Impact of mast cells in depression disorder: inhibitory effect of IL-37 (new frontiers).

The purpose of this article is to study the involvement of inflammatory mast cells (MCs) in depression which may be inhibited by IL-37. We evaluate mast cells in depression on the basis of our previous experimental data, and using the most relevant studies reported in the literature. Dysfunction of mood, feelings, and thoughts is a major risk factor for several metabolic diseases and may influence the physiology of the body leading to depression. Depression, present in mastocytosis, is an important endogenous process that promotes the activation of meningeal cell receptors through a low-grade neurogenic chronic inflammation, and MCs. Mast cells are localized along meningeal blood vessels and connective tissues, as well as between the ganglion cells and nerve fibers. They are present in the hypothalamus of mammalian brains capable of communication with nerves. MCs are classically activated by binding to IgE cross-link FcεRI high-affinity receptor leading to release a plethora of mediators responsible for the generation of inflammatory cytokines. Corticotropin-releasing hormone (CRH), produced by MCs, has been found in microglial cells where it regulates immune cells and contributes to the pathogenesis of neurodegenerative diseases including depression. Inflammatory cytokines released by MCs aggravate depression and could be partially inhibited by IL-37. A detailed understanding of the interaction between the immune system, including MCs and depression, is necessary in order to address an effective therapy which could include IL-37. As a consequence, the concepts reviewed here have treatment implications.

Quality of life, depression, and cytokine patterns in patients with chronic hepatitis C treated with antiviral therapy.

PURPOSE: To evaluate the effect of chronic hepatitis C and antiviral therapy on health-related quality of life (HRQoL), depression symptoms and cytokine patterns. METHODS: Twenty HCV+ patients treated with peginterferon plus ribavirin were enrolled in this cohort study and invited to complete SF-12 and BDI questionnaires prior to (T0) and at the end of the treatment (T1). HCV-RNA, serum levels of ALT, AST, haemoglobin, ferritin and IFN-gamma, TNF-alpha, IL-2, IL-4, IL-6 and IL-10 were evaluated at T0 and T1. The questionnaire results were correlated to biochemical and cytokine parameters. RESULTS: Two patients (1%) dropped out and 18 HCV patients composed the final sample (11 males (61.1%); mean age 42.5+/-11.9 yr; mean disease duration 9.7+/-6.9 yr). Between T0 and T1 ALT (p=0.02), AST (p=0.052) HCV-RNA (P=0.0002) and haemoglobin levels decreased (p=0.0003), whereas ferritin level increased (P=0.003). Also, at T1 all cytokine levels were augmented. Regarding depression status, at T0 10 patients (55.5%) scored above to the BDI questionnaire (suggesting clinically significant depression), whereas at T1 14 patients scored 10 or above (77.7%). At T1 the mean BDI score increased, but this difference was not significant. Regarding HRQoL, the majority of patients had T0 summary scores < or = 50. At T1 HRQoL changed and scores decreased in 66.7% of the patients. A correlation was observed between the T0 level of ferritin and the amount of change in BDI and SF-12 mental score between T0 and T1 (Spearman rho = -0.56 and +0.61, respectively) and IL-4 level at T0 and the change in BDI and SF-12 mental scores (Spearman rho = -0.49 and +0.45, respectively). CONCLUSION: BDI, SF-12, IL-4 and ferritin are good tools to predict the appearance of depressive symptoms and worsening of the quality of life in the HCV+ population.

Alexithymia and its relationships with dissociative experiences and Internet addiction in a nonclinical sample.

The aim of the present study was to evaluate alexithymia, dissociative experiences, and Internet addiction (IA) in a nonclinical sample of 312 undergraduate students, identifying predictive factors associated with the possible risk of developing IA. We found that alexithymics had more consistent dissociative experiences, lower self-esteem, and higher obsessive-compulsive symptoms than nonalexithymics. In addition, alexithymics reported a higher potential risk for IA when compared to nonalexithymics. Difficulty in identifying feelings, higher dissociative experiences, lower self-esteem, and higher impulse dysregulation were associated with higher IA. Thus, a combination of alexithymia, dissociative experiences, low self-esteem, and impulse dysregulation may be a risk factor for IA, at least in a nonclinical sample.

Epileptic EEG discharges and short non-convulsive crisis: Influence on cognitive and psychobehavioural functions in youths.

PURPOSE: Learning and behavioural difficulties often occur in benign childhood epilepsy. In recent years, several electroencephalogram (EEG) characteristics have been related to the occurrence of learning and behavioral problems. We determined if the cognitive characteristics of epileptic children depend exclusively on illness factors, or if epileptic electroencephalogram discharges during the crisis contribute to these changes. METHODS: We studied a randomly selected group of 150 youths with short non-convulsive crises, who completed cognitive testing and electroencephalographic studies. The inclusion criteria were: undefined crisis, variations in cognitive function and/or frequent epileptiform discharges on the electroencephalogram. RESULTS: Previous research indicates that the type of epilepsy and the patient's educational level can influence cognitive functioning. The electroencephalographic epileptic discharges during the crisis has been found to influence cognitive transitory functions such as vigilance or swiftness of mental functions. The type of epilepsy is correlated statistically with impairment of learning ability tests: reading (F, 5.487, P = 0.005) and mathematics (F, 3.007, P < or = 0.05). In addition, 40% of the epileptic patients had behavioural disordered versus 16% for the control group (P < 0.02). CONCLUSIONS: Our results show dissociation between the characteristic directly dependent on epilepsy, particularly the type of epilepsy, on stable cognitive functions, such as the progress in school, and the effect of parosystic anomalies or the immediate effect of crisis and EEG dischargeson cognitive processes.

Expression and secretion of CXCL8 (IL-8), release of tryptase and transcription of histidine decarboxylase mRNA by anti-IgE-activated human umbilical cord blood-derived cultured mast cells.

Activation of cytokine receptors and alterations in cytokines are thought to play important roles in neuronal dysfunction and in the pathogenesis of the nervous system diseases. CXCL8 (IL-8) is a CXC chemokine with chemotactic and inflammatory properties. Chemokines control mast cell infiltration in several inflammatory diseases, including stress and neurological dysfunctions. Using isolated human umbilical cord blood-derived cultured mast cells (HUCMC) from hematopoietic stem cells CD34+, mast cells were immunologically activated with anti-IgE at concentrations of 1, 5, 10 and 20 microg/ml leading to the dose-dependent production of IL-8 (p < 0.05). The increase in IL-8 mRNA expression was also noted when the cells were treated with anti-IgE at 10 microg/ml for 6 h. Immunologically activated HUCMC provoked the generation of tryptase in a dose- and time-dependent manner. We also found increased histidine decarboxylase (HDC) expression in activated HUCMC after 6 h of incubation, a rate-limiting enzyme responsible for the generation of histamine from histidine. Taken together, these results confirm that anti-IgE-activated mast cells release inflammatory mediators including CXCL8, a CXC chemokine which regulates several biological effects of mast cells, e.g. chemoattraction, and possibly causes cell arrest.

Antidepressant therapy can improve adherence to antiretroviral regimens among HIV-infected and depressed patients.

Several strategies have been introduced to manage nonadherence to highly active antiretroviral therapy (HAART). Treatment with antidepressants may improve self-reported adherence. In this brief report, a small sample of HIV-depressed patients (n = 9) were treated for a 6-month period with antidepressants improving self-reported adherence based on the HAART scale (poor, good, satisfactory, and optimal). Before the antidepressant treatment, adherence was reported as "good" by 3 patients and "satisfactory" by 6 patients. After antidepressant therapy, adherence to antiretroviral regimes was statistically higher in HIV-depressed on treatment than in HIV-depressed patients not treated with antidepressants (P < 0.0001). We used chi2 test with a significance level at P < 0.05. Treating depression in HIV-infected patients may serve to improve adherence to HAART.

The G51S purine nucleoside phosphorylase polymorphism is associated with cognitive decline in Alzheimer's disease patients.

Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose etiopathology is still unclear, however several genetic factors have shown to increase the risk of developing the disease. Purine nucleotides and nucleosides play an important role in the brain. Besides their role in neurotransmission and neuromodulation, they are involved in trophic factor release, apoptosis, and inflammatory responses. These mediators may also have a pivotal role in the control of neurodegenerative processes associated with AD. In this report the distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution serine to glycine at position 51 (G51S), was investigated in a large population of AD patients (n=321) and non-demented control (n=208). The PNP polymorphism distribution was not different between patients and controls. The polymorphism distribution was also analyzed in AD patients stratified according to differential progressive rate of cognitive decline during a 2-year follow-up. An increased representation of the PNP AA genotype was observed in AD patients with fast cognitive deterioration in comparison with that from patients with slow deterioration rate. Our findings suggest that the G51S PNP polymorphism is associated with a faster rate of cognitive decline in AD patients, highlighting the important role of purine metabolism in the progression of this neurodegenerative disorder.

Neurologic soft signs in schizophrenic patients treated with conventional and atypical antipsychotics.

Neurologic soft signs (NSS) are considered a somatic feature associated with schizophrenia (DSM-IV) that are present in neuroleptic-treated, as well as untreated or first-episode patients. The aim of this study was to determine the incidence and severity of NSS in groups of schizophrenic patients treated with either a conventional neuroleptic medication, haloperidol (n = 37), or atypical antipsychotic medications, risperidone (n = 19), clozapine (n = 34), and olanzapine (n = 18). NSS were assessed with the Neurological Evaluation Scale (NES), whereas extrapyramidal symptoms (EPS), which occur more commonly with conventional neuroleptic treatment, were evaluated using the Simpson-Angus Scale. NES scores were not significantly different between groups. Slight differences were found for 2 items only. The haloperidol group showed higher scores for the "Romberg test," whereas the clozapine group showed higher scores for "short-term memory." There were significant correlations between EPS and NES total score in the haloperidol and risperidone groups. These results demonstrate an overall overlapping of NSS among the groups, confirming their substantial independence from neurologic implications of neuroleptic treatment.