Activation of the innate immune system is commonly associated with depression. Immunomodulatory drugs may have efficacy for depressive symptoms that are co-morbidly associated with inflammatory ...disorders. We report a large-scale re-analysis by standardized procedures (mega-analysis) of patient-level data combined from 18 randomized clinical trials conducted by Janssen or GlaxoSmithKline for one of nine disorders (N = 10,743 participants). Core depressive symptoms (low mood, anhedonia) were measured by the Short Form Survey (SF-36) or the Hospital Anxiety and Depression Scale (HADS), and participants were stratified into high (N = 1921) versus low-depressive strata based on baseline ratings. Placebo-controlled change from baseline after 4-16 weeks of treatment was estimated by the standardized mean difference (SMD) over all trials and for each subgroup of trials targeting one of 7 mechanisms (IL-6, TNF-α, IL-12/23, CD20, COX2, BLγS, p38/MAPK14). Patients in the high depressive stratum showed modest but significant effects on core depressive symptoms (SMD = 0.29, 95% CI 0.12-0.45) and related SF-36 measures of mental health and vitality. Anti-IL-6 antibodies (SMD = 0.8, 95% CI 0.20-1.41) and an anti-IL-12/23 antibody (SMD = 0.48, 95% CI 0.26-0.70) had larger effects on depressive symptoms than other drug classes. Adjustments for physical health outcome marginally attenuated the average treatment effect on depressive symptoms (SMD = 0.20, 95% CI: 0.06-0.35), but more strongly attenuated effects on mental health and vitality. Effects of anti-IL-12/23 remained significant and anti-IL-6 antibodies became a trend after controlling for physical response to treatment. Novel immune-therapeutics can produce antidepressant effects in depressed patients with primary inflammatory disorders that are not entirely explained by treatment-related changes in physical health.
Tauroursodeoxycholic acid (TUDCA) has been known for its roles in enhancing cell proliferation and reducing apoptosis in cardiomyocytes proposing it as a valuable treatment approach putatively ...especially in the context of stress-induced cardiovascular dysfunction. In this study, we (1) investigated the detrimental effects of stress on both cell proliferation and apoptosis in cardiomyocytes, and subsequently (2) assess the role of TUDCA in preventing these detrimental changes.
AC16 cardiomyocytes were treated with cortisol 100μM alone or in combination with bile acids TUDCA (10-100μM) for 24hours. Immunocytochemistry was then performed to identify changes in proliferation (with the marker Ki67) and cell apoptosis (with the marker caspase 3 (CC3)).
Results show that cortisol significantly decreased the number of Ki67+ cells (cortisol vs control: -12%, p<0.001) and increased the number of CC3+ cells (cortisol vs control: +9%, p<0.01). Interestingly, treatment with TUDCA (both 10 and 100μM) fully prevented cortisol-induced reduction in Ki67+ cells (cortisol + 10 or 100μM TUDCA vs cortisol: +14%, p<0.001, for both), while treatment with TUDCA (only 10μM) fully prevented cortisol-induced increase in CC3+ cells (cortisol + 10μM TUDCA vs cortisol: -8%, p<0.01).
Overall, our results suggest that cortisol can reduce proliferation and increase apoptosis in cardiomyocytes, and that TUDCA can prevent these detrimental changes.
This work is supported by the European Union’s Horizon 2020 research and innovation programme (grant n° 848158).
Anhedonia is a key symptom of major depressive disorder (MDD) and comprises behavioural deficits in three reward processing subtypes: reward liking, reward wanting, and reward learning. However, ...neuroimaging findings regarding the neural abnormalities underpinning these deficits are complex. We have conducted a systematic review to update, reframe and summarize neuroimaging findings across the three subtypes of anhedonia in MDD. Using PubMed, The Cochrane Library, PsycINFO, and Web of Science databases, we identified 59 fMRI studies comparing participants with current or remitted MDD with controls, using reward processing tasks. For reward liking and wanting, striatal hypoactivation was observed, alongside hypoactivation and hyperactivation across frontal regions. For reward learning, blunted frontostriatal sensitivity to positive feedback was observed. These findings highlight the importance of studying anhedonia not only as a clinical manifestation but also as a neurobiological mechanism underlying depressive disorder and other broader psychiatric conditions.
In children and adolescents, chronic low-grade inflammation has been implicated in the pathogenesis of co- and multi-morbid conditions to mental health disorders. Diet quality is a potential ...mechanism of action that can exacerbate or ameliorate low-grade inflammation; however, the exact way dietary intake can regulate the immune response in children and adolescents is still to be fully understood.
Studies that measured dietary intake (patterns of diet, indices, food groups, nutrients) and any inflammatory biomarkers in children and adolescents aged 2 to19 years and published until November 2020 were included in this systematic review, and were selected in line with PRISMA guidelines through the following databases: Academic Search Complete, CINAHL, Global Health, Medline COMPLETE and Web of Science-Core Collection. A total of 53 articles were identified.
Results show that adequate adherence to healthful dietary patterns such as the Mediterranean diet, or food groups such as vegetables and fruit, or macro/micro nutrients such as fibre or vitamin C and E, are associated with decreased levels of pro-inflammatory biomarkers, mainly c-reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), whereas adherence to a Western dietary pattern, as well as intake of food groups such as added sugars, macro-nutrients such as saturated fatty acids or ultra-processed foods, is associated with higher levels of the same pro-inflammatory biomarkers.
This is the first systematic review examining dietary intake and biological markers of inflammation in both children and adolescents. A good quality diet, high in vegetable and fruit intake, wholegrains, fibre and healthy fats ameliorates low-grade inflammation, and therefore represents a promising therapeutic approach, as well as an important element for disease prevention in both children and adolescents.
Glucocorticoids have been suggested to be involved in several neuropsychiatric disorders, including depression. One of the possible mechanisms through which glucocorticoids contribute to the ...development of the depressive symptomatology is via regulation of distinct neurogenic mechanisms in the brain. A preventive or protective approach for these patients might be the use of omega-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are known for they neuroprotective properties. We used the human hippocampal progenitor cell line HPC0A07/03C and pre-treated cells with either EPA or DHA, followed by treatment with the glucocorticoid cortisol either alone, or in co-treatment with the same n-3 PUFA during subsequent 3 days of proliferation and 7 days of differentiation. During proliferation, both EPA and DHA were able to prevent cortisol-induced reduction in proliferation and increase in apoptosis, when used in pre-treatment, and both pre- and co-treatment. During differentiation, EPA was able to prevent cortisol-induced reduction in neurogenesis and increase in apoptosis, when used in pre-treatment, and both pre- and co-treatment only during the proliferation stage; however, DHA required continuous treatment also during the differentiation stage to prevent cortisol-induced reduction in neurogenesis. Using transcriptomic analyses, we showed that both EPA and DHA regulated pathways involved in oxidative stress and immune response e.g., nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Signal transducer and activator of transcription 3 (STAT3), Interferon (IFN) and Interleukin (IL)-1 signaling, whereas DHA also regulated pathways involved in cell development and neuronal formation e.g., cAMP-response element binding protein (CREB) signaling. We provide the first evidence for treatment with both EPA and DHA to prevent cortisol-induced reduction in human hippocampal neurogenesis, and identify novel molecular mechanisms underlying these effects.
The reuse of food industry by-products constitutes one of the essential pillars of the change from a linear to a circular economic model. Drying is one of the most affordable techniques with which to ...stabilize by-products, making their subsequent processing possible. However, it can affect material properties. The objective of this study was to assess the effect of the drying temperature on the drying kinetics and final quality of the main artichoke processing by-products, bracts and stems, which have never been studied as independent materials. For this purpose, air drying experiments at different temperatures (40, 60, 80, 100 and 120 °C) were carried out. The alcohol insoluble residue (AIR) and the total phenolic content (TPC), antioxidant capacity (AC) and vitamin C (VC) of the fresh and dried samples were determined. The bracts dried faster than the stems, increasing drying rate with temperature. The two by-products presented relatively large amounts of AIR, the content being higher in bracts, but better functional properties in stems. The TPC, AC and VC values of the dried samples decreased in relation to the fresh samples, with the temperatures of 40 °C (bracts) and 120 °C (stems) being the most adequate for the purposes of preserving these characteristics.
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