Metabolic-inflammatory status as predictor of clinical outcome at 1-year follow-up in patients with first episode psychosis

Nettis, Maria Antonietta; Pergola, Giulio; Kolliakou, Anna; O’Connor, Jennifer; Bonaccorso, Stefania; David, Anthony S.; Gaughran, Fiona; Forti, Marta Di; Murray, Robin M.; Marques, Tiago Reis; Blasi, Giuseppe; Bertolino, Alessandro; Pariante, Carmine M.; Dazzan, Paola; Mondelli, Valeria

doi:10.1016/j.psyneuen.2018.09.005

Cited by 45 publications

(27 citation statements)

References 46 publications

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“…A multitude of studies and meta-analyses show that patients with major depressive disorder (MDD) have, on average, increased serum levels of pro-inflammatory cytokines, like interleukin 1 beta (IL-1-beta), IL-6 and tumour necrosis factor alpha (TNF-alpha), and of the acute phase protein, C-reactive protein (CRP) 1,2,4,5 . Patients with 'treatment resistant depression' (TRD) are more likely to have increased inflammation 6,7 , as do patients with cardiovascular disorders, obesity, anxiety, and a history of childhood maltreatment 3,[8][9][10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

et al. 2020

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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.

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Section: Introductionmentioning

confidence: 99%

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

et al. 2020

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“…Testing CRP levels in overweight patients with depression could be useful for recommending adjunct anti-inflammatory treatments or predicting their likelihood of developing additional comorbidities in the future. Indeed, several clinical trials have observed that higher BMI at baseline predicted a poorer response to antidepressant treatments (Jha et al, 2018;Uher et al, 2009), while we have previously shown that immune-metabolic status was associated with a poorer response to antipsychotic medication in individuals with psychosis (Nettis et al, 2019). Antiinflammatory drugs improve the therapeutic action of antidepressants (Bai et al, 2020;Haroon, Raison, & Miller, 2012), which could be particularly useful in the context of chronically inflamed overweight patients with depression.…”

Section: Discussionmentioning

confidence: 83%

The influence of comorbid depression and overweight status on peripheral inflammation and cortisol levels

et al. 2021

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Background Depression and overweight are each associated with abnormal immune system activation. We sought to disentangle the extent to which depressive symptoms and overweight status contributed to increased inflammation and abnormal cortisol levels. Methods Participants were recruited through the Wellcome Trust NIMA Consortium. The sample of 216 participants consisted of 69 overweight patients with depression; 35 overweight controls; 55 normal-weight patients with depression and 57 normal-weight controls. Peripheral inflammation was measured as high-sensitivity C-Reactive Protein (hsCRP) in serum. Salivary cortisol was collected at multiple points throughout the day to measure cortisol awakening response and diurnal cortisol levels. Results Overweight patients with depression had significantly higher hsCRP compared with overweight controls (p = 0.042), normal-weight depressed patients (p < 0.001) and normal-weight controls (p < 0.001), after controlling for age and gender. Multivariable logistic regression showed that comorbid depression and overweight significantly increased the risk of clinically elevated hsCRP levels ⩾3 mg/L (OR 2.44, 1.28–3.94). In a separate multivariable logistic regression model, overweight status contributed most to the risk of having hsCRP levels ⩾3 mg/L (OR 1.52, 0.7–2.41), while depression also contributed a significant risk (OR 1.09, 0.27–2). There were no significant differences between groups in cortisol awakening response and diurnal cortisol levels. Conclusion Comorbid depression and overweight status are associated with increased hsCRP, and the coexistence of these conditions amplified the risk of clinically elevated hsCRP levels. Overweight status contributed most to the risk of clinically elevated hsCRP levels, but depression also contributed to a significant risk. We observed no differences in cortisol levels between groups.

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“…A multinational, multi-center, randomized, double-blind study of first-episode psychosis patients showed that those with the most severe symptoms before treatment presented with higher pro-inflammatory compounds and were the most at risk of non-remission compared to psychosis patients with less severe symptoms (Martinuzzi et al, 2019). Additionally, in a longitudinal study of first-episode psychosis patients an association was found between increased high-sensitivity CRP, triglycerides and BMI at baseline, and higher PANSS scores and reduced treatment response at 1-year follow-up (Nettis et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis

et al. 2021

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Background This meta-analysis on peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder (MDD) examined which compounds change following psychopharmacological treatment. Methods The Embase, PubMed and PsycINFO databases were systematically searched for longitudinal studies reporting measurements of blood compounds in drug-naïve first-episode schizophrenia or MDD. Results For this random-effects meta-analysis, we retrieved a total of 31 studies comprising 1818 schizophrenia patients, and 14 studies comprising 469 MDD patients. Brain-derived neurotrophic factor (BDNF) increased following treatment in schizophrenia (Hedges' g (g): 0.55; 95% confidence interval (CI) 0.39–0.70; p < 0.001) and MDD (g: 0.51; CI 0.06–0.96; p = 0.027). Interleukin (IL)-6 levels decreased in schizophrenia (g: −0.48; CI −0.85 to −0.11; p = 0.011), and for MDD a trend of decreased IL-6 levels was observed (g: −0.39; CI −0.87 to 0.09; p = 0.115). Tumor necrosis factor alpha (TNFα) also decreased in schizophrenia (g: −0.34; CI −0.68 to −0.01; p = 0.047) and in MDD (g: −1.02; CI −1.79 to −0.25; p = 0.009). Fasting glucose levels increased only in schizophrenia (g: 0.26; CI 0.07–0.44; p = 0.007), but not in MDD. No changes were found for C-reactive protein, IL-1β, IL-2 and IL-4. Conclusions Psychopharmacological treatment has modulating effects on BDNF and TNFα in drug-naïve first-episode patients with either schizophrenia or MDD. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune dysfunctions.

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Metabolic-inflammatory status as predictor of clinical outcome at 1-year follow-up in patients with first episode psychosis

Cited by 45 publications

References 46 publications

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

Whole-blood expression of inflammasome- and glucocorticoid-related mRNAs correctly separates treatment-resistant depressed patients from drug-free and responsive patients in the BIODEP study

The influence of comorbid depression and overweight status on peripheral inflammation and cortisol levels

Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis

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