Genetic overlap and causal associations between smoking behaviours and mental health

Cigarette smoking is a modifiable behaviour associated with mental health. We investigated the degree of genetic overlap between smoking behaviours and psychiatric traits and disorders, and whether genetic associations exist beyond genetic influences shared with confounding variables (cannabis and alcohol use, risk-taking and insomnia). Second, we investigated the presence of causal associations between smoking initiation and psychiatric traits and disorders. We found significant genetic correlations between smoking and psychiatric disorders and adult psychotic experiences. When genetic influences on known covariates were controlled for, genetic associations between most smoking behaviours and schizophrenia and depression endured (but not with bipolar disorder or most psychotic experiences). Mendelian randomization results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences, although not consistently across all sensitivity analyses. In conclusion, smoking and psychiatric disorders share genetic influences that cannot be attributed to covariates such as risk-taking, insomnia or other substance use. As such, there may be some common genetic pathways underlying smoking and psychiatric disorders. In addition, smoking may play a causal role in vulnerability for mental illness

Rate of information processing and reaction time of aircraft pilots and non-pilots.

Reaction time and rate of information processing are cited as critical components in the make-up of pilots. A need was identified to establish the validity of various chronometric measures in the selection of pilots. Fifty-eight military and commercial pilots and twenty non-pilots were subjected to Schepers’ Computerised Information Processing Test Battery, which measures reaction time, form discrimination time, colour discrimination time, rate of information processing(perceptual) and rate of information processing (conceptual). Five hypotheses and one postulate were formulated and tested. The results indicate that pilots could be differentiated from non-pilots with 92,3% accuracy. However, the results need to be cross-validated before they are used for selection

Understanding the relationship between loneliness, substance use traits and psychiatric disorders: A genetically informed approach

Loneliness is a common, yet distressing experience associated with adverse outcomes including substance use problems and psychiatric disorders. To what extent these associations reflect genetic correlations and causal relationships is currently unclear. We applied Genomic Structural Equation Modelling (GSEM) to dissect the genetic architecture between loneliness and psychiatric-behavioural traits. Included were summary statistics from 12 genome-wide association analyses, including loneliness and 11 psychiatric phenotypes (range N: 9,537 – 807,553). We first modelled latent genetic factors amongst the psychiatric traits to then investigate potential causal effects between loneliness and the identified latent factors, using multivariate genome-wide association analyses and bidirectional Mendelian randomization. We identified three latent genetic factors, encompassing neurodevelopmental/mood conditions, substance use traits and disorders with psychotic features. GSEM provided evidence of a unique association between loneliness and the neurodevelopmental/mood conditions latent factor. Mendelian randomization results were suggestive of bidirectional causal effects between loneliness and the neurodevelopmental/mood conditions factor. These results imply that a genetic predisposition to loneliness may elevate the risk of neurodevelopmental/mood conditions, and vice versa. However, results may reflect the difficulty of distiguishing between loneliness and neurodevelopmental/mood conditions, which present in similar ways. We suggest, overall, the importance of addressing loneliness in mental health prevention and policy

Genetic overlap and causal associations between smoking behaviours and mental health

Cigarette smoking is a modifiable behaviour associated with mental health. We investigated the degree of genetic overlap between smoking behaviours and psychiatric traits and disorders, and whether genetic associations exist beyond genetic influences shared with confounding variables (cannabis and alcohol use, risk-taking and insomnia). Second, we investigated the presence of causal associations between smoking initiation and psychiatric traits and disorders. We found significant genetic correlations between smoking and psychiatric disorders and adult psychotic experiences. When genetic influences on known covariates were controlled for, genetic associations between most smoking behaviours and schizophrenia and depression endured (but not with bipolar disorder or most psychotic experiences). Mendelian randomization results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences, although not consistently across all sensitivity analyses. In conclusion, smoking and psychiatric disorders share genetic influences that cannot be attributed to covariates such as risk-taking, insomnia or other substance use. As such, there may be some common genetic pathways underlying smoking and psychiatric disorders. In addition, smoking may play a causal role in vulnerability for mental illness

A twin study on the association between psychotic experiences and tobacco use during adolescence

Objective: Psychotic experiences (PE) are dimensional phenomena in the general population that resemble psychotic symptoms, such as paranoia and hallucinations. This is the first twin study to explore the degree to which tobacco use and PE share genetic or environme ntal influences. Previous studies on the association between adolescent tobacco use and PE have not considered PE dimensionally, included negative symptoms, or accounted for confounding by sleep disturbance and stressful life events . Method: An unselecte d adolescent twin sample (N=3787 pairs; M age=16.16 years) reported on PE (paranoia, hallucinations, cognitive disorganization, grandiosity and anhedonia) and regularity of tobacco use. Parents rated the twins’ negative symptoms. Regression analyses were c onducted while adjusted for sociodemographic characteristics, prenatal maternal smoking, cannabis use, sleep disturbance, and stressful life events. Bivariate twin modelling was employed to estimate the degree of genetic and common and unique environmental influences shared between tobacco use and PE. Results: Regular smokers were significantly more likely to experience paranoia, hallucinations, cognitive disorganization and negative symptoms ( E =.17 - .34), but not grandiosity or anhedonia, than non - smokers, after adjustment for confounders. Paranoia, hallucinations and cognitive disorganization correlated ≥ .15 with tobacco use ( r = .15 - .21, all p<.001). Significant genetic correlations (r A =.37 - .45) were found. Genetic influences accounted for most of the ass ociation between tobacco use and paranoia (84%) and cognitive disorganization (81%). Familial influences accounted for 80% of the association between tobacco use and hallucinations. Conclusion: Tobacco use and PE during adolescence were associated after ad justment for confounders. They appear to co - occur largely due to shared genetic influences. Lay summary: Individual psychotic experiences, such as paranoid thoughts and having hallucinations, were assessed in this study as dimensional phenomena in the comm unity in mid - adolescence, alongside tobacco use. The classic twin design including identical and fraternal twins was employed, with a sample of approximately 3700 twin pairs in mid - adolescence. Regular tobacco use was found to be associated with psychotic experiences during adolescence even after taking account possible confounds such as social background, cannabis use, maternal smoking during pregnancy, sleeping habits and stressful life events. S ome the same genetic influences were found to underlie adolescent smoking and individual psychotic experiences, specifically paranoia, hallucinations and cognitive disorganization

Clinical Implications of Epigenetic Dysregulation in Perinatal Hypoxic-Ischemic Brain Damage

Placental and fetal hypoxia caused by perinatal hypoxic-ischemic events are major causes of stillbirth, neonatal morbidity, and long-term neurological sequelae among surviving neonates. Brain hypoxia and associated pathological processes such as excitotoxicity, apoptosis, necrosis, and inflammation, are associated with lasting disruptions in epigenetic control of gene expression contributing to neurological dysfunction. Recent studies have pointed to DNA (de)methylation, histone modifications, and non-coding RNAs as crucial components of hypoxic-ischemic encephalopathy (HIE). The understanding of epigenetic dysregulation in HIE is essential in the development of new clinical interventions for perinatal HIE. Here, we summarize our current understanding of epigenetic mechanisms underlying the molecular pathology of HI brain damage and its clinical implications in terms of new diagnostic, prognostic, and therapeutic tools.Fil: Bustelo, Martí. Universidad de Buenos Aires; Argentina. Maastricht University Medical Center; Países Bajos. Universidad Católica de Cuyo - Sede San Juan; ArgentinaFil: Barkhuizen, Melinda. Maastricht University Medical Center; Países BajosFil: van den Hove, Daniel L. A.. Universiteit Maastricht.; Países BajosFil: Steinbusch, Harry Wilhelm. M.. Universiteit Maastricht.; Países BajosFil: Bruno, Martin. Universidad Católica de Cuyo - Sede San Juan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Loidl, Cesar Fabian. Universidad Catolica de Cuyo - Sede San Luis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Gavilanes, Antonio W. Danilo. Maastricht University Medical Cente; Países Bajo

Rapid, progressive neuropathic arthropathy of the hip in a patient co-infected with human immunodeficiency virus, hepatitis C virus and tertiary syphilis: case report

BACKGROUND: Syphilis is a chronic infection that is classified into three stages. In its tertiary stage, syphilis spreads to the brain, heart and other organs; the lesions may involve the skin, mucous membranes and bones. Neuropathic arthropathy associated with tertiary syphilis has rarely been described in Europe and its association with HIV-HCV co-infection has not been reported so far.This article reports the case of a man with tertiary syphilis presenting with rapidly evolving neuropathic arthropathy of the hip and extensive bone destruction. CASE PRESENTATION: On initial presentation, the patient complained of progressively worsening left-sided coxalgia without localized or generalized inflammation. The patient reported to have no history of previous infections, trauma or cancer. Plain x-ray films of the left coxofemoral joint showed marked degeneration with necrosis of the proximal epiphysis of femur and morphological alterations of the acetabulum without protrusion. Primary coxarthrosis was diagnosed and hip arthroplasty was offered, but the patient declined treatment. Three months later, the patient presented a marked deterioration of his general condition. He disclosed that he was seropositive for HCV and HIV, as confirmed by serology. Syphilis serology testing was also positive. A Girdlestone's procedure was performed and samples were collected for routine cultures for bacteria and acid fast bacilli, all resulting negative.Although histological findings were inconclusive, confirmed positive serology for syphilis associated with progressive arthropathy was strongly suggestive of tertiary syphilis, probably exacerbated by HIV-HCV co-infection. The patient partially recovered the ability to walk. CONCLUSIONS: Due to the resurgence of syphilis, this disease should be considered as a possible cause of neuropathic arthropathy when other infectious causes have been ruled out, particularly in patients with HIV and/or HCV co-infection

Language and learning science in South Africa

South Africa is a multilingual country with 11 official languages. However, English dominates as the language of access and power and although the Language-in- Education Policy (1997) recommends school language policies that will promote additive bilingualism and the use of learners' home languages as languages of learning and teaching, there has been little implementation of these recommendations by schools. This is despite the fact that the majority of learners do not have the necessary English language proficiency to successfully engage with the curriculum and that teachers frequently are obliged to resort to using the learners' home language to mediate understanding. This research investigates the classroom language practices of six Grade 8 science teachers, teaching science through the medium of English where they and their learners share a common home language, Xhosa. Teachers' lessons were videotaped, transcribed and analysed for the opportunities they offered learners for language development and conceptual challenge. The purpose of the research is to better understand the teachers' perceptions and problems and to be able to draw on examples of good practice, to inform teacher training and to develop a coherent bilingual approach for teaching science through the medium of English as an additional language

NK-, NKT-and CD8-derived IFNγ drives myeloid cell activation and erythrophagocytosis, resulting in Trypanosomosis-associated acute anemia

African trypanosomes are the causative agents of Human African Trypanosomosis (HAT/Sleeping Sickness) and Animal African Trypanosomosis (AAT/Nagana). A common hallmark of African trypanosome infections is inflammation. In murine trypanosomosis, the onset of inflammation occurs rapidly after infection and is manifested by an influx of myeloid cells in both liver and spleen, accompanied by a burst of serum pro-inflammatory cytokines. Within 48 hours after reaching peak parasitemia, acute anemia develops and the percentage of red blood cells drops by 50%. Using a newly developed in vivo erythrophagocytosis assay, we recently demonstrated that activated cells of the myeloid phagocytic system display enhanced erythrophagocytosis causing acute anemia. Here, we aimed to elucidate the mechanism and immune pathway behind this phenomenon in a murine model for trypanosomosis. Results indicate that IFNγ plays a crucial role in the recruitment and activation of erythrophagocytic myeloid cells, as mice lacking the IFNγ receptor were partially protected against trypanosomosis-associated inflammation and acute anemia. NK and NKT cells were the earliest source of IFNγ during T. b. brucei infection. Later in infection, CD8+ and to a lesser extent CD4+ T cells become the main IFNγ producers. Cell depletion and transfer experiments indicated that during infection the absence of NK, NKT and CD8+ T cells, but not CD4+ T cells, resulted in a reduced anemic phenotype similar to trypanosome infected IFNγR-/- mice. Collectively, this study shows that NK, NKT and CD8+ T cell-derived IFNγ is a critical mediator in trypanosomosis-associated pathology, driving enhanced erythrophagocytosis by myeloid phagocytic cells and the induction of acute inflammation-associated anemia