Quality of Web-based information on obsessive compulsive disorder.

BACKGROUND: The Internet is increasingly used as a source of information for mental health issues. The burden of obsessive compulsive disorder (OCD) may lead persons with diagnosed or undiagnosed OCD, and their relatives, to search for good quality information on the Web. This study aimed to evaluate the quality of Web-based information on English-language sites dealing with OCD and to compare the quality of websites found through a general and a medically specialized search engine. METHODS: Keywords related to OCD were entered into Google and OmniMedicalSearch. Websites were assessed on the basis of accountability, interactivity, readability, and content quality. The "Health on the Net" (HON) quality label and the Brief DISCERN scale score were used as possible content quality indicators. Of the 235 links identified, 53 websites were analyzed. RESULTS: The content quality of the OCD websites examined was relatively good. The use of a specialized search engine did not offer an advantage in finding websites with better content quality. A score ≥16 on the Brief DISCERN scale is associated with better content quality. CONCLUSION: This study shows the acceptability of the content quality of OCD websites. There is no advantage in searching for information with a specialized search engine rather than a general one. Practical implications: The Internet offers a number of high quality OCD websites. It remains critical, however, to have a provider-patient talk about the information found on the Web.

Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.

Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases.

Anxiety and Psychological Stress Before Prenatal Screening in First-Time Mothers Who Conceived Through IVF/ICSI or Spontaneously.

Mothers' general anxiety, anxiety about the well-being of the child and psychological stress before prenatal testing was studied by comparing women who conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with women who conceived naturally. Before the first trimester screening test for Down's syndrome, a group of 51 women who conceived through IVF/ICSI and a group of 54 women who conceived spontaneously completed the State Scale of the State-Trait Anxiety Inventory (S-Anxiety; Spielberger, 1983), the Fear of Bearing a Physically or Mentally Handicapped Child Subscale of the Pregnancy-related Anxiety Questionnaire (PRAQ-R; Huizink et al., 2004), the Psychological Stress Measure (PSM; Lemyre & Tessier, 1988), and the Prenatal Psychosocial Profile (PPP; Curry, Campbell, & Christian, 1994). Women who conceived through IVF/ICSI had more elevated levels of general anxiety and psychological stress than the women who conceived naturally; however, no difference was observed between the two groups for anxiety specifically related to the health of the child. These results underline the need to monitor women's emotional state after conception via IVF/ICSI-when counseling usually ends-and around the time of the first trimester screening. Counseling might thus be extended.

Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution.

BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias. CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

Epstein-Barr virus-related post-transplant lymphoproliferative disorder in solid organ transplant recipients.

Epstein-Barr virus (EBV) contributes to the pathogenesis of post-transplant lymphoproliferative disease (PTLD) in more than 70% of cases. EBV DNAemia surveillance has been reported to assist in the prevention and treatment of PTLD in hematopoietic stem-cell transplantation (HSCT) recipients. Derived from experience in HSCT and taking into account that PCR-based EBV monitoring techniques are currently available in most solid organ transplant (SOT) centres, there is a great interest in EBV surveillance and prevention of PTLD in SOT recipients. In the present document we have tried to address from a practical perspective different important topics regarding the prevention and management of EBV-related PTLD in SOT. To this end, available information on SOT was analysed and combined with potentially useful data from HSCT and expert observations. The document is therefore structured according to different specific questions, each of them culminating in a consensus opinion of the panel of European experts, grading the answers according to internationally recognized levels of evidence. The addressed issues were grouped under the following topics. (i) Timing and epidemiological data of PTLD. Prophylaxis guided by clinical risk factors of early and late PTLD in SOT. (ii) Relationship of EBV DNAemia load monitoring and the development of PTLD in solid organ transplant recipients. (iii) Monitoring of EBV DNAemia after SOT. Which population should be monitored? What is the optimal timing of the monitoring? (iv) Management of SOT recipients with persistent and/or increasing EBV DNAemia.

Change in defense mechanisms and coping over the course of short-term dynamic psychotherapy for adjustment disorder.

Short-term dynamic psychotherapy (STDP) has rarely been investigated with regard to its underlying mechanisms of change, even if psychoanalytic theory informs us about several potential putative mechanisms of change in patients. Change in overall defensive functioning is one. In this study, we explored the role of overall defensive functioning, by comparing it on the process level with the neighbouring concept of overall coping functioning. A total of N=32 patients, mainly presenting adjustment disorder, were included in the study. The patients underwent STDP up to 40 sessions; three sessions per psychotherapy were transcribed and analyzed by using two observer-rating scales: Defense Mechanism Rating Scales (Perry, 1990) and Coping Action Patterns (Perry, Drapeau, Dunkley, & Blake, 2005). Hierarchical linear modeling was applied to model the change over the course of therapy and relate it to outcome. Results suggest that STDP has an effect on the target variable of overall defensive functioning, which was absent for overall coping functioning. Links with outcome confirm the importance of the effect. These results are discussed from methodological and clinical viewpoints.

Change in biased thinking in a 10-session treatment for borderline personality disorder: Further evidence of the motive-oriented therapeutic relationship.

Abstract Borderline Personality Disorder (BPD) is characterized by both maladaptive thinking and problematic schemas. Kramer and colleagues (2011) showed that using the motive-oriented therapeutic relationship (MOTR), based on the individualized understanding of the patient according to Plan Analysis (Caspar, 2007), can improve treatment outcomes for BPD. The present process-outcome pilot study aimed to examine the effects of the motive-oriented therapeutic relationship on the cognitive biases of patients with BPD. Change in biased cognitions in N=10 patients who were subject to MOTR was compared to that of N=10 patients who received psychiatric-psychodynamic treatment (Gunderson & Links, 2008). Results show a greater decrease in over-generalizations in patients who received MOTR, compared to the patients who received the psychiatric-psychodynamic treatment. These changes were related to outcome in various ways. These findings underline the importance of an individualized case formulation method in bringing about therapeutic change.

Redox dysregulation in the pathophysiology of schizophrenia and bipolar disorder: insights from animal models.

Abstract Significance: Schizophrenia (SZ) and bipolar disorder (BD) are classified as two distinct diseases. However, accumulating evidence shows that both disorders share genetic, pathological, and epidemiological characteristics. Based on genetic and functional findings, redox dysregulation due to an imbalance between pro-oxidants and antioxidant defense mechanisms has been proposed as a risk factor contributing to their pathophysiology. Recent Advances: Altered antioxidant systems and signs of increased oxidative stress are observed in peripheral tissues and brains of SZ and BD patients, including abnormal prefrontal levels of glutathione (GSH), the major cellular redox regulator and antioxidant. Here we review experimental data from rodent models demonstrating that permanent as well as transient GSH deficit results in behavioral, morphological, electrophysiological, and neurochemical alterations analogous to pathologies observed in patients. Mice with GSH deficit display increased stress reactivity, altered social behavior, impaired prepulse inhibition, and exaggerated locomotor responses to psychostimulant injection. These behavioral changes are accompanied by N-methyl-D-aspartate receptor hypofunction, elevated glutamate levels, impairment of parvalbumin GABA interneurons, abnormal neuronal synchronization, altered dopamine neurotransmission, and deficient myelination. Critical Issues: Treatment with the GSH precursor and antioxidant N-acetylcysteine normalizes some of those deficits in mice, but also improves SZ and BD symptoms when given as adjunct to antipsychotic medication. Future Directions: These data demonstrate the usefulness of GSH-deficient rodent models to identify the mechanisms by which a redox imbalance could contribute to the development of SZ and BD pathophysiologies, and to develop novel therapeutic approaches based on antioxidant and redox regulator compounds. Antioxid. Redox Signal. 18, 1428-1443.

Cannabis dependence in Swiss adolescents: An exploration of the role of anxiety, coping styles and psychosocial difficulties

This naturalistic cross-sectional study explores how and to what extent cannabis dependence was associated with intrapersonal aspects (anxiety, coping styles) and interpersonal aspects of adolescent functioning (school status, family relationships, peer relationships, social life). A convenience sample of 110 adolescents (aged 12 to 19) was recruited and subdivided into two groups (38 with a cannabis dependence and 72 nondependent) according to DSM-IV-TR criteria for cannabis dependence. Participants completed the State-Trait Anxiety Inventory (STAI-Y), the Coping Across Situations Questionnaire (CASQ), and the Adolescent Drug Abuse Diagnosis (ADAD) interview investigating psychosocial and interpersonal problems in an adolescent's life. Factors associated with cannabis dependence were explored with logistic regression analyses. The results indicated that severity of problems in social life and peer relationships (OR = 1.68, 95% CI = 1.21 - 2.33) and avoidantcoping (OR = 4.22, 95% CI = 1.01 - 17.73) were the only discriminatory factors for cannabis dependence. This model correctly classified 84.5% of the adolescents. These findings are partially consistent with the "self-medication hypothesis" and underlined the importance of peer relationships and dysfunctional coping strategies in cannabis dependence in adolescence. Limitations of the study and implications for clinical work with adolescents are discussed.

Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome.

AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel BrS SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C. The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant I(Na) was accelerated in a voltage-dependent manner and the steady-state inactivation curve was shifted by 11.6 mV towards negative potentials. No change was observed regarding activation characteristics. Altogether, these biophysical alterations decreased the availability of I(Na). In the simulations, the I(to) density necessary to precipitate repolarization differed minimally between the two genotypes. In contrast, the mutation greatly affected conduction across a structural heterogeneity and precipitated conduction block. CONCLUSION: Our data confirm that mutations of the C-terminal domain of Na(v)1.5 alter the inactivation of the channel and support the notion that conduction alterations may play a significant role in the pathogenesis of BrS.

Genome-wide association study of co-occurring anxiety in major depression.

OBJECTIVES: Co-morbidity between depression and anxiety disorders is common. In this study we define a quantitative measure of anxiety by summating four anxiety items from the SCAN interview in a large collection of major depression (MDD) cases to identify genes contributing to this complex phenotype. METHODS: A total of 1522 MDD cases dichotomised according to those with at least one anxiety item scored (n = 1080) and those without anxiety (n = 442) were analysed, and also compared to 1588 healthy controls at a genome-wide level, to identify genes that may contribute to anxiety in MDD. RESULTS: For the quantitative trait, suggestive evidence of association was detected for two SNPs, and for the dichotomous anxiety present/absent ratings for three SNPs at genome-wide level. In the genome-wide analysis of MDD cases with co-morbid anxiety and healthy controls, two SNPs attained P values of < 5 × 10⁻⁶. Analysing candidate genes, P values ≤ 0.0005 were found with three SNPs for the quantitative trait and three SNPs for the dichotomous trait. CONCLUSIONS: This study provides an initial genome-wide assessment of possible genetic contribution to anxiety in MDD. Although suggestive evidence of association was found for several SNPs, our findings suggest that there are no common variants strongly associated with anxious depression.

Role of the cannabinoid system in the effects induced by nicotine on anxiety-like behaviour in mice

Rationale: Acute behavioural effects and motivational responses induced by nicotine can be modulated by the endocannabinoid system supporting the existence of a physiological interaction between these two systems. Objectives: The present study was designed to examine the possible involvement of the cannabinoid system in the anxiolytic- and anxiogenic-like responses induced by nicotine in mice. Methods: Animals were only exposed once to nicotine. The acute administration of low (0.05, sc) or high (0.8 mg/kg, sc) doses of nicotine produced opposite effects in the elevated plus-maze, i.e., anxiolytic- and anxiogenic-like responses, respectively. The effects of the pretreatment with the CB1 cannabinoid receptor antagonist, rimonabant (0.25, 0.5 and 1 mg/kg, ip), and the cannabinoid agonist, 9-tetrahydrocannabinol (0.1 mg/kg, ip), were evaluated on the anxiolytic- and anxiogenic-like responses induced by nicotine. Results: Rimonabant completely abolished nicotine-induced anxiolytic-like effects and increased the anxiogenic-like responses of nicotine, suggesting an involvement of CB1 receptors in these behavioural responses. On the other hand, 9-tetrahydrocannabinol failed to modify nicotine anxiolytic-like responses, but attenuated its anxiogenic-like effects. In addition the association of non-effective doses of 9-tetrahydrocannabinol and nicotine produced clear anxiolytic-like responses. Conclusions: These results demonstrate that the endogenous cannabinoid system is involved in the regulation of nicotine anxiety-like behaviour in mice, and provide new findings to support the use of cannabinoid antagonists in the treatment of tobacco addiction.

Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder

Background: There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype. Methods: We analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.Results: We did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.Conclusions: Our results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.