prognostic indices on example of COVID-19

Risk assessment of psychiatric complications in infectious diseases: CALCulation of prognostic indices on example of COVID-19

Depression risk in chronic tonsillitis patients underwent tonsillectomy: a global federated health network analysis

Chronic exposure to glucocorticoids amplifies inhibitory neuron cell fate during human neurodevelopment in organoids

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