ORCID Profile
0000-0001-8690-6839
Current Organisations
King's College London
,
King's College London Institute of Psychiatry Psychology & Neuroscience
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Publisher: Oxford University Press (OUP)
Date: 02-2016
Publisher: Elsevier BV
Date: 12-2023
Publisher: Cold Spring Harbor Laboratory
Date: 18-07-2019
DOI: 10.1101/706309
Abstract: Depression has been associated with increased inflammatory proteins but changes in circulating immune cells are less well defined. We used multi-parametric flow cytometry to investigate 14 subsets of peripheral blood cells in 206 cases of major depressive disorder (MDD) and 77 age- and sex-matched controls. There were significant case-control differences, by univariate and multivariate analysis: cases showed increased immune cell counts, especially neutrophils, CD4 + T cells and monocytes, and increased inflammatory proteins (C-reactive protein and interleukin-6). Within-group analysis demonstrated significant association between the severity of depressive symptoms and increased myeloid and CD4 + cell counts. MDD cases could be partitioned into two groups by forced binary clustering of cell counts: the inflamed depression group (N=81 out of 206 39%) had increased monocyte, CD4 + and neutrophil counts, increased C-reactive protein (CRP) and interleukin 6 (IL-6), and was more depressed than the uninflamed majority of cases. Relaxing the presumption of a binary classification, data-driven clustering identified four subgroups of MDD cases: two of these subgroups (N=38 and N=100 67% collectively) were associated with increased inflammatory proteins and more severe depression, but differed from each other in the relative weighting of myeloid and lymphoid cell counts. Case-control and within-group results were robust to statistical control for the potentially confounding effects of age, sex, BMI, recent infection status, and tobacco use. Peripheral blood immunophenotyping can be used to identify a candidate cellular biomarker of inflamed depression, and to further decompose that binary partition, suggesting that there is more than one mechanistic pathway underlying inflamed depression. Two subgroups of depressed cases (about two-thirds of all 206 cases) were identified by peripheral blood biomarker evidence of distinctive cellular immunophenotypes, biased towards the myeloid or lymphoid lineages in different subgroups, but consistently associated with increased blood concentrations of inflammatory proteins and greater severity of depressive symptoms.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 23-07-2020
DOI: 10.1038/S41398-020-00874-7
Abstract: The mRNA expression signatures associated with the ‘pro-inflammatory’ phenotype of depression, and the differential signatures associated with depression subtypes and the effects of antidepressants, are still unknown. We examined 130 depressed patients (58 treatment-resistant, 36 antidepressant-responsive and 36 currently untreated) and 40 healthy controls from the BIODEP study, and used whole-blood mRNA qPCR to measure the expression of 16 candidate mRNAs, some never measured before: interleukin ( IL)-1-beta , IL-6 , TNF-alpha , macrophage inhibiting factor ( MIF ), glucocorticoid receptor ( GR ), SGK1 , FKBP5 , the purinergic receptor P2RX7 , CCL2 , CXCL12 , c-reactive protein ( CRP ), alpha-2-macroglobulin ( A2M ), acquaporin-4 ( AQP4 ), ISG15 , STAT1 and USP-18 . All genes but AQP4 , ISG15 and USP-18 were differentially regulated. Treatment-resistant and drug-free depressed patients had both increased inflammasome activation (higher P2RX7 and proinflammatory cytokines/chemokines mRNAs expression) and glucocorticoid resistance (lower GR and higher FKBP5 mRNAs expression), while responsive patients had an intermediate phenotype with, additionally, lower CXCL12 . Most interestingly, using binomial logistics models we found that a signature of six mRNAs ( P2RX7 , IL-1-beta, IL-6 , TNF-alpha, CXCL12 and GR ) distinguished treatment-resistant from responsive patients, even after adjusting for other variables that were different between groups, such as a trait- and state-anxiety, history of childhood maltreatment and serum CRP. Future studies should replicate these findings in larger, longitudinal cohorts, and test whether this mRNA signature can identify patients that are more likely to respond to adjuvant strategies for treatment-resistant depression, including combinations with anti-inflammatory medications.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Springer Science and Business Media LLC
Date: 03-05-2016
DOI: 10.1038/TP.2016.68
Publisher: Springer Science and Business Media LLC
Date: 15-01-2013
DOI: 10.1038/TP.2012.138
Publisher: Elsevier BV
Date: 09-2014
Publisher: Royal College of Psychiatrists
Date: 17-04-2023
DOI: 10.1192/BJO.2023.36
Abstract: There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders. MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367. The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis diet duration: 2 weeks to 3 years n = 389 age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some in iduals. Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2022
Publisher: Elsevier BV
Date: 2022
Publisher: Oxford University Press (OUP)
Date: 16-11-2013
DOI: 10.1093/BRAIN/AWT310
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.BIOPSYCH.2019.11.017
Abstract: Depression has been associated with increased inflammatory proteins, but changes in circulating immune cells are less well defined. We used multiparametric flow cytometry to count 14 subsets of peripheral blood cells in 206 depression cases and 77 age- and sex-matched controls (N = 283). We used univariate and multivariate analyses to investigate the immunophenotypes associated with depression and depression severity. Depression cases, compared with controls, had significantly increased immune cell counts, especially neutrophils, CD4 Peripheral immune cell counts were used to distinguish inflamed and uninflamed subgroups of depression and to indicate that there may be mechanistically distinct subgroups of inflamed depression.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Valeria Mondelli.