Associations between genetic liabilities to smoking behavior and schizophrenia symptoms in patients with a psychotic disorder, their siblings and healthy controls.

It is unknown how smoking behavior polygenic scores (PRS) relate to psychosis and psychotic symptoms. To elucidate this, genotype and phenotype data were collected from patients with schizophrenia, their unaffected siblings, and healthy controls in a six-year follow-up prospective cohort study. Associations between smoking behaviors, PRS and schizophrenia symptoms were explored using linear mixed-effect models. The mean number of cigarettes smoked per day were 18 for patients, 13 for siblings and 12 for controls. In the overall sample, PRSs-smoking initiation (i.e., ever smoking as a binary phenotype, PRS-SI) were positively associated with positive symptoms, negative symptoms, and depressive symptoms, whereas PRSs-AI (age at regular smoking initiation) were negatively associated with all symptom dimensions, with similar effect sizes. When considering groups separately, PRS were only associated with psychotic symptoms in siblings and controls. In conclusion, unaffected siblings show smoking behaviors at an intermediate level between patients and healthy controls. Additionally, PRS-SI and PRS-AI are associated with all symptom dimensions only in unaffected siblings and healthy controls, possibly owing to the dominant role of other (genetic) risk factors in patients. Future studies may examine mechanisms via which genetic risk for smoking affects mental health symptoms.

[Disruptive behaviour problems in childhood: studies on phenotypic heterogeneity and neurobiology from the Generation R Study]. / Disruptieve gedragsproblemen op de kinderleeftijd: studies naar fenotypische heterogeniteit en neurobiologie in de Generation R Studie.

BACKGROUND: Disruptive behaviour problems in childhood are strongly predictive of physical and mental health problems and criminality. A better understanding of the development of children with disruptive behaviour problems will help improve our understanding of later severe mental illnesses.
AIM: To gain insights into the neurodevelopment of children with disruptive behaviour problems. Here, we focused on their phenotypic heterogeneity and the underlying neurobiological substrates of disruptive behaviour problems.
METHOD: All studies described in the discussed thesis were embedded in the Generation R Study, a prospective population-based birth cohort from Rotterdam, the Netherlands. Data were, amongst others, collected through multi-informant questionnaires and neuroimaging.
RESULTS: Empirically obtained dimensions of disruptive behaviour problems included oppositional/disobedient behaviour, physical aggression, irritability, and delinquent behaviour. Less white matter microstructure was related to more delinquent behaviour, taking into account the multi-dimensionality of disruptive behaviour problems. Callous traits were characterised by widespread macro- and microstructural differences across the brain.
CONCLUSION: These studies have shown that disruptive behaviour problems in childhood can be best conceptualized as a complex multi-dimensional phenotype. Taking into account this multi-dimensional heterogeneity has proven beneficial for the finding of underlying neurobiological mechanisms. Considering disruptive behaviour problems are predictive of later severe mental disorders, it is paramount to acknowledge the neurodevelopmental perspective on behaviour problems.

Correction to: Implementing a hospital-wide protocol for Staphylococcus aureus bacteremia.

The article "Implementing a hospital-wide protocol for Staphylococcus aureus bacteremia", written by K. Bolhuis, L. J. Bakker, J. T. Keijer, and P. J. de Vries was originally published electronically on 31 May 2018 with incorrect copyright line in the publisher's internet portal.

Implementing a hospital-wide protocol for Staphylococcus aureus bacteremia.

Staphylococcus aureus bacteraemia (SAB) is associated with high-mortality and complication rates. A multidisciplinary approach is needed to predict, detect and treat complications. In this pre- and post-intervention study, we investigated the effects of a hospital-wide protocol for diagnosis, classification and treatment of SAB. It was hypothesized that complications and endocarditis would be better identified and treated. Medical records of SAB patients admitted in 2011 and 2012 (pre) were analysed. In 2013, a protocol, describing risk factors, diagnostic classification and recommended treatment, was implemented. In 2014 and 2015 (post), SAB patients were followed prospectively. Transthoracic (TTE) or transoesophageal cardiac ultrasound (TEE) was chosen following a decision tree. A resident internal medicine acted as contact person. Pre-intervention, 98 patients were eligible for analysis compared to 85 patients post-intervention. Age and number of risk factors were slightly higher post-intervention; other baseline characteristics were similar. Most SAB-patients were classified as complicated (89 and 82% pre- and post-intervention, respectively). Follow-up blood cultures drawn within 2 days after initiating treatment increased from 51 to 85%. Cardiac ultrasounds increased from 44 to 83% for TTE and 13 to 24% for TEE. Endocarditis was more frequently diagnosed (4 vs. 12%). Additionally, duration of antibiotic therapy increased. The 3-month mortality did not change significantly (33% pre-intervention vs. 35% post-intervention; p > 0.05). Introduction of a hospital-wide protocol for SAB management increased standard of care, created awareness among clinicians to properly classify SAB, search for endocarditis and adapt duration of antibiotic treatment. Mortality did not decrease.

Psychotic-like experiences in pre-adolescence: what precedes the antecedent symptoms of severe mental illness?

OBJECTIVE: Adolescent psychotic-like experiences predict the onset of psychosis, but also predict subsequent non-psychotic disorders. Therefore, it is crucial to better understand the aetiology of psychotic-like experiences. This study examined whether (a) child emotional and behavioural problems at 3 and 6 years, or (b) childhood adversities were associated with psychotic-like experiences at age 10 years. METHOD: This prospective study was embedded in the Generation R Study; 3984 children (mean age 10 years) completed a psychotic-like experiences questionnaire. Mothers reported problems of their child at ages 3, 6 and 10 years. Additionally, mothers were interviewed about their child's adversities. RESULTS: Psychotic-like experiences were endorsed by ~20% of children and predicted by both emotional and behavioural problems at 3 years (e.g. emotional-reactive problems: ORadjusted = 1.10, 95% CI: 1.06-1.15, aggressive behaviour: ORadjusted = 1.03, 95% CI: 1.02-1.05) and 6 years (e.g. anxious/depressed problems: ORadjusted = 1.11, 95% CI: 1.06-1.15, aggressive behaviour: ORadjusted = 1.04, 95% CI: 1.04-1.05). Childhood adversities were associated with psychotic-like experiences (>2 adversities: ORadjusted = 2.24, 95% CI: 1.72-2.92), which remained significant after adjustment for comorbid psychiatric problems. CONCLUSION: This study demonstrated associations between early adversities, childhood emotional and behavioural problems and pre-adolescent psychotic-like experiences, which will improve the understanding of children at increased risk of severe mental illness.

Aetiological overlap between obsessive-compulsive and depressive symptoms: a longitudinal twin study in adolescents and adults.

BACKGROUND: Depression is commonly co-morbid with obsessive-compulsive disorder (OCD). However, it is unknown whether depression is a functional consequence of OCD or whether these disorders share a common genetic aetiology. This longitudinal twin study compared these two hypotheses. METHOD: Data were drawn from a longitudinal sample of adolescent twins and siblings (n = 2651; Genesis 12-19 study) and from a cross-sectional sample of adult twins (n = 4920). The longitudinal phenotypic associations between OCD symptoms (OCS) and depressive symptoms were examined using a cross-lag model. Multivariate twin analyses were performed to explore the genetic and environmental contributions to the cross-sectional and longitudinal relationship between OCS and depressive symptoms. RESULTS: In the longitudinal phenotypic analyses, OCS at time 1 (wave 2 of the Genesis 12-19 study) predicted depressive symptoms at time 2 (wave 3 of the Genesis 12-19 study) to a similar extent to which depressive symptoms at time 1 predicted OCS at time 2. Cross-sectional twin analyses in both samples indicated that common genetic factors explained 52-65% of the phenotypic correlation between OCS and depressive symptoms. The proportion of the phenotypic correlation due to common non-shared environmental factors was considerably smaller (35%). In the adolescent sample, the longitudinal association between OCS at time 1 and subsequent depressive symptoms was accounted for by the genetic association between OCS and depressive symptoms at time 1. There was no significant environmental association between OCS and later depressive symptoms. CONCLUSIONS: The present findings show that OCS and depressive symptoms co-occur primarily due to shared genetic factors and suggest that genetic, rather than environmental, effects account for the longitudinal relationship between OCS and depressive symptoms.