scholarly journals The vaginal microbiota and innate immunity after local excisional treatment for cervical intraepithelial neoplasia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anita Mitra ◽  
David A. MacIntyre ◽  
Maria Paraskevaidi ◽  
Anna-Barbara Moscicki ◽  
Vishakha Mahajan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Proinflammatory Cytokines ◽  
Premenopausal Women ◽  
Post Treatment ◽  
Vaginal Microbiota ◽  
Healthy Controls ◽  
Normal Cytology ◽  
Prevotella Bivia ◽  
The Impact ◽  
High Diversity

Abstract Background Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. Methods We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Results Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment. Conclusions Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.

scholarly journals The Vaginal Microbiota and Innate Immunity After Local Excisional Treatment for Cervical Intraepithelial Neoplasia

2020 ◽  
Author(s):  
Anita Mitra ◽  
David A MacIntyre ◽  
Maria Paraskevaidi ◽  
Anna-Barbara Moscicki ◽  
Vishakha Mahajan ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Proinflammatory Cytokines ◽  
Premenopausal Women ◽  
Post Treatment ◽  
Vaginal Microbiota ◽  
Healthy Controls ◽  
Normal Cytology ◽  
Prevotella Bivia ◽  
The Impact ◽  
High Diversity

Abstract Background: Vaginal microbiota (VMB) are altered in women with cervical intra-epithelial neoplasia (CIN) and associate with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This interventional study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMPs levels in matched vaginal secretions. Analyses were performed to compare bacterial composition and immune analyte levels before and after CIN excision and in healthy controls.Results: Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV: 21/103, 20% vs 1/39, 3%, p=0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV: 19/103, 20% vs 1/39, 3%, p=0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1 and IL-8 remained significantly elevated pre- (p<0.0001 and p=0.0014 respectively) and post-treatment compared to untreated controls (p<0.0001 and p=0.0035 respectively). Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p<0.0001), however their levels remained lower than controls post-treatment.Conclusions: Women with CIN have increased prevalence of Lactobacillus spp. depleted, high-diversity VMB, proinflammatory cytokines and AMPs than normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.

Quantification of Regulatory/Effector CD4+ T Lymphocytes Pre and Post-Treatment in Patients with Classical Hodgkin Lymphoma in Brazil

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4780-4780
Author(s):  
Joyce M. K. Silva ◽  
Adriana M. Damasco Penna ◽  
Maria Mirtes Sales ◽  
Elma Maria Chaves ◽  
Priscilla Brito Silva ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Post Treatment ◽  
Interleukin 17 ◽  
Healthy Controls ◽  
Malignant Cells ◽  
Classical Hodgkin Lymphoma ◽  
Multicentric Study ◽  
The Impact

Abstract Abstract 4780 Introduction: Epstein-Barr virus (EBV) can be found latently infecting Reed-Sternberg (RS) malignant cells in approximately 50% of classical Hodgkin lymphoma (cHL) patients in Brazil. EBV signaling leads to a disbalance between effector and regulatory CD4 T lymphocytes in the tumor microenvironment, promoting the immune evasion of RS malignant cells. However, little is known about these lymphocytes subpopulations in the peripheral blood of patients with cHL and how treatment can modify this regulatory/effector ratio. In this study, we analyzed the regulatory and effector CD4+ subpopulations in peripheral blood in patients with EBV related and non-related cHL and the impact of treatment on these cells. Material and Methods: This is an open multicentric study and, so far, we included 35 patients from December 2009 to December 2011. Blood was drawn at diagnosis and after completion of treatment (1 to 4 months). Eighteen healthy blood donors volunteers were recruited as controls. Quantification of regulatory and effector T lymphocytes was done by flow cytometry using CD3, CD8, CD4, CD25, Foxp3, GITR, CD127 and interleukin-17 (IL17) antibodies and correlated to phenotypic and clinical parameters in uni- and multivariate models pre and post-treatment. In this study, only cHL patients whose histology could be confirmed and EBV association established were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results: From the 35 cHL patients, 17 were EBV related and 18 EBV non-related. The percentage of CD4+CD25highFoxP3+ and CD4+GITR+ at diagnosis was significantly different from healthy controls (median 1.04 vs 0.26, p=0.02; 4.2 vs 2.2, p=0.003; respectively). CD4+CD127+ T lymphocytes were not different from controls (p=0.3). Additionally, CD4+ T lymphocytes with effector phenotype (CD4+IL17+) were significantly increased in cHL patients compared with controls (0.42 vs 0.13, p<0.001). When we compared pre-treatment values of regulatory and effector CD4+ T lymphocytes with post-treatment values, we did not find any statistical difference. Interestingly, post-treatment values were not statistically different from healthy controls. There was no difference on regulatory and effector CD4+ T lymphocytes in the EBV related and non-related cHL patients. Regarding patient's baseline characteristics, patients with advanced disease and B symptoms presented with increased CD4+CD25highFoxP3+ and CD4+GITR+ T lymphocytes (p=0.03 and p=0.01, respectively). Conclusions: Our results demonstrate that patients with cHL presented with increased CD4+CD25highFoxP3+, CD4+GITR+ and CD4+IL17+ at diagnosis compared with healthy controls. Also, treatment had no impact on these CD4+ T lymphocytes populations. Probably, the moment blood was drawn after completion of therapy could have influenced our results as we know that immunological reconstitution in patients with cHL may take several months. Further studies investigating these CD4+ T lymphocytes subpopulations together with functional assays will contribute not only to our understanding on the pathogenesis of cHL but also to the development of therapeutic strategies designed to manipulate regulatory activity. Given that the incidence of EBV-related cHL, disease presentation and severity are different in developing countries than in developed ones, we emphasize the importance of this ongoing Brazilian multicentric project. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells

2020 ◽  
Vol 117 (48) ◽  
pp. 30639-30648
Author(s):  
Dan Hu ◽  
Emily C. Tjon ◽  
Karin M. Andersson ◽  
Gabriela M. Molica ◽  
Minh C. Pham ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
T Cells ◽  
Transcription Factor ◽  
Proinflammatory Cytokines ◽  
Th17 Cells ◽  
Gene Set Enrichment Analysis ◽  
Aberrant Expression ◽  
Signature Genes ◽  
The Impact

IL-17–producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6+CXCR3−CD45RA−CD4+T (CCR6+T) cells isolated from anti-TNF–treated RA patients classified as responders or nonresponders to therapy. CCR6+T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6+T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targetingUSF2in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.

scholarly journals Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?

2021 ◽  
Author(s):  
Tongtong Zhao ◽  
Kai Zhang ◽  
Yelei Zhang ◽  
Yating Yang ◽  
Xiaoshuai Ning ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Side Effects ◽  
Proinflammatory Cytokines ◽  
Peripheral Blood ◽  
Animal Experiments ◽  
Pancreatic Tissue ◽  
Mouse Serum ◽  
Healthy Controls ◽  
Immunological Mechanisms ◽  
Tnf Α

Abstract Rationale and objective Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. Methods We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. Results Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients’ BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. Conclusion Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.

scholarly journals Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3256
Author(s):  
Adam Brewczyński ◽  
Beata Jabłońska ◽  
Agnieszka Maria Mazurek ◽  
Jolanta Mrochem-Kwarciak ◽  
Sławomir Mrowiec ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Oropharyngeal Cancer ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Post Treatment ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Hpv Status ◽  
Pre Treatment ◽  
The Impact

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.

scholarly journals AB0915 BONE MINERAL DENSITY AND FRACTURE FREQUENCY IN PREMENOPAUSAL WOMEN WITH RHEUMATIC DISEASES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1759.2-1759
Author(s):  
N. Toroptsova ◽  
O. Dobrovolskaya ◽  
O. Nikitinskaya ◽  
N. Demin ◽  
A. Smirnov ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Lumbar Spine ◽  
Serum Vitamin ◽  
Premenopausal Women ◽  
Healthy Controls ◽  
C Reactive Protein ◽  
Mineral Density ◽  
Serum Vitamin D ◽  
Reactive Protein

Background:The onset of the disease in young and middle age is typical for rheumatic diseases (RDS), but most studies on osteoporosis were conducted in patients (pts) older than 50 years, which included postmenopausal women.Objectives:To assess bone mineral density (BMD), fracture frequency and the factors associated with low BMD in premenopausal women with RDs.Methods:160 women (median age, 36 [29; 43] years): 120 pts with RDs (43 rheumatoid arthritis (RA), 53 systemic sclerosis (SSc) and 24 psoriatic arthritis (PsA)) and 40 age-matched healthy controls were enrolled in the study. We performed a dual-energy X-ray absorptiometry (DXA, Hologic Discovery A, USA) to measure BMD in lumbar spine, femoral neck and total hip. BMD decreasing grade was evaluated by the Z-score <-2SD. All pts were interviewed using a unified questionnaire including assessment of daily dietary calcium intake. Serum vitamin D, C-reactive protein and erythrocyte sedimentation rate (ESR) measurements were done.Results:25% pts with RDs and only 8% healthy controls have low BMD (p=0.02). RA, SSc and PsA pts had low BMD in 37%, 21% and 13%, respectively, that was more often than in healthy women (p=0.004, p=0.046 and p= 0.081, respectively). 9,3% RA pts and 7,5% SSc pts had low energy fractures. BMD of RDs pts in all areas of measurement demonstrated a direct correlation with height, weight, body mass index, and serum vitamin D concentration and an inverse correlation with the cumulative dose of glucocorticoids. Also, proximal femur BMD inversely correlated with RDs duration. BMD of femoral neck and total hip inversely correlated with C-reactive protein level in SSc pts. In RA women we found a direct correlation between lumbar spine and femur neck BMD and ESR.Conclusion:25% of premenopausal women with RDs had reduced BMD and needed monitoring and osteoporosis prevention, while 9.3% pts with RA and 7.5% women with SSc needed anti-osteoporotic treatment.Disclosure of Interests:None declared

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

scholarly journals Association between apolipoprotein gene polymorphisms and hyperlipidemia: a meta-analysis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiao-Ning Zhao ◽  
Quan Sun ◽  
You-Qin Cao ◽  
Xiao Ran ◽  
Yu Cao
Keyword(s):  
Risk Factor ◽  
Cerebrovascular Disease ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Control Group ◽  
Case Group ◽  
Healthy Controls ◽  
Ε4 Allele ◽  
Different Populations ◽  
The Impact

Abstract Background Hyperlipidemia plays an important role in the etiology of cardio-cerebrovascular disease. Over recent years, a number of studies have explored the impact of apolipoprotein genetic polymorphisms in hyperlipidemia, but considerable differences and uncertainty have been found in their association with different populations from different regions. Results A total of 59 articles were included, containing in total 13,843 hyperlipidemia patients in the case group and 15,398 healthy controls in the control group. Meta-analysis of the data indicated that APOA5–1131 T > C, APOA1 -75 bp, APOB XbaI, and APOE gene polymorphisms were significantly associated with hyperlipidemia, with OR values of 1.996, 1.228, 1.444, and 1.710, respectively. All P-values were less than 0.05. Conclusions Meta-analysis of the data indicated that the C allele of APOA5 1131 T > C, the A allele at APOA1-75 bp, the APOB XbaI T allele, and the ε2 and ε4 allele of APOE were each a risk factor for susceptibility for hyperlipidemia.

scholarly journals 663 Improved Sleep After a Brief Intervention for Insomnia Mediates Improvements in Depression Symptoms During the COVID-19 Pandemic

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A259-A259
Author(s):  
Kathleen O’Hora ◽  
Mateo Lopez ◽  
Allison Morehouse ◽  
Andrea Cordero ◽  
Raquel Osorno ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Outcome Measures ◽  
Symptom Severity ◽  
Post Treatment ◽  
Symptom Improvement ◽  
Depression Symptoms ◽  
Insomnia Symptom ◽  
The Impact ◽  
Insomnia Symptoms ◽  
Rate Of Improvement

Abstract Introduction The COVID-19 Pandemic and mitigation efforts have led to drastic increases in acute insomnia symptoms, which left untreated may contribute to increased risk for other negative mental health outcomes, including depression. However, the impact of treating acute insomnia symptoms on future depression outcomes remains unknown. Moreover, whether sleep improvements as a result of an insomnia treatment mediate subsequent reduction of depression symptoms similarly remains unknown. Methods At this writing, 44 individuals experiencing insomnia symptoms (Insomnia Severity Index; ISI ≥ 10) that began during the COVID-19 pandemic have been randomized to receive a brief, telehealth Cognitive Behavioral Therapy for Insomnia (CBTI) waitlist control. Treatment was delivered in 4 sessions over a 5-week period. CBTI is the gold-standard behavioral intervention for chronic insomnia and has been applied successfully via telemedicine. Outcome measures were depressive symptoms as measured by the Patient Health Questionnare-9 (PHQ-9) minus the sleep item and insomnia symptom severity as measured by the ISI. Both outcome measures were collected at baseline (week 0), throughout treatment phase (weeks 2–6), and at the post-treatment (week 7). Linear mixed models determined the impact of treatment on depression and insomnia symptom severity. Mediation was tested using the MacArthur framework. Results There was a significant Group x Time interaction, with CBTI leading to a greater rate of improvement in ISI (b = -1.14, p &lt; 0.001) and PHQ-9 (b = -0.61, p = 0.002) than the control. Critically, the rate of improvement in insomnia symptoms to the last session of treatment, was associated with the subsequent improvement in depressive symptoms post-treatment (b = 2.06, p = 0.017). In contrast, depressive symptom improvement was not associated with insomnia symptom improvement (b = 4.28, p = 0.102). Conclusion This preliminary data suggests that brief CBTI can reduce pandemic onset insomnia and other depressive symptoms. The preliminary mediation results further suggest that sleep may be an important treatment target for reducing situational depressive symptoms and supports the need to examine the physiological mechanisms of sleep using high-density EEG in a larger sample. Support (if any):

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