One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial.

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Cross-cultural and socio-demographic correlates of homophobic attitude among university students in three European countries.

PURPOSE: The aim of this study was to investigate homophobic attitudes in three European countries: Italy, Albania, and Ukraine. One thousand and forty-eight students were recruited in Italian (n = 766), Albanian (n = 180), and Ukrainian (n = 102) university centers. METHODS: A socio-demographic questionnaire and Homophobia Scale (HS) were administered by our staff. RESULTS: Cross-cultural and significant differences among Italian, Albanian, and Ukrainian students were found on the Homophobia Scale (HS; Italy: mean = 22.26 ± 16.73; Albania: mean = 38.15 ± 17.28; Ukraine: mean = 59.18 ± 16.23). The analysis of socio-demographic characteristics revealed that the male gender emerged as main predictor of homophobic attitude in all the three countries, although also a conservative political orientation and the religious belief predict higher homophobia levels in Italy and Albania, particularly. CONCLUSIONS: This study revealed that in these European countries assessed, attitudes toward homosexuality are different. Ukrainians display higher levels of homophobia than Albanians and Italians, confirming the central role of cultural differences in homophobic attitudes. Nevertheless, some socio-demographic aspects such as identification as male have a similar influence on homophobic attitudes in all assessed populations.

Common variant at 16p11.2 conferring risk of psychosis.

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association study, meta-analysis and follow-up (totaling as many as 18 206 cases and 42 536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7469 bipolar disorder cases, 1535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46 160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T]; odds ratio=1.08; P=6.6 × 10(-11)). The new variant is located within a 593-kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P=0.0039 in the public GIANT consortium data set; P=0.00047 in 22 651 additional Icelanders).

Migraine improvement during short lasting ketogenesis: a proof-of-concept study.

BACKGROUND AND PURPOSE: Ketogenesis is a physiological phenomenon due to starvation or a ketogenic diet (KD), a drastic restricted carbohydrate dietary regimen that induces lipid metabolism and ketone body synthesis. Two patients whose migraines disappeared only during, and not outside, cycles of very-low-calorie KD performed to reduce their weight were recently observed. To confirm our observation, in a dietitian clinical setting two parallel groups of migraineurs, one receiving a 1-month very-low-calorie KD prescription followed by a 5-month standard low-calorie diet (SD) and the other a 6-month SD, were followed. METHODS: Ninety-six overweight female migraineurs were enrolled in a diet clinic and blindly received a KD (n = 45) or an SD (n = 51) prescription. Mean monthly attack frequency, number of days with headaches and tablet intake were assessed before and 1, 2, 3 and 6 months after diet initiation. RESULTS: In the KD group, the baseline attack frequency (2.9 attacks per month), number of days with headaches (5.11 days per month) and tablet intake (4.91 doses per month) were significantly reduced after the first month of diet (respectively 0.71, 0.91, 0.51; overall, KD versus baseline, P < 0.0001). During the transition period (first versus second month), the KD group showed a transient worsening of each clinical headache variable (respectively 2.60, 3.60, 3.07), despite being improved compared with baseline, with continuous improvement up to month 6 (respectively 2.16, 2.78, 3.71). In the SD group, significant decreases in the number of days with headaches and tablet intake were observed only from month 3 (P < 0.0001), and in attack frequency at month 6 (P < 0.0001). CONCLUSIONS: The underlying mechanisms of KD efficacy could be related to its ability to enhance mitochondrial energy metabolism and counteract neural inflammation.

A critical review and meta-analysis of the perceptual pseudoneglect across psychiatric disorders: is there a continuum?

The phenomenon known as "perceptual pseudoneglect" refers to the leftward bias in visuospatial attention in non-clinical samples, possibly as a consequence of right hemisphere dominance for visuospatial attention. The degree of such a lateralized visuospatial attention bias is often assessed using the line bisection task. Interestingly, various psychiatric disorders may influence the expression of this phenomenon. The aim of this paper was to perform a critical appraisal of the literature on the expression of the perceptual pseudoneglect across all psychiatric disorders accompanied by meta-analytical evaluation of the data. Moreover, we will discuss whether this phenomenon may be considered as a trait marker across different psychiatric disorders.

Favourable prognostic value of antibodies anti-HSP20 in patients with cystic echinococcosis: a differential immunoproteomic approach.

Seeking biomarkers reflecting disease development in cystic echinococcosis (CE), we used a proteomic approach linked to immunological characterisation for the identification of respective antigens. Two-dimensional gel electrophoresis (2-DE) of sheep hydatid fluid, followed by immunoblot analysis (IB) with sera from patients with distinct phases of disease, enabled us to identify by mass spectrometry heat shock protein 20 (HSP20) as a potential marker of active CE. Using IB, antibodies specific to the 34 kDa band of HSP20 were detected in sera from 61/95 (64%) patients with CE, but not in sera from healthy subjects. IB revealed anti-HSP20 antibodies in a higher percentage of sera from patients with active disease than in sera from patients with inactive disease (81 vs. 24%; P = 10(-4)). These primary results were confirmed in a long-term follow-up study after pharmacological and surgical treatment. Herewith anti-HSP20 antibody levels significantly decreased over the course of treatment in sera from patients with cured disease, relative to sera from patients with progressive disease (P = 0·017). Thus, during CE, a comprehensive strategy of proteomic identification combined with immunological validation represents a promising approach for the identification of biomarkers useful for the prognostic assessment of treatment of CE patients.

Allelic frequencies of 3' Ig heavy chain locus enhancer HS1,2-A associated with Ig levels in patients with schizophrenia.

Infectious and autoimmune pathogenic hypotheses of schizophrenia have been proposed, prompting searches for antibodies against viruses or brain structures, and for altered levels of immunoglobulins. Previous experiments have shown that allele frequencies of the Ig heavy chain 3' enhancer HS1,2*A are associated with several autoimmune diseases, suggesting a possible correlation between HS1,2 alleles and Ig production. To test this, we analyzed levels of serum Igs and HS1,2*A genotypes in two independent cohorts, one of 88 schizophrenic inpatients (24 women) and a second of 133 healthy subjects (59 women). Both groups were similar in the frequency of individuals with altered serum concentration of Ig classes and IgG subclasses (schizophrenia panel-80 percent; controls-68 percent). With the possible exception of a stabilizing effect of olanzapine, no psychopharmacological drug consumed during the month prior to serum sampling in the schizophrenia group significantly affected Ig levels. In both patient and control cohorts, an increased frequency of the HS1,2*2A allele corresponded to increased Ig plasma levels, while an increased frequency of the HS1,2*1A allele corresponded to decreased Ig plasma levels. EMSA analysis with nuclear extracts from human B cells showed that the transcription factor SP1 bound to the polymorphic region of both HS1,2*1A and HS1,2*2A while NF-kB bound only to the HS1,2*2A. We predict that differences in transcription factor binding sites in the two allelic variants of the 3' IgH enhancer HS1,2 may provide a mechanism by which differences in Ig expression are affected.

Association of intracellular pro- and anti-inflammatory cytokines in peripheral blood with the clinical or ultrasound indications for carotid endarterectomy in patients with carotid atherosclerosis.

Early non-invasive diagnostic information would be useful in identifying patients at risk of progressive carotid atherosclerosis, despite an apparently harmless plaque on ultrasound imaging. In this study, we assessed the possible association of intracellular cytokines in peripheral blood with the ultrasound (stenosis > or = 70%) and clinical indications (transient ischaemic attack, amaurosis fugax or stroke) for carotid endarterectomy (CEA) in patients. Intracellular cytokine expression was determined in 106 patients (67 undergoing and 39 not undergoing CEA). Cells primed for the proinflammatory cytokines tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, IL-8 and the anti-inflammatory cytokines IL-4 and IL-10 were found in significantly higher percentages in patients undergoing CEA than in patients who were not (P < 0.05). Intracellular cytokine expression was significantly higher in patients undergoing CEA who had stenosis > or = 70% (TNF-alpha, IFN-gamma, IL-1beta, IL-6, IL-4 and IL-10), with previous stroke (IFN-gamma, IL-1beta, IL-6, IL-8, IL-4 and IL-10) and with amaurosis fugax (IFN-gamma, IL-6, IL-4 and IL-10) than in patients not undergoing CEA. Increased intracellular cytokines in patients' peripheral blood might be a warning signal indicating progressive atherosclerosis. If so, intracellular cytokine monitoring could help in selecting patients at high risk of future clinical cardiovascular events and therefore most likely to benefit from CEA or adjustment of pharmacological therapy.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses.

BACKGROUND: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia. METHODS: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia. RESULTS: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC). CONCLUSIONS: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

The wolframin His611Arg polymorphism influences medication overuse headache.

Homozygosis for wolframin (WFS1) mutations determines Wolfram syndrome (WS), and common polymorphisms of WFS1 are associated with psychiatric illnesses and dependence behaviour. To test the influence of WFS1 polymorphisms on medication overuse headache (MOH), a chronic headache condition related to symptomatic drugs overuse, we analyzed 82 MOH patients for the WFS1 His611Arg polymorphism, and performed a comparison between clinical features of Arg/Arg (R/R) and non-R/R individuals. Individuals harbouring the R/R genotype showed significantly higher monthly drug consumption (t=-3.504; p=0.00075) and more severe depressive symptoms on the BDI questionnaire (t=-3.048; p=0.003) than non-R/R. WFS1 polymorphism emerged as the only significant predictor of drug consumption, at the multivariate regression analysis (F=12.277; d.f.=1,80; p=0.00075, adjusted R2=0.122). These results implicate WFS1 in the clinical picture of MOH, may be through an influence on need for drugs as in other conditions of abuse behaviour.

Immunology of Alveolar and Cystic Echinococcosis (AE and CE).

Cystic and alveolar echinococcosis are severe chronic helminthic diseases caused by the cystic growth or the intrahepatic tumour-like growth of the metacestode of Echinococcus granulosus or Echinococcus multilocularis, respectively. Both parasites have evolved sophisticated strategies to escape host immune responses, mainly by manipulating and directing this immune response towards anergy and/or tolerance. Recent research studies have revealed a number of respective immunoregulatory mechanisms related to macrophages and dendritic cell as well as T cell activities (regulatory T cells, Tregs). A better understanding of this complex parasite-host relationship, and the elucidation of specific crucial events that lead to disease, represents targets towards the development of novel treatment strategies and options.

Cystic echinococcosis: progress and limits in epidemiology and immunodiagnosis.

This study discusses the epidemiology and immunodiagnosis of cystic echinococcosis (caused by Echinococcus granulosus). Despite the development of molecular methods to prepare antigens, nowadays there is no standard, highly sensitive, and specific test available for antibody detection in cystic echinococcosis. Furthermore, because serological tests can give only a limited support to clinical findings there is a clear need for new advances in immunodiagnosis of E. granulosus infection.

Long-term potentiation and memory processes in the psychological works of Sigmund Freud and in the formation of neuropsychiatric symptoms.

Far from disproving the model of mind functioning proposed by psychoanalysis, the recent advances in neuropsychiatrical research confirmed the crucial ideas of Sigmund Freud. The hypothesis that the origin of mental illnesses lies in the impossibility for a subject to erase the long-term effects of a remote adverse event is in tune with the view that several psychiatric disturbances reflect the activation of aberrant unconscious memory processes. Freud's insights did not stop here, but went on to describe in an extremely precise manner the neural mechanisms of memory formation almost a century before the description of long-term synaptic potentiation.

Adversity in childhood and depression: linked through SIRT1.

Experiencing an adverse childhood and parental neglect is a risk factor for depression in the adult population. Patients with a history of traumatic childhood develop a subtype of depression that is characterized by earlier onset, poor treatment response and more severe symptoms. The long-lasting molecular mechanisms that are engaged during early traumatic events and determine the risk for depression are poorly understood. In this study, we altered adult depression-like behavior in mice by applying juvenile isolation stress. We found that this behavioral phenotype was associated with a reduction in the levels of the deacetylase sirtuin1 (SIRT1) in the brain and in peripheral blood mononuclear cells. Notably, peripheral blood mRNA expression of SIRT1 predicted the extent of behavioral despair only when depression-like behavior was induced by juvenile--but not adult--stress, implicating SIRT1 in the regulation of adult behavior at early ages. Consistent with this hypothesis, pharmacological modulation of SIRT1 during juvenile age altered the depression-like behavior in naive mice. We also performed a pilot study in humans, in which the blood levels of SIRT1 correlated significantly with the severity of symptoms in major depression patients, especially in those who received less parental care during childhood. On the basis of these novel findings, we propose the involvement of SIRT1 in the long-term consequences of adverse childhood experiences.

Further evaluation of autoreactive T cells in hydatid patients.

We evaluated the peripheral autoreactive response in patients with Echinococcus granulosus who showed a negative humoral response as compared to seropositive patients and healthy controls. For this purpose, a limiting dilution analysis (LDA) of autologous mixed lymphocyte cultures was established to both estimate frequency of autoreactive T cells and, by analysing the shape of the curves, to clarify the mechanisms that underlie the autoreactive response. Different LDA curves were observed between healthy controls and patients, suggesting that different cell interactions are involved in the two populations. More interestingly, all hydatid patients, independent of their humoral response, showed a higher number of autoreactive T cells than controls. Precisely, subjects with a negative humoral response showed a range of values for autoreactive T cells exactly between the value ranges observed in seropositive and normal subjects. The present data also show that the increase of autoreactive T cells in hydatid patients correlates with the production of specific antibodies.

Cytokine patterns in seropositive and seronegative patients with Echinococcus granulosus infection.

To investigate the involvement of immunological variables, including the Th1/Th2 balance, in the mechanisms underlying seronegativity in cystic echinococcosis (CE), Th1 and Th2 cytokines were evaluated in ELISA determining IFN-gamma, IL-4, -5 and -10 production in peripheral blood mononuclear cell (PBMC) cultures from 16 patients (six seronegative and ten seropositive) with CE and from six healthy donors. Patients who had undetectable antibody levels in their sera invariably produced no IL-5 and scarce IL-4 and -10 (Th2 response); both groups of patients produced similar amounts of IFN-gamma; (Th1 response). The analysis of host clinical features and cyst characteristics shows that these variables do not explain the lack of detectable serum antibody levels. These findings suggest that seronegativity arises because unknown host or parasite factors, or both, cause inadequate Th2 cell activation thus reducing production of Th2 cytokines, including IL-5, the cytokine primarily implicated in immunoglobulin expression in CE.

Molecular and cellular tools in human cystic echinococcosis.

The latest developments in the molecular and cellular mechanisms that underlie Echinococcus infection have renewed interest in the immunodiagnosis of this disease and have helped in understanding the host-parasite relationship. This review discusses current concepts on the immune response to Echinococcus granulosus in humans, and relates these findings to diagnosis and clinical management. The two most promising molecular tools developed for the immunodiagnosis of cystic echinococcosis involve isolating native or recombinant parasite antigens to detect specific serum antibodies in patients with suspected echinococcosis and producing monoclonal antibodies to detect parasite antigens in clinical samples. Novel drugs should be designed to strengthen host immune responses thus combating parasitic survival. Currently, attention has been focused on understanding T-helper lymphocyte activity; in particular the role of Th1 and Th2 subsets in orchestrating immune responses. The Th1/Th2 model explaining how selective immune responses--including cell-mediated or humoral immunity--develop, seems promising as the rationale for molecular tools that could lead to new therapeutic strategies.

Diagnosis of Pneumocystis carinii pneumonia: specificity and sensitivity of polymerase chain reaction in comparison with immunofluorescence in bronchoalveolar lavage specimens.

DNA amplification by the polymerase chain reaction (PCR) is a promising method for the detection of Pneumocystis carinii in immunosuppressed patients. The sensitivity and specificity of the PCR technique has been assessed in comparison with the immunofluorescence method (IF) on bronchoalveolar lavage fluid (BALF). Results correlated in 43 (78.8%) of 52 cases studied. P. carinii PCR gave positive results with BALF from all 32 patients found to have P. carinii pneumonia (PCP); IF gave positive results with 26 of them. PCR was more sensitive and as specific as IF. However, at the present time, we do not believe that it is clinically useful for detection of P. carinii in BALF samples. P. carinii DNA amplification by PCR should be reserved for testing IF-negative BALF samples from patients judged clinically to have PCP.

Imbalance between Pneumocystis carinii cysts and trophozoites in bronchoalveolar lavage fluid from patients with pneumocystosis receiving prophylaxis.

Detection and quantification of different Pneumocystis carinii (PC) life cycle forms were performed by polymerase chain reaction (PCR) and by morphological stains on bronchoalveolar lavage fluids (BALF) from HIV-infected patients with P. carinii pneumonia (PCP). The number of PC trophozoites was higher in patients with PCP who were receiving prophylaxis than in those not receiving prophylaxis. Also the cyst: trophozoite ratio was lower in the first group. No difference was observed between patients receiving different prophylactic medications. The imbalance between PC forms in BALF from patients with PCP receiving anti-PC prophylaxis may hamper the sensitivity of cyst stains. Multiple stains or PCR examination should be performed on BALF from patients with clinically suspected PCP who are receiving prophylaxis.

Potential impact of Pneumocystis genetic diversity on the molecular detection of the parasite in human host.

Our aim was to evaluate if genetic diversity of Pneumocystis carinii could influence the detection by molecular techniques in bronchoalveolar lavage (BAL) fluids and in non-invasive specimens (induced sputum, oropharyngeal washing and serum/blood). P. carinii is morphologically similar in different hosts although several strains have been identified by biomolecular techniques. Variations of mt-LSU and ITSs sequences could determine a lack of hybridization of some clinical samples and could have diagnostic consequences with loss in sensitivity and specificity of available molecular tests, but at the moment no data support a significant impact of genetic diversity in these sequences on molecular detection of P. carinii for clinical purposes.