Psychoneuroimmunology and health psychology: inflammation and protective factors.

A common clinical observation is the adverse relationship between stress and human diseases. The attention of scientific research on health has been disproportionately focused on risk factors that predict the onset of certain health outcomes, in particular there has been an increasing interest in the role of inflammation as a common mechanism of disease in a number of medical and neuropsychiatric diseases. Despite the importance of such research being undisputed, it is necessary to emphasize what the protective factors are that promote psychosocial recovery processes and increased survival rates in a biopsychosocial perspective. This article aims to understand the relationship between psychosocial factors and immune system in the interests of health psychology, highlighting the protective factors that promote recovery, resiliency and resistance to disease.

Is there a role for agomelatine in the treatment of anxiety disorders?A review of published data.

Anxiety disorders (Ads) are the most common type of psychiatric disorders, Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic antidepressants (NaSSA) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Agomelatine, a new melatonergic antidepressant, has been shown effective in various types of mood disorders. Moreover, some evidence points towards a possible efficacy of such a drug in the treatment of ADs. Therefore, the aim of this review was to elucidate current (facts and views) data on the role of agomelatine in the treatment of ADs. The trials evaluating agomelatine in the treatment of generalized anxiety disorder are few but, overall, encouraging in regards to its efficacy. However, further randomized, placebo-controlled studies on larger samples use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature regarding agomelatine in the treatment of other ADs, such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of agomelatine in generalized anxiety (GAD) warrants further investigation in ADs.

The role of oxytocin in plasticity, memory and attachment dynamics.

The peptide hormones oxytocin (OT) and arginine vasopressin (AVP) have been implicated in the regulation of mammalian social behavior. There is considerable evidence implicating both oxytocin and vasopressin in social recognition and social memory. This review explores their role in attachment dynamics. Oxytocin is one element in a complex network of interactions observed in natural phenomena ranging from molecular biology, etology, social behavior and human psychology.

Relationship between cancer and psychology: an updated history.

The mechanism and formation of cancer have always been topics of interest for scientists, even for doctors in ancient times. Nowadays a great role for cancer is played by psychological stress which promotes relevant changes in neuronal activity and gene regulations across the different brain areas. It has been reported by many authors that stress can have an important role in the immune system and may be relevant in the formation of cancer. Our observations, in accordance with other research studies, confirm the importance of the influence of depression, linked to neuroendocrine stress, on the enhancement of cancer pathogenesis by inhibiting anti-tumor immune responses. In this article we review the past and present history of the relationship between cancer and psychology.

Psychological stress and vitamins.

Conditions of stress and anxiety have complex interactions with insufficient vitamin intake and malnutrition. This study, based on literature research in Medline, analyzes the inter-relationship between vitamins and stress. This report concerns a number of vitamins that have been receiving much attention in earlier reviews of the literature, for their potential to protect against stress-related events, and focus is placed upon recent findings.

Psychological stress and cancer.

All the concepts reported in this editorial are based on recent literature data obtained through a PubMed search, using both Medline and manual searches, with particular reference to articles, which could be relevant to clinical practice. This paper contributes to the existing literature on depression and stress and provides important information for the development of effective strategies to manage these conditions among patients with cancer.

Major depressive disorder, anhedonia and agomelatine: an open-label study.

Despite a wide range of available antidepressants, the effect of the treatment is often suboptimal and there is a need for more effective and better tolerated drugs. Unlike other antidepressants, agomelatine represents a new approach to depression with an innovative mechanism of action. It is an agonist of melatoninergic receptors MT1 and MT2 and a selective antagonist of 5-HT2c receptors. In this open-label 8-week study we aimed to investigate the efficacy of agomelatine on depressive symptoms in patients with major depression. Secondary endpoints were the effect of agomelatine on anhedonia. Thirty major depressive patients received a flexible dose (25-50 mg; per os, daily) of agomelatine. Depressive (Hamilton Depression Scale) and anxious (Hamilton Anxiety Scale) symptoms, anhedonia (Snaith Hamilton Rating Scale), and sleep quality (Leeds Sleep Evaluation Questionnaire) were assessed. Twenty-four patients (80%) completed 8 weeks of treatment. Significant improvements were seen at all visits on the HAM-D (p<.05), HAM-A(p<.01), SHAPS (p<.05), LSEQ (p<.05). Nine subjects (30%) were responders and 5 (17%) remitters at week 1; 18 (60%) were remitters by the end of the trial. There was no serious adverse event. No aminotrasferase elevations were noted. In line with previous studies, in which agomelatine was associated with early clinical improvement, this study also provides evidence of an early response and the findings of improvements in depression scores. Moreover, this is the first study where agomelatine was effective in the treatment of anhedonia. Additional trials are needed to delineate the place of agomelatine in the contemporary pharmacotherapy for depressive disorders.

Interlationship between psychology and cytokines.

Leukocytes and other types of cells produce proteins or glycoproteins, termed cytokines, that serve as chemical communicators from one cell to another. Neuromediators are able to modulate functions of immune cells and other cells and the relationship between the central nervous system (CNS) and the endocrine system have been known for many years. Communication between nerves and immune and inflammatory cells plays a major role in the modulation of several dysfunctions including ion transport, mucosal permeability and cytokine production. Cytokines are involved in both injury and repair, and the conditions underlying these distinct outcomes are under intense investigation and debate. Evidence from medical studies implicates the immune system in a number of psychiatric disorders with known or suspected developmental origins, including schizophrenia, anxiety-depression, and cognitive dysfunction.

The effect of newer serotonin-noradrenalin antidepressants on cytokine production: a review of the current literature.

Cytokines may influence brain activities especially during stressful conditions, and elevated levels of IL-6 and C-reactive protein have been pointed out in subjects with Major Depression. If pro-inflammatory cytokines play a causative role in major depressive disorders, one would expect that antidepressants may down-regulate these cytokines or interfere with their actions, leading to improvement of depressive symptoms. Accumulating evidence has been published that antidepressants modulate cytokine production and this is particularly true for Tricyclics and Selective serotonin reuptake inhibitors (SSRIs), but the influence of newer antidepressants acting on both serotonin (5-HT) and norepinephrine (NE) such as venlafaxine, duloxetine and mirtazapine on cytokine levels has not been extensively studied. However, both pre-clinical and clinical studies examined in this review have demonstrated that newer serotonin-noradrenalin antidepressants can inhibit the production and/or release of pro-inflammatory cytokines and stimulate the production of anti-inflammatory cytokines, suggesting that reductions in inflammation might contribute to treatment response. Moreover, the results of the present review support the notion that the serotonin-noradrenalin antidepressants venlafaxine and mirtazapine may influence cytokine secretion in patients affected by MD, restoring the equilibrium between their physiological and pathological levels and leading to recovery. To date, no studies have evaluated the effect of duloxetine, the newest serotonin-noradrenalin antidepressant, on cytokine levels and therefore this should be evaluated in future studies.

The role of cholesterol levels in mood disorders and suicide.

The individuation of sensitive and specific biochemical markers, easily assessable on large samples of subjects and usefully employable as predictors of severe psychiatric disorders, such as mood disorders, could help clinicians to improve the diagnostic and therapeutic processes facilitating the long-term follow-up. In particular, serum cholesterol levels may potentially be optimal markers due to their relative easy sampling and low cost. The involvement of cholesterol in affective disorders such as Major Depression (MD), Seasonal Affective Disorder (SAD) and Bipolar Disorders (BD) is a debated issue in current research. However, current literature is controversial and, to date, it is still not possible to reach an agreement on its possible usefulness of cholesterol as a biological marker of affective disorders. Despite the controversial results on the relationships between cholesterol levels and affective disorders, the majority of literature seems to show a more consistent relationship between cholesterol levels and suicidal behaviour, with few studies that have found no relationships. The aim of this review is to elucidate current facts and views about the role of cholesterol levels in mood disorders as well as its involvement in suicidal behaviour.

Autism and immunity: revisited study.

Autism spectrum disorder is of interest neurochemically because it represents a relatively homogeneous disorder with regard to disease development, abnormal cognitive development and intellectual development disturbance. A consistent finding in autistic children is a high number of mast cells and a high level of serotonin which is also found at elevated concentrations in the urine of autistic patients. In addition, a dysfunction of clinical conditions, such as gastrointestinal and immunological symptoms, is frequently noted in autistic children, however, IgE does not appear to be prevalent in these children but probably an increase of cytokines/chemokines produced by mast cells at an early age may play an important role. Therefore an immune hypothesis, involving also autoimmunity, is one possible pathogenetic mechanism in autism. In conclusion, mast cell activation could contribute to immune and neuroinflammatory abnormalities that are evident in patients with autism spectrum disorders.

Neuropeptide substance P induces mRNA expression and secretion of CXCL8 chemokine, and HDC in human umbilical cord blood mast cells.

PURPOSE: Mast cells play an important role in innate and acquired immunity and are thought to be the cellular origin of most proteases and cytokines. Substance P (SP) and its receptor, NK-1R, play critical roles in immune regulation in human and animal models of inflammation. METHODS: We used mature human cord blood mast cells (HCBMC) differentiated from cord blood CD34+ precursor activated with SP in culture. RESULTS: Our data indicate that Substance P strongly activates mature HCBMC in releasing CXCL8 expression and secretion ( CONTROL: 1.200 +/- 1.0; SP: 4.10 +/- 0.90; P < 0.01). Moreover, in a RT-PCR, HCBMC expressed CXCL8 mRNA after Substance P activation. Since calcium ionophore A23187 is a pharmacological activator that raises cytosolic free calcium ion concentraion and stimulates mast cells in the production and secretion of proinflammatory compounds, it was used as positive control. In addition, we found that HCBMCs generate the transcription of histidine decarboxylase (HDC), the enzyme responsible for the generation of histamine from histidine, after SP treatment. Since CXCL8 is a member of the CXC chemokine subfamily with potent chemotactic activity and is a primary inflammatory cytokine we conclude that our results, obtained from HCBMC cultures, a good and valid model in vitro, support the concept that the neurogenic system modulates inflammatory events by Substance P-mediated HCBMC chemokine CXCL8 release. CONCLUSION: The expression, synthesis and release of CXCL8 suggest an increase of inflammatory process in vivo mediated by the recruitment and infiltration of inflammatory cells in inflamed tissues.

Evaluation of plasma antioxidant levels during different phases of illness in adult patients with bipolar disorder.

The aim of the present study is to evaluate role of plasma antioxidants (albumin, bilirubin and uric acid) in patients suffering from type I Bipolar Disorder (BD-I) during different phases of illness: acute mania, euthymia and bipolar depression. Medical records of consecutive 110 BD-I patients (38 patients with acute mania, 35 in euthymic state, full remission, and 37 in depressive phase) were reviewed to evaluate plasma antioxidant levels. Laboratory data of 40 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. Serum uric acid levels were higher in acute mania than other patient subgroups and healthy controls. Serum uric acid levels directly correlated with BRMRS and YMRS scores. No differences were found between clinical groups during different phases and healthy controls concerning albumin and bilirubin. In conclusion, the results of the present study support the notion that serum uric acid levels may be higher in patients with BP-I (especially during manic phases) which may suggest a dysregulation of the purinergic system. However, limitations should be considered and further studies are needed.

Biology of neurotensin: revisited study.

The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary neurotransmitter or neuromodulator of classical neurotransmitters. Morphological and functional in vitro and in vivo studies have demonstrated the existence of close interactions between NT and dopamine both in limbic and in striatal brain regions. Additionally, biochemical and neurochemical evidence indicates that in these brain regions NT also plays a crucial role in the regulation of the aminoacidergic signalling. Immune cells, such as lymphocytes, macrophages and mast cells are reported to be activated by neuropeptides, such as neurotensin; this activation leads to cytokine and immunoglobulin production. In addition, neurotensin increases calcium level and the production of nitric oxide. Therefore neurotensin is deeply involved in immunity and inflammation but its real function still remains to be elucidated.

Evaluation of C-reactive protein and total serum cholesterol in adult patients with bipolar disorder.

The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.

Severe tramadol addiction in a 61 year-old woman without a history of substance abuse.

We describe here the first case of Tramadol addiction and withdrawal in an elderly female patient in apparently good physical health. We report successful treatment with mirtazapine and clonidine. We believe that patients must be advised to take Tramadol regularly and to stop gradually especially after long treatment periods; moreover physicians must consider the potential physical dependence when they prescribe Tramadol for pain. Hence, we are observing some patients who continue to take Tramadol in order to achieve a feeling of well-being, even though their pain is controlled after disease regression. Finally, the establishing of an evidence-based Tramadol detoxification protocol would be highly desirable.

Quality of life in non-allergic rhinitis depends on the predominant inflammatory cell type.

Three main types of inflammatory Non-Allergic Rhinitis (NAR) have been defined: NAR infiltrated by eosinophils (NARES), by mast cells (NARMA), and by neutrophils (NARNE). In the absence of studies that investigated the Quality of Life (QoL) in NAR, the present work is aimed at evaluating the Quality of Life of patients with NARES, NARMA, and NARNE. One hundred thirty one (131) NAR patients were prospectively and consecutively evaluated: 54 patients with NARES, 38 with NARMA, and 39 with NARNE. Their history, nasal infiltration and rhinomanometry were characterized, and Quality of Life (using 2 instruments) was evaluated, and associated to clinical and histological features. Quality of Life was significantly different in the 3 groups (p less than 0.001); NARES patients had the worst Quality of Life. Nasal resistances were significantly higher in the NARES group. Significant associations were shown in NARES patients between Quality of Life and nasal function. This study provides the first evidence that Quality of Life is impaired in NAR as well as in allergic rhinitis. Furthermore, Quality of Life impairment differs among the various forms of NAR, and there is a correlation with the cellular infiltrating type.

Subjective and psychopathological response in patients under different antipsychotic treatments: are there differences in real clinical practice?

The aim of this study is to investigate whether subjective well-being in patients under treatment with typical (ATPs) and atypical antipsychotic (ATPsA) compounds can be compared with the improvement of psychopathological state and to verify if both variables correlate to adherence to treatment. We assessed 106 consecutive patients receiving ATPs or ATPsA in the University Psychiatric Ward of L?Aquila, according to DSM-IV diagnosis of Schizophrenia and Bipolar Disorder. Psychopathological state was assessed by Brief Psychiatric Rating Scale-4.0 version (BPRS), adherence to treatment and subjective well-being was assessed by Drug Attitude Inventory (DAI-10) and Subjective Well-being under Neuroleptics (SWN), respectively. BPRS and DAI-10 were administered on admission (T0) and at the end of recovery (T1). The subjects enrolled in this study were divided into 2 groups according to ATP prescribed. We observed an improvement of BPRS and SWN total scores in each group, and increasing scores in DAI-10, from admission to discharge, both in total samples and in each group. There were statistical differences between the patients receiving ATPs and those receving ATPsA regardindg the SWN total score and its different dimensions. This study emphasizes that patients receiving ATPsA show better subjective response compared with patients undergoing ATP treatment, although the adherence to pharmacotherapy and clinical improvement do not differ between the groups.

The role of C-reactive protein in mood disorders.

Recently, a possible relationship between C-Reactive Protein (CRP), a marker of underlying low-grade inflammation, and mood disorders has been proposed by some researchers. The aim of this review is to elucidate the current facts and views about CRP in mood disorders such as Depressive and Bipolar Disorders. Several studies have examined the relationship between affective disorders and CRP, but the majority of the studies in literature have been limited by retrospective, case-controlled study design, and very few studies have examined the relationship between depression and CRP in large study samples. In conclusion, the role of CRP in mood disorders is, to date, intriguing but somewhat unclear. Further prospective studies are needed to introduce the CRP in clinical settings as a marker of affective states and suicidability.

Rat basophilic leukemia cells (RBL-2H3) generate prostaglandin D2 (PGD2) after regulated upon activation, normal T-cell expressed and secreted (RANTES) activation.

Increasing evidence indicates that local neurogenic inflammation, possibly in response to different stimuli, may be involved in sensory nerve sensitization, migraine generation and some other precipitating events leading to neuronal dysfunction in the brain. In addition, mast cells generate eicosanoids that are linked to asthma and other inflammatory diseases. Regulated upon activation, normal T-cell expressed and secreted (RANTES) is a small protein and a prototype member of the CC chemokine-beta subfamily with chemoattractant and inflammatory properties. In this study we used the RBL-2H3 cell line to determine whether or not these cells generate prostaglandin D2 (PGD2) after treatment with RANTES. After 4 hours of incubation, RBL-2H3 cells cultured with RANTES at 20 ng/mL released large amounts of PGD2 in a dose-response manner compared to control. Moreover, RBL-treated RANTES generated a large quantity of histamine. Our study confirms once again the proinflammatory action of RANTES, in this case acting on the stimulation of the arachidonic acid cascade product PGD2.