SNRI effective treatment does not restore changes of immune and inflammatory parameters in depressed patients

Introduction: It has been hypothesized that major depression may be accompanied by alterations in cell-mediated and humoral immunity. Moreover, major depression appears to be associated with increased plasma concentrations of positive `acute-phase' proteins and increased production of cytokines. It has been suggested that an altered production of cytokines may underpin many changes of immune or inflammatory markers which have been observed. Our aim was to determine plasma concentrations of interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL6R), Tumor Necrosis Factor (TNF-\u3b1) and C reactive protein (CRP) in patients with major depression in an acute phase of illness and after 12 weeks of antidepressant treatment with SNRIs. Methods: 24 outpatients (M/F = 8/16; mean age 46.79\ub112.97) with a Major Depressive Disorder (MDD) during a Major Depressive Episode (MDE) and 20 healthy controls (M/F = 8/12, mean age = 40.05\ub111.02) have been recruited at the Institute of Psychiatry of the Catholic University in Rome. The severity of depression was assessed with the 21-item HDRS, anhedonia and retardation scores were evaluated by Snaith-Hamilton Pleasure Scale (SHAPS) and Depression Retardation Rating Scale (DRRS). Blood samples for the determination of C-reactive protein, TNF-alpha, IL-6 and sIL-6R were collected. Cytokines were measured using commercial enzyme linked immunosorbent assays (ELISA). Levels of C-reactive protein were measured using an immunoturbidimetric assay. Following baseline investigation all patients were treated with either venlafaxine (150\u2013225 mg) or duloxetine (60\u2013120 mg). Psychopathological status and laboratory testing were assessed before the admission and at the end of the study, after 12 weeks. Results: Plasma concentrations of IL-6 (0.59\ub11.14 vs. 0.06\ub10.27 pg/ml) and CRP (3.28\ub13.59 vs. 1.33\ub11.48 mg/ml) were significantly higher in depressed patients than in healthy controls. sIL-6R and the product of IL-6 and sIL6R were higher but not significantly. There was no difference in plasma concentrations of TNF-\u3b1 between depressed patients and healthy controls. A significant positive correlation between CRP and IL-6 (r = 0.25, p = 0.047) has been observed. All patients significantly improved after treatment and most of them (62.5%) achieved a full remission. Finally, antidepressant treatment with SNRIs did not significantly change plasma IL-6, sIL-6R, TNF-\u3b1, CRP. Conclusions: Changes of plasmatic levels of IL-6 and CRP in depressed patients are consistent with previous findings. Despite the clinical efficacy SNRIs did not appear to have a significant effect on immune parameters in major depression. Our finding is in contrast with O'Brien et coll. that observed a significant drop of C-reactive protein after SSRIs and showed an anti-inflammatory response independent of antidepressive action. The immune alteration in major depression seems to be trait rather than state associated and the inflammation response could not be directly involved in the pathophysiology of depression. The efficacy of antidepressant treatment may reflect indirect immunomodulatory effects rather than a direct down-regulation of inflammatory response activation. Further researches in larger samples are needed to clarify the involvement of immune variables in major depression and the influence of SNRIs

Epstein-Barr virus antibodies in serum and cerebrospinal fluid from Multiple Sclerosis, Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Amyotrophic Lateral

Elevated anti-Epstein-Barr virus (EBV) antibody levels are present in serum of Multiple sclerosis (MS) patients but literature lacks of studies comparing anti-EBV antibody levels between MS and other neurological diseases. We evaluate anti-VCA IgG and IgM, anti-EBNA1 IgG, anti-Cytomegalovirus IgG and IgM titres in serum and cerebrospinal fluid (CSF) of 267 MS, 50 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and 88 Amyotrophic Lateral Sclerosis (ALS) patients. We found increased titres of anti-EBV-IgG in serum and CSF of MS subjects as compared to CIDP and ALS patients thus providing additional evidence for a possible involvement of EBV in MS

Role of spiramycin/cotrimoxazole association in the mother-to-child transmission of toxoplasmosis infection in pregnancy.

The purpose of this report is to evaluate the efficacy and safety of spiramycin/cotrimoxazole in the mother-to-child transmission of Toxoplasma gondii infection. We retrospectively analysed 76 infants born to mothers with toxoplasmosis during pregnancy and estimated the risk of mother-to-child transmission considering the gestational age at the time of infection. Seventy-six mothers were given spiramycin, cotrimoxazole and folinic acid; only two babies (2.6%) were infected by Toxoplasma and none of them showed signs or symptoms of congenital infection or interference of sulphamid on tetrahydrofolate reductase (THFR) either at birth or during follow-up. Treatment did not need to be stopped in any mother because of adverse drug effects. Our results seem to encourage the use of spiramycin/cotrimoxazole in women with toxoplasmosis during pregnanc

Alterazioni delle risposte immuno-infiammatorie nei pazienti affetti da disturbo depressivo maggiore (Immune-inflammatory response changes in patients with major depressive disorder)

Objectives It has been hypothesized that major depression is accompanied by alterations in cell-mediated and innate immunity. Moreover, major depression appears to be associated with increased plasma concentrations of positive ‘acute-phase’ proteins and increased production of cytokines. It has been suggested that an altered production of cytokines may underlie numerous recognized changes of immune or inflammatory markers. The aim of our study was to evaluate the usefulness of high-sensitivity C-reactive protein (hs-CRP) values in identifying a state of immune-inflammatory activation in patients with major depressive disorder. In particular, in order to assess the reliability of this inflammatory parameter in depression, we measured changes in hs-CRP values as well as its correlation with both the levels of some cytokines [interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL6R) and Tumor Necrosis Factor (TNF-α)] and the clinical characteristics of the sample (severity of symptoms, specific psychopathological dimensions, etc.). Methods 24 outpatients (M/F = 8/16; mean age 46.79 ± 12.97) with a Major Depressive Disorder (MDD) during a Major Depressive Episode (MDE) and 20 healthy controls (M/F = 8/12, mean age = 40.05 ± 11.02) were recruited at the Institute of Psychiatry of the Catholic University in Rome. Depression severity was as- sessed with 21-item HDRS, while anhedonia and psychomotor retardation were evaluated with Snaith-Hamilton Pleasure Scale (SHAPS) and Depression Retardation Rating Scale (DRRS). Blood samples for the determination of hs-CRP, TNF-α, IL-6 and sIL-6R were collected. Cytokines were measured using commercial enzyme linked immunosorbent assays (ELISA). Levels of hs- CRP were measured using nephelometric assay. Results The patients included in the study mostly had moderate depressive symptoms at baseline (Table I). Plasma concentrations of IL-6 (0.59 ± 1.14 vs. 0.06 ± 0.27 pg/ ml) and hs-CRP (3.28 ± 3.59 vs. 1.33 ± 1.48 mg/ml) were significantly higher in depressed patients compared to healthy controls. sIL-6R levels along with receptor-ligand binding activity (product IL-6 × sIL6R) were higher in depressed patients compared to healthy controls, though not significantly. There were no differences in plasma concentrations of TNF-α between de- pressive patients and healthy controls (Table II). A significant positive correlation between hs-CRP and IL-6 (r = 0.25, p = 0.047) was found. The analysis of a possible correlation between different inflammatory markers (hs-CRP, IL-6, sIL-6R and TNF-α) and scores on psychometric scales (HDRS, BPRS, DRRS and SHAPS) showed no statistical significance. Immune system and acute phase response activation, therefore, shows no correlation with severity of depressive symptoms and psychopathological profile (anhedonia and psychomotor retardation). Conclusions Although plasma cytokine assays are highly specific and sensitive measurs in defining immune profile, they are quite expensive. The use of hs-CRP in our study has, on the contrary, proven to be sufficiently reliable and potentially applicable to routine clinical practice, so to identify those subjects with the highest levels of immune dysregulation. Further studies on larger samples, more adequately characterized with respect to clinical course and characteristics, are necessary to increase our understanding of the role played by immune activation in major depression

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys