Early maladaptive schemas and suicidal risk in inpatients with bipolar disorder

The present study aimed to assess the associations of early maladaptive schemas (EMSs) and clinical factors (hypomanic/manic and depressive symptoms) with suicidal risk (current suicidal ideation and lifetime suicide attempts) in inpatients with bipolar disorder (BD). One hundred inpatients with BD completed the Young Schema Questionnaire-Short Form (YSQ-SF), the Bipolar Depression Rating Scale (BDRS), the Young Mania Rating Scale (YMRS), and the Beck Scale for Suicide Ideation (BSSI). 59 of patients had lifetime suicide attempts and 59 showed high suicidal risk (BSSI>/=6). BD patients with lifetime suicide attempts had higher scores on the entitlement and social isolation schemas, depression, and hypomanic/manic symptoms than those without such attempts. Patients with high suicidal risk had higher levels of depressive and hypomanic/manic symptoms as well as some EMSs than those without high suicidal risk. Logistic regression analyses revealed that hypomanic/manic symptoms as well as the entitlement and defectiveness schemas were significantly associated with current suicidal ideation. Also, the entitlement and social isolation schemas were associated with lifetime suicide attempts. These results suggest that the entitlement, social isolation, and defectiveness schemas may relate to suicidal risk in patients with BD

Prion Protein Is a Key Determinant of Alcohol Sensitivity through the Modulation of N-Methyl-D-Aspartate Receptor (NMDAR) Activity

The prion protein (PrP) is absolutely required for the development of prion diseases; nevertheless, its physiological functions in the central nervous system remain elusive. Using a combination of behavioral, electrophysiological and biochemical approaches in transgenic mouse models, we provide strong evidence for a crucial role of PrP in alcohol sensitivity. Indeed, PrP knock out (PrP−/−) mice presented a greater sensitivity to the sedative effects of EtOH compared to wild-type (wt) control mice. Conversely, compared to wt mice, those over-expressing mouse, human or hamster PrP genes presented a relative insensitivity to ethanol-induced sedation. An acute tolerance (i.e. reversion) to ethanol inhibition of N-methyl-D-aspartate (NMDA) receptor-mediated excitatory post-synaptic potentials in hippocampal slices developed slower in PrP−/− mice than in wt mice. We show that PrP is required to induce acute tolerance to ethanol by activating a Src-protein tyrosine kinase-dependent intracellular signaling pathway. In an attempt to decipher the molecular mechanisms underlying PrP-dependent ethanol effect, we looked for changes in lipid raft features in hippocampus of ethanol-treated wt mice compared to PrP−/− mice. Ethanol induced rapid and transient changes of buoyancy of lipid raft-associated proteins in hippocampus of wt but not PrP−/− mice suggesting a possible mechanistic link for PrP-dependent signal transduction. Together, our results reveal a hitherto unknown physiological role of PrP on the regulation of NMDAR activity and highlight its crucial role in synaptic functions

The diagnostic suitability of a xerostomia questionnaire and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents

The study objective was to explore the diagnostic suitability of the Xerostomia Inventory and the association between xerostomia, hyposalivation and medication use in a group of nursing home residents. A cross-sectional study was carried out in 50 physically impaired nursing home residents (20 men) with a mean age of 78.1 years (range, 53–98) in The Netherlands. The Xerostomia Inventory-Dutch version was completed for all residents and the data were subjected to exploratory factor analysis to determine the diagnostic suitability. Residents’ data on xerostomia, whole saliva secretion rates and hyposalivation-related medications used were collected and statistically analyzed. The diagnostic suitability of the Xerostomia Inventory-Dutch version appeared restricted. The prevalence of xerostomia was 52%, without gender and age difference. The prevalence of hyposalivation was 24% for resting, 60% for chewing-stimulated and 18% for acid-stimulated whole saliva. All whole saliva secretion rates were significantly lower in women than in men and in older than in younger residents. Forty-four percent of all medications used were hyposalivation-related and women used significantly more medications than men. Xerostomia was significantly negatively correlated with the resting whole saliva secretion rate. The number of hyposalivation-related medications used was not significantly correlated with the various whole saliva secretion rates. In nursing home residents, xerostomia, hyposalivation and using hyposalivation-related medications seem common and partially associated features

Exacerbation of experimental autoimmune encephalomyelitis in prion protein (PrPc)-null mice: evidence for a critical role of the central nervous system

<p>Abstract</p> <p>Background</p> <p>The cellular prion protein (PrPc) is a host-encoded glycoprotein whose transconformation into PrP scrapie (PrPSc) initiates prion diseases. The role of PrPc in health is still obscure, but many candidate functions have been attributed to the protein, both in the immune and the nervous systems. Recent data show that experimental autoimmune encephalomyelitis (EAE) is worsened in mice lacking PrPc. Disease exacerbation has been attributed to T cells that would differentiate into more aggressive effectors when deprived of PrPc. However, alternative interpretations such as reduced resistance of neurons to autoimmune insult and exacerbated gliosis leading to neuronal deficits were not considered.</p> <p>Method</p> <p>To better discriminate the contribution of immune cells versus neural cells, reciprocal bone marrow chimeras with differential expression of PrPc in the lymphoid or in the central nervous system (CNS) were generated. Mice were subsequently challenged with MOG_35-55peptide and clinical disease as well as histopathology were compared in both groups. Furthermore, to test directly the T cell hypothesis, we compared the encephalitogenicity of adoptively transferred PrPc-deficient versus PrPc-sufficient, anti-MOG T cells.</p> <p>Results</p> <p>First, EAE exacerbation in PrPc-deficient mice was confirmed. Irradiation exacerbated EAE in all the chimeras and controls, but disease was more severe in mice with a PrPc-deleted CNS and a normal immune system than in the reciprocal construction. Moreover, there was no indication that anti-MOG responses were different in PrPc-sufficient and PrPc-deficient mice. Paradoxically, PrPc-deficient anti-MOG 2D2 T cells were less pathogenic than PrPc-expressing 2D2 T cells.</p> <p>Conclusions</p> <p>In view of the present data, it can be concluded that the origin of EAE exacerbation in PrPc-ablated mice resides in the absence of the prion protein in the CNS. Furthermore, the absence of PrPc on both neural and immune cells does not synergize for disease worsening. These conclusions highlight the critical role of PrPc in maintaining the integrity of the CNS in situations of stress, especially during a neuroinflammatory insult.</p

Functionally Relevant Domains of the Prion Protein Identified In Vivo

The prion consists essentially of PrPSc, a misfolded and aggregated conformer of the cellular protein PrPC. Whereas PrPC deficient mice are clinically healthy, expression of PrPC variants lacking its central domain (PrPΔCD), or of the PrP-related protein Dpl, induces lethal neurodegenerative syndromes which are repressed by full-length PrP. Here we tested the structural basis of these syndromes by grafting the amino terminus of PrPC (residues 1–134), or its central domain (residues 90–134), onto Dpl. Further, we constructed a soluble variant of the neurotoxic PrPΔCD mutant that lacks its glycosyl phosphatidyl inositol (GPI) membrane anchor. Each of these modifications abrogated the pathogenicity of Dpl and PrPΔCD in transgenic mice. The PrP-Dpl chimeric molecules, but not anchorless PrPΔCD, ameliorated the disease of mice expressing truncated PrP variants. We conclude that the amino proximal domain of PrP exerts a neurotrophic effect even when grafted onto a distantly related protein, and that GPI-linked membrane anchoring is necessary for both beneficial and deleterious effects of PrP and its variants

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Psychometric properties of the persian versions of the Positive Alcohol Metacognitions Scale (Persian-PAMS) and the Negative Alcohol Metacognitions Scale (persian-NAMS) in alcoholdependent individuals

Positive and negative metacognitions regarding alcohol effects are related to drinking problems. This study aimed to validate the Persian versions of the Positive Alcohol Metacognitions Scale (Persian-PAMS) and the Negative Alcohol Metacognitions Scale (Persian-NAMS) and to assess the relations of metacognitions about alcohol use to alcohol craving and dependence in a clinical sample of males with a DSM diagnosis of alcohol dependence. Three hundred treatment-seeking males with alcohol dependence completed the Alcohol Use Disorders Identification Test (AUDIT), the Alcohol Outcome Expectancy Questionnaire (AOEQ), the Obsessive Compulsive Drinking Scale (OCDS), the Depression Anxiety Stress Scales (DASS-21), and the Persian-translated versions of the PAMS and NAMS. The results showed that similar to original versions of the PAMS and NAMS, the Persian version of the scales had a two-factor structure. Test-retest coefficients over a fourweek interval and internal consistency showed good reliability for the Persian-PAMS and Persian-NAMS and their subscales. Predictive validity showed that positive metacognitions about alcohol use were associated with alcohol craving and dependence independent of outcome expectancies about alcohol use. The findings suggest that the Persian-PAMS and Persian-NAMS have appropriate psychometric properties in Iranian males with alcohol dependence. Results also highlight that positive metacognitions may be more related to alcohol craving and dependence relative to outcome expectancies about alcohol use

Alexithymia influences craving through facets of emotion regulation in alcoholic patients

There is evidence that alexithymia is related to alcohol problems. However, no study has been conducted to show whether emotion regulation (ER) subscales such as reappraisal and suppression mediate the relationship between alexithymia and craving. The aim of this study was to evaluate the effects of ER subscales (i. e., reappraisal and suppression) as mediators on the relationships between alexithymia and subscales of craving (i. e., obsessive and compulsive subscales). A total of 205 alcoholic outpatients completed the Farsi version of the Toronto Alexithymia Scale (FTAS-20), the Emotion Regulation Questionnaire (ERQ), the Obsessive Compulsive Drinking Scale (OCDS), the Alcohol Use Disorders Identification Test (AUDIT), and the Beck Depression Inventory-II (BDI-II). Results revealed that alexithymia indirectly influenced obsessive and compulsive cravings through both paths of ER decreased reappraisal and increased suppression subscales. Also, the relations of alexithymia to obsessive and compulsive cravings through the mediation pathway of decreased reappraisal were stronger than the path of suppression. It was concluded that low reappraisal and high suppression seem to be important in predicting obsessive and compulsive cravings for alcoholics with alexithymia. This suggests that the efforts based on increasing reappraisal and decreasing suppression may be important in reducing craving in alcoholic patients

Difficulties in emotion regulation mediate negative and positive affects and craving in alcoholic patients

The aim of this study was to assess the mediating effects of difficulties in emotion regulation (DER) on the relations of negative and positive affects to craving in alcoholic patients. 205 treatment-seeking alcoholic outpatients were included. DER, positive and negative affects as well as craving were evaluated by the Difficulties in Emotion Regulation Scale (DERS), the Positive/Negative Affect Scales, and the Obsessive Compulsive Drinking Scale (OCDS) respectively. Clinical factors including depression and severity of alcohol dependence were investigated by the Alcohol Use Disorders Identification Test (AUDIT) and the Beck Depression Inventory-II (BDI-II) respectively. Results revealed that both increased negative affect and decreased positive affect indirectly influenced craving through limited access to emotion regulation strategies. It was concluded that limited access to emotion regulation strategies may be important in predicting craving for alcoholics who experience both increased negative affect and decreased positive affect. This suggests that treatment and prevention efforts focused on increasing positive affect, decreasing negative affect and teaching effective regulation strategies may be critical in reducing craving in alcoholic patients. (C) 2017 Elsevier Ltd. All rights reserved