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Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.
To identify factors associated with suicide attempts using data from a large, 3-year, multinational follow-up study of schizophrenia (SOHO study).
All baseline characteristics of 8,871 adult patients with schizophrenia collected in patients included in the SOHO study were included in a GEE logistic regression post-hoc analysis comparing patients who attempted suicide during the study with those who did not.
A total of 384 (4.3%) patients attempted or committed suicide. The risk factors that resulted statistically associated with suicide attempt were a lifetime history of suicide attempts (OR 3.6 [95% CI 2.8, 4.6; p< 0.0001]), suicide attempts in the last 6 months (OR 2.5 [95% CI 1.8, 3.4; p< 0.0001]), prolactin-related side effects (OR 2.0 [95%CI 1.4, 2.9; p=0.0002]), CGI depression (OR 1.2 [95% CI 1.1, 1.3; p=0.0004]) and history of hospitalization for schizophrenia (OR 1.4 [95% CI 1.1, 1.8; p=0.009]).
In view of the observational design of the study and the post-hoc nature of the analysis, the identified risk factors should be confirmed by ad-hoc specifically designed studies.
Treatment of schizophrenia with antipsychotic drugs is frequently sub-optimal. One reason for this may be heterogeneity between patients with schizophrenia. The objectives of this study were to identify patient, disease and treatment attributes that are important for physicians in choosing an antipsychotic drug, and to identify empirically subgroups of patients who may respond differentially to antipsychotic drugs. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients with schizophrenia. Information on 39 variables was collected. Multiple component analysis was used to identify dimensions that explained the variance between patients. Three axes, accounting for 99% of the variance, were associated with disease severity (64%), socioeconomic status (27%) and patient autonomy (8%). These dimensions discriminated between six discrete patient subgroups, identified using ascending hierarchical classification analysis. The six subgroups differed regarding educational level, illness severity, autonomy, symptom presentation, addictive behaviors, comorbidities and cardiometabolic risk factors. Subgroup 1 patients had moderately severe physician-rated disease and addictive behaviours (23.2%); Subgroup 2 patients were well-integrated and autonomous with mild to moderate disease (6.7%); Subgroup 3 patients were less well-integrated with mild to moderate disease, living alone (11.2%); Subgroup 4 patients were women with low education levels (5.4%), Subgroup 5 patients were young men with severe disease (36.8%); and Subgroup 6 patients were poorly-integrated with moderately severe disease, needing caregiver support (16.7%). The presence of these subgroups, which require confirmation and extension regarding potentially identifiable biological markers, may help individualizing treatment in patients with schizophrenia.
Schizophrenia is a frequent psychiatric disorder whose prevalence appears to be relatively stable across different patient groups. However, attitudes to care and resources devoted to mental health care may differ between countries. The objective of this analysis was to compare sociodemographic and psychopathological features of patients, antipsychotic treatment and frequency of hospitalisation between four European countries (Germany, Greece, Italy and Spain) collected as part of a large survey of the characteristics of patients with schizophrenia. The survey was conducted by structured interview of 744 randomly-selected psychiatrists in four European countries who recruited 3996 patients. Information on 39 variables was collected. A number of between-country differences were observed which tended to distinguish Germany on the one hand, from the Mediterranean countries, and Greece in particular, on the other. While demographic features and clinical features were essentially similar, more patients in Germany were considered to have severe disease by their psychiatrist (59.0% versus 35.9% in Greece) and to be hospitalised (49.3% versus 15.0%). 46.7% of German patients were living alone compared to less than 20% in the Mediterranean countries and 50.2% were living with their family (versus over70% elsewhere). Smoking and addictive behaviours were more frequently reported for patients in Spain. With regard to empirically derived patient subgroups, Subgroup 2, corresponding to well-integrated and autonomous patients with mild to moderate disease severity was most highly represented in Greece (23.6% of patients compared to less than 10% elsewhere) elsewhere, Subgroup 6 (poorly-integrated patients with moderately severe disease who require caregiver support) was under-represented in Germany (4.5% versus over 17% elsewhere). Patterns of treatment were essentially similar, although quetiapine was more frequently prescribed and paliperidone less frequently prescribed in Germany than elsewhere. Reasons for treatment choice were comparable between countries, primarily related to good tolerability and control of positive symptoms. The differences observed may be attributed to differences in mental health care resource provision, socio-cultural or educational differences or to resource issues.
White matter abnormalities play a prominent role in the pathogenesis of schizophrenia. Diffusion tensor imaging (DTI) studies showed a widespread decrease in fractional anisotropy (FA) in psychotic disorders.
To examine white and grey matter abnormalities in first episode psychosis (FEP).
We obtained T1-weighted and DTI magnetic resonance images (1.5 T) from 8 right-handed drug-naïve FEP patients and 8 healthy controls. The DTI data set was used to calculate FA maps; we carried-out optimized voxel-based morphometry (VBM) analysis of grey matter (GM) and FA maps using SPM2.
Patients were assessed with a neuropsychological battery comprising the Trail Making Test, the Stroop Colour Word Test, the Wisconsin Card Sorting Test and a test of Facial Affect recognition.
The voxelwise analysis showed decreased FA in the superior longitudinal and inferior fronto-occipital fasciculi, bilaterally, and in the left uncinate fasciculus. We observed reduced GM volume in the left frontal cortex (Brodmann areas [BA] 47, 13, 11, 10, and 9) and in right frontal (BA6), temporal (BA34) and occipital (BA 18, 19, and 30) cortex.
Neuropsychological assessment showed impaired executive function and deficit in facial affect recognition.
Our findings showed fronto-temporal disconnectivity in FEP and structural alterations in both cortical and subcortical regions.
Neuroanatomical findings are consistent with patients’ neuropsychological performance.
Further studies to establish a relationship between white and grey matter disarray on one hand and neuropsychological testing are needed.
The stigmatisation of the psychiatric patient is still a strong barrier to the integration process of these subjects in our society. Therefore, it is necessary to identify what types of prejudices exist and the types of variables with which they are linked, in order to plan strategies to reduce them. In this exploratory study we administered a semi-structured interview to 303 subjects in order to examine the relationships between social attitudes towards mental disorders and some social demographic variables, the information about mental disorders and the previous ‘contacts’ with psychiatric patients.
The data analysis shows that there is a relationship between knowledge of psychiatric patients and a more positive attitude towards them (i.e., less fear, more integration and work opportunities). This study is to be considered preliminary as far as people’s attitudes towards psychiatric patients are concerned. This result encourages the planning and implementation of sensitisation and information programs concerning mental disorders, in the sense that increasing the knowledge of mental disorders could lead to significant achievements in the important fight against the stigma surrounding psychiatric patients.
Enkephalin is an opioidergic neuromodulator that has been implicated in long-term behavioural sensitization after administration of drugs of abuse. Enkephalin is also a molecular marker of GABAergic neurons in the striato-pallidal pathway that is involved in sensory-motor gating and has been considered dysfunctional in the pathophysiology of psychosis.
In this study we investigated in male Sprague Dawley rats putative changes in Enkephalin transcripts by in situ hybridization after acute or subchronic administration of ketamine in either high or low subanaesthetic doses (50 mg/kg and 12 mg/kg respectively). Ketamine is a non-competitive NMDA-R antagonist that perturbs glutamate neurotransmission and provides a preclinical model of psychosis-like behaviour in rats.
In the acute paradigm the expression of Enkephalin was reduced in the motor, premotor, somatosensory cortices as well as in anterior cingulate. In the subchronic paradigm Enkephalin expression was reduced in the premotor cortex, in the ventromedial caudate-putamen and in the shell of nucleus accumbens. Comparative analysis showed that the relative decrement in gene expression was not significantly different between the acute and subchronic paradigm for each region of interest.
Changes in distribution of Enkephalin expression and correlation analysis of functionally related brain regions suggest that Enkephalin transcripts reduction may be implicated in the motivational aspects of drug addiction and may help explaining some aspects of the pathophysiology in ketamine-induced psychosis.
The Brief Negative Symptom Scale (BNSS) was developed to address the main limitations of the existing scales for the assessment of negative symptoms of schizophrenia. The initial validation of the scale by the group involved in its development demonstrated good convergent and discriminant validity, and a factor structure confirming the two domains of negative symptoms (reduced emotional/verbal expression and anhedonia/asociality/avolition). However, only relatively small samples of patients with schizophrenia were investigated. Further independent validation in large clinical samples might be instrumental to the broad diffusion of the scale in clinical research.
The present study aimed to examine the BNSS inter-rater reliability, convergent/discriminant validity and factor structure in a large Italian sample of outpatients with schizophrenia.
Our results confirmed the excellent inter-rater reliability of the BNSS (the intraclass correlation coefficient ranged from 0.81 to 0.98 for individual items and was 0.98 for the total score). The convergent validity measures had r values from 0.62 to 0.77, while the divergent validity measures had r values from 0.20 to 0.28 in the main sample (n = 912) and in a subsample without clinically significant levels of depression and extrapyramidal symptoms (n = 496). The BNSS factor structure was supported in both groups.
The study confirms that the BNSS is a promising measure for quantifying negative symptoms of schizophrenia in large multicenter clinical studies.
Individual social capital has been recognized as having an important role for health and well-being. We tested the hypothesis that poor social capital increases internalized stigma and, in turn, can reduce empowerment among people with major depressive disorder (MDD).
Materials and methods:
This is a cross-sectional multisite study conducted on a sample of 516 people with MDD in 19 European countries. Structural Equation Models were developed to examine the direct and indirect effects of self-stigma and social capital on empowerment.
Social capital and self-stigma accounted for 56% of the variability in empowerment. Higher social capital was related to lower self-stigma (r = –0.72, P < 0.001) which, in turn, partially mediated the relationship between social capital and empowerment (r = 0.38, P < 0.001).
Social capital plays a key role in the appraisal of empowerment, both directly and through the indirect effect mediated by self-stigma. In order to improve empowerment of people with MDD, we identify strategies to foster individual social capital, and to overcome the negative consequences related to self-stigma for attainment of life goals.
Borderline personality disorder (BPD) is a chronic condition with a strong impact on patients’ affective, cognitive and social functioning. Neuroimaging techniques offer invaluable tools to understand the biological substrate of the disease. We aimed to investigate gray matter alterations over the whole cortex in a group of Borderline Personality Disorder (BPD) patients compared to healthy controls (HC).
Magnetic resonance-based cortical pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD patients and in their age- and sex-matched HC (age: 38 ± 11; females: 16, 61%).
BPD patients showed widespread lower cortical GMD compared to HC (4% difference) with peaks of lower density located in the dorsal frontal cortex, in the orbitofrontal cortex, the anterior and posterior cingulate, the right parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and in the visual cortex (P < 0.005). Our BPD subjects displayed a symmetric distribution of anomalies in the dorsal aspect of the cortical mantle, but a wider involvement of the left hemisphere in the mesial aspect in terms of lower density. A few restricted regions of higher density were detected in the right hemisphere. All regions remained significant after correction for multiple comparisons via permutation testing.
BPD patients feature specific morphology of the cerebral structures involved in cognitive and emotional processing and social cognition/mentalization, consistent with clinical and functional data.
Many patients with schizophrenia show major difficulties in performing basic social roles. Occupational and social functioning (and independent living) are considered domains of functioning. Improvement in functioning is recognized as an important aim in treatment guidelines and as an outcome by regulatory agencies.
The Europe, Middle East and Africa (EMEA) functioning survey canvassed opinions of psychiatrists (and neurologists with psychiatric backgrounds in Germany) across the region.
To ascertain psychiatrists' perceptions of the clinical importance, assessment and management of functioning amongst their patients with schizophrenia.
The survey comprised 17 questions and was conducted from March-April 2011, in 39 EMEA countries. Respondents' demographics and their opinions regarding personal and social functioning in patients with schizophrenia were collected.
Results were obtained from 3610 clinicians. Psychiatrists reported that they perceived more than two in three of their patients show impaired/very poor levels of functioning. 91% believed that personal and social functioning was an important treatment goal for patients with schizophrenia and 90% believed it was an important goal for patients' families. The majority of psychiatrists assess the personal and social functioning of their patient at each visit but 81% determine the level of functioning through clinical interview. To manage personal and social functioning in their patients, 26% of psychiatrists prefer pharmacological interventions while 47% prefer psychosocial interventions.
Although psychiatrists recognize that functioning is impaired/very poor in patients with schizophrenia, there is still a need to address it as a main treatment goal for patients with schizophrenia.
Post-traumatic Stress Disorder (PTSD) has demonstrated gender-specific prevalence and expressions across the different DSM definitions, since its first introduction in DSM-III. The DSM-5 recently introduced important revisions to PTSD symptomatological criteria. Aim of the present study is to explore whether gender moderates rates of DSM-5 PTSD expression in a non-clinical sample of survivors to a massive earthquake in Italy.
A sample of 450 survivors of the L’Aquila 2009 earthquake, previously investigated for the presence DSM-IV-TR PTSD, was reassessed according to DSM-5 criteria in order to explore gender differences. All subjects completed the Trauma and Loss Spectrum-Self Report (TALS-SR).
Females showed significantly higher DSM-5 PTSD rates and rates of endorsement of almost all DSM-5 PTSD criteria. Significant gender differences emerged in almost half of PTSD symptomatological criteria with women reporting higher rates in almost half of them, while men in only one (a new symptom in DSM-5: reckless or self-destructive behavior). Considering the impact of the three new DSM-5 symptoms on the diagnosis, significant gender differences emerged with these being crucial in almost half of the PTSD diagnoses in males but in about onefourth in females.
This study provides a contribution to the ongoing need for reassessment on how gender moderates rates of expression of particular disorders such as PTSD.
A large body of research has shown that Oxytocin (OXT) is an important prosocial peptide and there is also initial evidence that the central OXT system is altered in several mental disorders that are characterized by severe social disturbances and deficits, such as anxiety disorders disorders with prominent social dysfunction (e.g., schizophrenia) mood disorders and borderline personality disorder. In particular, Feifel et al. (2010) and Pedersen et al (2011) recently conducted two randomized, placebo-controlled study of intranasal oxytocin in schizophrenia patients to test the hypothesis that oxytocin can reduce symptoms of this disorder. Their results support the hypothesis that oxytocin may reduce psychotic symptoms and may diminish certain social cognition deficits that are not improved by current antipsychotic medications.
to review the main studies conducted on oxytocin and its relation with mental disorders.
We will present a systematic review on the studies conducted on oxytocin and mental disorder, both in non-clinical and in clinical samples. In order to overcome some of the limitations of the previous studies, we will present a study which is going to be run, aimed at testing whether the intranasal administration of the neuropeptide oxytocin as adjunct to antipsychotic treatment improves positive and negative symptoms its effect on social cognition, social functioning and empathy in patients with schizophrenia.
Bipolar patients are at higher risk for cardiovascular morbidity and mortality than their counterparts in the general population. In a recent in vitro study, Asenapine, a new antipsychotic for the treatment of mania/mixed mania, was found to keep physiological endothelial function by activation of eNOS-related NO release and to protect endothelial cells against peroxidation by interference with mitochondria, apoptosis and cell survival.
To examine the cardiac protective effects elicited by Asenapine against peroxidation and on the Ca2+ movements.
In HL-1 that had undergone oxidative stress by 20 min hydrogen peroxide the effects of 30 min pre-treatment with Asenapine on survival and proliferation will be examined. In Fura-2AM loaded HL-1 we will next analyze the effects of Asenapine on Ca2+ movements and the related involvement of cAMP/PKA and PLC pathways, CaMKII, L and T type Ca2+ channels and 5HT1A receptors. The role of ‘capacitative” Ca2+ entry, plasma-membrane Ca2+ pump inhibitor (PMCA) and Na+/Ca2+ exchanger will be analyzed. Changes of membrane potential caused by interference with K+ channels will be examined, as well.
We expect to find a proliferative and anti-peroxidative effect of Asenapine in HL-1 cells. Asenapine could also affect Ca2+ movements through cAMP/PKA and PLC-dependent signalling and the involvement of 5HT1A receptors. The effects of Asenapine could also be related to changes of plasma membrane by interference with K+ channels and the modulation of PMCA activity and Na+/Ca2+ exchanger.
We expect to further confirm the protective effect of Asenapine against peroxidative injuries. Implications will be discussed
The Consultation-Liaison Psychiatry Service of the Modena General Hospital collaborates regularly with the Cardiology Clinic, within the Woman Wellness Project (WWP). Aim of this collaboration is detection and prevention of post-menopausal correlated diseases, including psychiatric syndromes.
To investigate the association between cardiovascular risk factors (BMI, blood pressure, hyperglycemia, hypertrygliceridemia) and psychiatric symptoms in peri-post menopausal.
Ecological study. Data between January 2008 and December 2012 were collected. Correlations, logistic regessions and categorial regressions were performed with STATA.
675 outpatients attended the WWP. 90 (13.3%) were referred to the psychiatrist; 9 refused the examination. Of the remaining 57.7% had a positive psychiatric history and 22.03% already receaved a psychiatric therapy. 40.6% had at least two medical diseases, mainly: overweight (54.2%), hypertension (40.7%) and dyslipidemia (49.1%). After psychiatric consultation emerged that: 11.9% had anxiety symptoms, 27.1% had depressive symptoms and 47.5% presented both anxiety and depressive symptoms. Only 7 patients (11.9%) had a negative psychiatric examination. The regression analysis pointed out no significant association between the cardiometabolic risk-factors and the psychiatric symptomatology. Differently, the outcome at the end of the psychiatric consultation was associated with BMI (r = −.26; p = .05) and heart rate (r = .33; p = .01).
Heart rate and BMI emerge as factors associated with the psychiatric symptomatology presented by the patient. This finding is consistent with previous researches. The absence of significant associations at the regression analysis could be explained by the small sample considered in the present study.
PERDOVE study is a prospective observational cohort study, which providing follow-up at one year, aims to investigate the socio-demographic and clinical characteristics of patients in in the 23 medium-long term RFs of the St John of God Order.
(1) To describe the sociodemographic, clinical, and treatment-related characteristics of RF-patients during an index period in 2010;
(2) to identify predictors and characteristics associated with discharge at 1-year follow-up;
(3) to evaluate clinicians’ predictions about each patient's likelihood of Home Discharge (HD).
All patients staying in September 2010 with a primary psychiatric diagnosis received a set of standardized assessment instruments, including a “Patient Schedule”, BPRS, HONOS, PSP, PHI, and SLOF. Detailed socio-demographic and clinical data were also collected. Logistic regression analyses were run to identify independent discharge predictors.
The study involved 403 patients. 66,7% is male, mean age is 49 (±10). 70.7% is unmarried. The average duration of illness of these patients is 23 years. Primary diagnosis is represented by schizophrenic spectrum disorders (67.5%). At 1 year follow-up, 104 patients (25.8%) were discharged: 13.6% to home, 8.2% to other RFs, 2.2% to supported housing, and 1.5% to prison.
The main variables associated with a higher likelihood of being discharge to home were: to have an illness duration of less than 15 years and to have an available and effective social support in the last year. Lower severity of psychopathology, and higher working skills were also associated with a significantly higher likelihood to be discharged to home.