Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls.

BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

"Efficacy of brief interdisciplinary psychotherapeutic intervention for moto conversion disorder and non-epileptic attacks"

Comparer une intervention psychothérapeutique interdisciplinaire brève à une prise en charge standard comme traitements pour des patients ayant récemment été diagnostiqués comme souffrant d'un trouble de conversion moteur sévère ou d'attaques non-épileptiques. Méthodes Cette étude randomisée contrôlée de 23 patients consécutifs a comparé a) un groupe d'intervention psychothérapeutique interdisciplinaire recevant 4-6 séances par un psychiatre de liaison, la première et dernière séance étant couplée à une consultation neurologique et à une consultation conjointe par le neurologue et le psychiatre; b) un groupe de prise en charge standard. Après l'intervention, les patients ont été évalués à 2, 6 et 12 mois par le questionnaire de dissociation somatoforme SDQ-20, l'échelle d'impression clinique globale, l'échelle de Rankin, l'utilisation des services de santé, la santé mentale en général (MADRS, échelle de dépression de Beck, composante de santé mentale du SF-36), la qualité de vie (SF-36). Nous avons calculé des modèles linéaires mixtes. Résultats Notre intervention a mené à une amélioration statistiquement significative ? des symptômes physiques (par une mesure du SDQ-20 (p<0.02), et par l'échelle de l'impression clinique globale (p=0.02)) ? des symptômes psychologiques (meilleurs scores à la composante de santé mentale du SF-36 (p<0.05) et à l'inventaire de dépression de Beck (p<0.05)) ? et à une réduction des nouvelles hospitalisations après l'intervention (p<0.05). Conclusion Une intervention psychothérapeutique interdisciplinaire brève en étroite collaboration avec des spécialistes en neurologie dans un cadre de psychiatrie de consultation et liaison a un effet statistiquement significatif sur l'amélioration de patients souffrant de trouble de conversion moteur et d'attaques non-épileptiques.

The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders.

BACKGROUND: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. METHODS: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. RESULTS: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LIMITATIONS: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. CONCLUSIONS: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

A mild form of SLC29A3 disorder: a frameshift deletion leads to the paradoxical translation of an otherwise noncoding mRNA splice variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the"rescue" role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic.

NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina.

We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting, dehydration, and elevated transaminases. They had frequent infections, hypogammaglobulinemia, reduced natural killer cells, and the Pelger-Huët anomaly of their granulocytes. Their facial features were similar with a pointed chin and proptosis; loose skin and reduced subcutaneous fat gave them a progeroid appearance. Skeletal features included short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, and small C1-C2 vertebrae causing cervical instability and myelopathy. Retinal dystrophy and optic atrophy were present in one patient. NBAS is a component of the synthaxin-18 complex and is involved in nonsense-mediated mRNA decay control. Putative loss-of-function mutations in NBAS are already known to cause disease in humans. A specific founder mutation has been associated with short stature, optic nerve atrophy and Pelger-Huët anomaly of granulocytes (SOPH) in the Siberian Yakut population. A more recent report associates NBAS mutations with recurrent acute liver failure in infancy in a group of patients of European descent. Our observations indicate that the phenotypic spectrum of NBAS deficiency is wider than previously known and includes skeletal, hepatic, metabolic, and immunologic aspects. Early recognition of the skeletal phenotype is important for preventive management of cervical instability. © 2015 Wiley Periodicals, Inc.

Sex ratio bias, male aggression, and population collapse in lizards.

The adult sex ratio (ASR) is a key parameter of the demography of human and other animal populations, yet the causes of variation in ASR, how individuals respond to this variation, and how their response feeds back into population dynamics remain poorly understood. A prevalent hypothesis is that ASR is regulated by intrasexual competition, which would cause more mortality or emigration in the sex of increasing frequency. Our experimental manipulation of populations of the common lizard (Lacerta vivipara) shows the opposite effect. Male mortality and emigration are not higher under male-biased ASR. Rather, an excess of adult males begets aggression toward adult females, whose survival and fecundity drop, along with their emigration rate. The ensuing prediction that adult male skew should be amplified and total population size should decline is supported by long-term data. Numerical projections show that this amplifying effect causes a major risk of population extinction. In general, such an "evolutionary trap" toward extinction threatens populations in which there is a substantial mating cost for females, and environmental changes or management practices skew the ASR toward males.

Video Gaming Disorder and Sport and Exercise in Emerging Adulthood: A Longitudinal Study.

Among the negative consequences of video gaming disorder, decreased participation in sport and exercise has received little attention. This study aimed to assess the longitudinal association between video gaming disorder and the level of sport and exercise in emerging adult men. A questionnaire was completed at baseline and 15-month follow-up by a representative national sample of 4,933 respondents. The seven items of the Game Addiction Scale were used to construct a latent variable representing video gaming disorder. Level of sport and exercise was also self-reported. Cross-lagged path modeling indicated a reciprocal causality between video gaming disorder and the level of sport and exercise, even after adjusting for a large set of confounders. These findings support the need for better promotion of sport and exercise among emerging adults in order to contribute to the prevention of video gaming disorder, and to raise the level of sport and exercise activity in addicted gamers.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Independent and combined associations of risky single-occasion drinking and drinking volume with alcohol use disorder: Evidence from a sample of young Swiss men.

BACKGROUND: Risky single-occasion drinking (RSOD) is a prevalent and potentially harmful alcohol use pattern associated with increased alcohol use disorder (AUD). However, RSOD is commonly associated with a higher level of alcohol intake, and most studies have not controlled for drinking volume (DV). Thus, it is unclear whether the findings provide information about RSOD or DV. This study sought to investigate the independent and combined effects of RSOD and DV on AUD. METHODS: Data were collected in the longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) among 5598 young Swiss male alcohol users in their early twenties. Assessment included DV, RSOD, and AUD at two time points. Generalized linear models for binomial distributions provided evidence regarding associations of DV, RSOD, and their interaction. RESULTS: DV, RSOD, and their interaction were significantly related to the number of AUD criteria. The slope of the interaction was steeper for non/rare RSOD than for frequent RSOD. CONCLUSIONS: RSOD appears to be a harmful pattern of drinking, associated with increased AUD and it moderated the relationship between DV and AUD. This study highlighted the importance of taking drinking patterns into account, for both research and public health planning, since RSO drinkers constitute a vulnerable subgroup for AUD.

Colony-colony interactions between highly invasive ants

Among invasive species, ants are a particularly prominent group with enormous impacts on native biodiversity and ecosystem functioning. Globalization and on-going climate change are likely to increase the rate of ant invasions in the future, leading to simultaneous introductions of several highly invasive species within the same area, Here, we investigate pairwise interactions among four highly invasive species, Linepithema humile,Lashis neglectus, Pheidole megacephala and Wasmannia auropunctata, at the whole colony level, using a laboratory set-up. :Each colony consisted of 300 workers and one queen. The number of surviving workers in the competing colonies was recorded daily over 7 weeks. We modelled the survival of each colony during pairwise colony interactions, using a nonlinear model characterizing the survival dynamics of each colony individually. The least dominant species was P. megacephala, which always went extinct. Interactions among the three other species showed more complex dynamics, rendering the outcome of the interactions less predictable. Overall, W auropunctata and L neglectus were the most dominant species. This study shows the importance of scaling up to the colony level in order to gain realism in predicting the outcome of multiple invasions.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Azorin JM, Bowden CL, Garay RP, Perugi G, Vieta E, Young AH. Source Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France. Abstract About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence.