Comparing cognition in parents with schizophrenia or bipolar disorder and their 7-year-old offspring.

Individuals with schizophrenia (SZ) or bipolar disorder (BP) display cognitive impairments, while their first-degree relatives perform at an intermediate level between the patient groups and controls. However, the environmental impact of having an ill relative likely varies with the type of kinship and some studies suggest that offspring may be particularly disadvantaged. The present study aimed to investigate the relationship between parent and child cognition in parents with SZ or BD and their 7-year-old offspring. A population-based cohort of 522 children (parental SZ, n = 202; parental BP, n = 120; controls, n = 200) and their parents underwent the same assessment battery covering a wide range of cognitive functions. We used Bayesian statistics to model performance. We found that performance on non-verbal tests was better in offspring than parents with SZ or BP, using the controls as reference. However, for verbal tests, there was little to no evidence for this pattern or even some evidence for the opposite in the BP group: relatively better performance in parents than offspring. The findings suggest that the offspring of parents with SZ or BP may be particularly disadvantaged in verbal abilities. Future studies will show whether this pattern persists throughout development.

Aripiprazole dose associations with metabolic adverse effect: Results from a longitudinal study.

OBJECTIVE: Weight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure. METHODS: 422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models. RESULTS: Aripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: -0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025). CONCLUSION: Aripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred.

Associations of Valproate Doses With Weight Gain in Adult Psychiatric Patients: A 1-Year Prospective Cohort Study.

Objective: The aim of this study was to evaluate valproate dose association with weight change, blood glucose, lipid levels, and blood pressure in a psychiatric population.Methods: Data from 215 patients taking valproate for up to 1 year were collected from 2 longitudinal studies that monitored metabolic variables between 2007 and 2022. Linear mixed-effect models and logistic regressions were used to analyze the associations between valproate doses and metabolic outcomes.Results: An increase in valproate dose of 500 mg was associated with a weight change of +0.52% per month over a year (P < .001). The association between valproate dose and weight change was evident both before and after 3 months of treatment. Weight increase was greater for treatment durations of < 3 months compared to ≥ 3 months (+0.56%, P < .001 and +0.12%, P = .02 per month, respectively). Using piecewise regression, a significant association between dose and weight gain was observed in patients receiving doses equal to or above the median dose (1,300 mg/d), with a +0.50% increase in weight for each dose increment of 500 mg (P = .004). Among men, each 500 mg dose increment was associated with weight increases of +0.59% per month (P = .004), whereas a trend was observed for women (+0.40%, P = .09). No associations were found between valproate doses and blood glucose, lipid levels, or blood pressure over a 6-month treatment period.Conclusions: This study provides evidence that valproate dose, mainly for doses at or above 1,300 mg/d, is associated with weight gain in psychiatric patients, suggesting that the lowest effective doses should be prescribed to minimize weight gain.

Objectively assessed sleep and physical activity in depression subtypes and its mediating role in their association with cardiovascular risk factors.

The aims of this study were to investigate the associations of major depressive disorder (MDD) and its subtypes (atypical, melancholic, combined, unspecified) with actigraphy-derived measures of sleep, physical activity and circadian rhythms; and test the potentially mediating role of sleep, physical activity and circadian rhythms in the well-established associations of the atypical MDD subtype with Body Mass Index (BMI) and the metabolic syndrome (MeS). The sample consisted of 2317 participants recruited from an urban area, who underwent comprehensive somatic and psychiatric evaluations. MDD and its subtypes were assessed via semi-structured diagnostic interviews. Sleep, physical activity and circadian rhythms were measured using actigraphy. MDD and its subtypes were associated with several actigraphy-derived variables, including later sleep midpoint, low physical activity, low inter-daily stability and larger intra-individual variability of sleep duration and relative amplitude. Sleep midpoint and physical activity fulfilled criteria for partial mediation of the association between atypical MDD and BMI, and physical activity also for partial mediation of the association between atypical MDD and MeS. Our findings confirm associations of MDD and its atypical subtype with sleep and physical activity, which are likely to partially mediate the associations of atypical MDD with BMI and MeS, although most of these associations are not explained by sleep and activity variables. This highlights the need to consider atypical MDD, sleep and sedentary behavior as cardiovascular risk factors.

Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome.

BACKGROUND: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. METHODS: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. RESULTS: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. CONCLUSIONS: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.

Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Affective lability in parents with schizophrenia or bipolar disorder and their co-parents - The Danish High Risk and Resilience Study VIA 7.

In bipolar disorder, dysregulation of affect is a core feature while knowledge on affective lability in schizophrenia is sparse. Research on affective lability in partners to individuals with schizophrenia or bipolar disorder is also lacking. The objective of this study was to investigate affective lability in parents with schizophrenia or bipolar disorder, and their co-parents without these disorders. The Danish High Risk and Resilience Study - VIA 7 is a population-based cohort study. This study focuses on parents diagnosed with schizophrenia (n = 148), their co-parents (n = 157), parents with bipolar disorder (n = 98), their co-parents (n = 89) and control parents (n = 359). The Affective Lability Scale - short form (ALS-SF) was used to measure affective lability. We found significantly higher levels of affective lability in parents with schizophrenia and bipolar disorder compared with controls, but no significant differences between bipolar disorder and schizophrenia. Co-parents to parents with schizophrenia had significantly higher levels of affective lability compared to controls. Our results add to the existing knowledge concerning underlying transdiagnostic factors and nonrandom mating in schizophrenia and bipolar disorder and highlight the need for studies of parental affective lability as a potential risk factor for offspring in families with parental schizophrenia or bipolar disorder.

A family-based study of genetic and epigenetic effects across multiple neurocognitive, motor, social-cognitive and social-behavioral functions.

Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case-control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways.

Association Between Early Risk Factors and Level of Functioning at Age Seven in Children at Familial Risk for Schizophrenia Or Bipolar Disorder - the Danish High Risk and Resilience Study VIA 7.

Background: Facing multiple risk factors, relative to single risk factor exposure early in life can have great implications for negative child development. Objective: We aim to examine whether the prevalence of early risk factors is higher among children with familial high risk for schizophrenia or bipolar disorder compared to controls. Further, to investigate the association between number of early risk factors and level of functioning at age seven, and whether this possible association is different in children with familial high risk compared to controls. Method: The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study of children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) and controls (N = 200). We conducted a semi-structured anamnestic interview with the child's primary caregiver to assess early risk factors from pregnancy to age four. We used the Children's Global Assessment Scale to measure level of functioning at age seven. Results: 13 out of 17 risk factors were more prevalent in children at familial high risk for schizophrenia and 7 out of 17 risk factors were more prevalent in children at familial high risk for bipolar disorder compared to controls. Level of functioning decreased 2.7 (95% CI, 2.2; 3.3)-points per risk factor, but the association was not significantly different across the three groups (p = 0.09). Conclusions: Our results showed that children at age seven with familial high risk for schizophrenia or bipolar disorder experience a greater number of early risk factors. A higher number of early risk factors were associated with lower level of functioning at age seven. However, the association is not different for children with familial high risk or controls.

The psychosis metabolic risk calculator (PsyMetRiC) for young people with psychosis: International external validation and site-specific recalibration in two independent European samples.

Background: Cardiometabolic dysfunction is common in young people with psychosis. Recently, the Psychosis Metabolic Risk Calculator (PsyMetRiC) was developed and externally validated in the UK, predicting up-to six-year risk of metabolic syndrome (MetS) from routinely collected data. The full-model includes age, sex, ethnicity, body-mass index, smoking status, prescription of metabolically-active antipsychotic medication, high-density lipoprotein, and triglyceride concentrations; the partial-model excludes biochemical predictors. Methods: To move toward a future internationally-useful tool, we externally validated PsyMetRiC in two independent European samples. We used data from the PsyMetab (Lausanne, Switzerland) and PAFIP (Cantabria, Spain) cohorts, including participants aged 16-35y without MetS at baseline who had 1-6y follow-up. Predictive performance was assessed primarily via discrimination (C-statistic), calibration (calibration plots), and decision curve analysis. Site-specific recalibration was considered. Findings: We included 1024 participants (PsyMetab n=558, male=62%, outcome prevalence=19%, mean follow-up=2.48y; PAFIP n=466, male=65%, outcome prevalence=14%, mean follow-up=2.59y). Discrimination was better in the full- compared with partial-model (PsyMetab=full-model C=0.73, 95% C.I., 0.68-0.79, partial-model C=0.68, 95% C.I., 0.62-0.74; PAFIP=full-model C=0.72, 95% C.I., 0.66-0.78; partial-model C=0.66, 95% C.I., 0.60-0.71). As expected, calibration plots revealed varying degrees of miscalibration, which recovered following site-specific recalibration. PsyMetRiC showed net benefit in both new cohorts, more so after recalibration. Interpretation: The study provides evidence of PsyMetRiC's generalizability in Western Europe, although further local and international validation studies are required. In future, PsyMetRiC could help clinicians internationally to identify young people with psychosis who are at higher cardiometabolic risk, so interventions can be directed effectively to reduce long-term morbidity and mortality. Funding: NIHR Cambridge Biomedical Research Centre (BRC-1215-20014); The Wellcome Trust (201486/Z/16/Z); Swiss National Research Foundation (320030-120686, 324730- 144064, and 320030-173211); The Carlos III Health Institute (CM20/00015, FIS00/3095, PI020499, PI050427, and PI060507); IDIVAL (INT/A21/10 and INT/A20/04); The Andalusian Regional Government (A1-0055-2020 and A1-0005-2021); SENY Fundacion Research (2005-0308007); Fundacion Marques de Valdecilla (A/02/07, API07/011); Ministry of Economy and Competitiveness and the European Fund for Regional Development (SAF2016-76046-R and SAF2013-46292-R).For the Spanish and French translation of the abstract see Supplementary Materials section.

Transmission of intelligence, working memory, and processing speed from parents to their seven-year-old offspring is function specific in families with schizophrenia or bipolar disorder.

BACKGROUND: Prior studies have shown high heritability estimates regarding within-function transmission of neurocognition, both in healthy families and in families with schizophrenia but it remains an open question whether transmission from parents to offspring is function specific and whether the pattern is the same in healthy families and families with schizophrenia or bipolar disorder. We aimed to characterize the transmission of intelligence, processing speed, and verbal working memory functions from both biological parents to their 7-year-old offspring in families with parental schizophrenia, bipolar disorder, and population-based control parents. METHODS: The population-based cohort consists of 7-year-old children with one parent diagnosed with schizophrenia (n = 186), bipolar disorder (n = 114), and of parents without schizophrenia or bipolar disorder (n = 192). Children and both parents were assessed using identical, age-relevant neurocognitive tests of intelligence, verbal working memory, and processing speed. RESULTS: In multiple regression analyses children's intelligence, verbal working memory, and processing speed scores were significantly associated with the corresponding parental cognitive function score. All associations from parents to offspring across functions were non-significant. No significant parental cognitive function by group interaction was observed. CONCLUSION: Transmissions of intelligence, processing speed, and verbal working memory from parents to offspring are function specific. The structure of transmission is comparable between families with schizophrenia, families with bipolar disorder and families without these disorders.

Associations between parental socioeconomic-, family-, and sibling status and risk of eating disorders in offspring in a Danish national female cohort.

OBJECTIVE: Studies on parental socioeconomic status (SES) and family risk factors for eating disorders (EDs) have yielded inconsistent results; however, several studies have identified high parental educational attainment as a risk factor. The aim was to evaluate associations of parental SES and family composition with anorexia nervosa (AN), bulimia nervosa (BN), and eating disorders not otherwise specified (EDNOS) in the offspring, adjusting for parental age and parental mental health. METHODS: The cohort included women born in Denmark between January 1, 1989 and December 31, 2010, derived from Danish national registers. Each person was followed from their sixth birthday until onset of the disorder of interest or to December 31, 2016. Exposure variables were: childhood SES, defined as individually evaluated parental level of income, occupation, and education; sibling status; and family composition. Outcomes were: AN, BN, EDNOS, and major depressive disorder (MDD), included as a psychiatric comparison disorder. Risks were estimated using Cox proportional hazards. RESULTS: High parental SES was associated with increased risk of especially AN, and less so BN and EDNOS, in offspring. In comparison, low SES was associated with a higher risk of MDD. No differences between maternal or paternal socioeconomic risk factors were found. Family composition and sibling status showed limited influence on ED risk. DISCUSSION: SES shows opposite associations with AN than MDD, whereas associations with BN and EDNOS are intermediate. The socioeconomic backdrop of AN differs markedly from that reported in other psychiatric disorders. Whether that is due to genetic and/or environmental factors remains unknown. PUBLIC SIGNIFICANCE STATEMENT: Parental socioeconomic background (SES) may influence eating disorders risk in offspring somewhat differently than other psychiatric disorders. In Denmark, higher parental SES was associated with increased risk of, particularly, anorexia nervosa (AN). Importantly AN does strike across the SES spectrum. We must ensure that individuals of all backgrounds have equal access to care and are equally likely to be detected and treated appropriately for eating disorders.

The Strengths and Difficulties Questionnaire Is of Clinical Significance Regarding Emotional and Behavioral Problems in 7-Year-Old Children With Familial Risk of Schizophrenia or Bipolar Disorder and Population-Based Controls the Danish High Risk and Resilience Study-VIA 7; A Population-Based Cohort Study.

Background: Children born to parents with severe mental illness are at increased risk of mental and behavioral difficulties during childhood. We aimed to investigate the occurrence of clinically significant behavioral difficulties in 7-year-old children of parents diagnosed with schizophrenia or bipolar disorder as well as in control children by using the Strengths and Difficulties Questionnaire (SDQ). Further, we aimed to determine if the SDQ could function as a screening instrument for clinically relevant behavioral problems of children at high risk of these severe mental illnesses. Methods: By means of the Danish National Registers, we established a cohort of 522 7-year old children stratified by familial high risk for schizophrenia spectrum disorder (N = 202), bipolar disorder (N =120), and controls (N = 200). The child's primary caregiver completed the SDQ parent version and the Child Behavior Checklist (CBCL) while the schoolteacher completed the SDQ teacher version and the CBCL teacher equivalent; the Teachers Report Form (TRF). Finally, global functioning was assessed with the Children's Global Assessment Scale (CGAS). Results: Children with familial high risk of schizophrenia spectrum disorder or bipolar disorder have a significantly increased risk (OR = 3.8 and 2.3) of suffering clinically significant behavioral difficulties at age 7-years according to SDQ parent ratings. The SDQ discriminates with moderate to high sensitivity and high specificity between familial high-risk children with and without a psychiatric diagnosis and has overall compelling discriminatory abilities in line with the more time consuming CBCL/TRF.Conclusions Familial high-risk children have more behavioral difficulties and more frequently at a level indicative of mental illness compared to control children as measured by the SDQ. The SDQ works well as a screening instrument for clinically relevant behavioral problems in high-risk children.

Environmental factors in offspring of parents with mood disorders and their role in parent-child transmission: findings from a 14-year prospective high-risk study.

BACKGROUND: The factors involved in the transmission of mood disorders are only partially elucidated. Aside from genes, the family environment might play a crucial role in parent-child transmission. Our goals were to (1) assess the associations of parental bipolar disorder (BPD) and Major Depressive Disorder (MDD) with individual or shared family environmental factors, including traumatic events in offspring, parental separation, family cohesion and parental attitudes; and 2) test whether these factors were mediators of the association between exposure to parental mood disorders and the onset of these disorders in offspring. METHODS: The sample stems from an ongoing family high-risk study of mood disorders conducted in the French-speaking part of Switzerland. Given the strong impact of the age of onset of parental disorders on their transmission to children, parental disorders were dichotomized according to the onset (cut-off 21 years). Probands with early-onset (n = 30) and later-onset BPD (n = 51), early-onset (n = 21) and later-onset MDD (n = 47) and controls (n = 65), along with their spouses (n = 193) and offspring (n = 388; < 18 years on study inclusion), were assessed over a mean follow-up duration of 14 years (s.d: 4.6). The environmental measures were based on reports by offspring collected before the onset of their first mood episode. RESULTS: Offspring of probands with later-onset BPD and offspring of probands with both early-onset and later-onset MDD reported traumatic events more frequently than comparison offspring, whereas exposure to parental separation was more frequent in all groups of high-risk offspring. Moreover, several familial environment scores including parenting attitudes differed between offspring of probands with BPD and comparison offspring. However, none of these factors were mediators of the parent-child transmission of BPD. Among the environmental factors, traumatic events were shown to be modest mediators of the transmission of early-onset MDD. CONCLUSIONS: Our data do not support the implication of the assessed environmental factors in the parent-child transmission of BPD. In contrast to BPD, traumatic events partially mediate the parent-child transmission of early-onset MDD, which has important implications for intervention and prevention. Early therapeutic efforts in offspring exposed to these events are likely to reduce their deleterious impact on the risk of subsequent MDD.

Families With Violence Exposure and the Intergenerational Transmission of Somatization.

Introduction: Adults who have histories of childhood trauma have been noted to display greater somatization, dissociative symptoms and affect dysregulation. What happens in the parent-child relationship when those traumatized children become parents? A potential link to somatization in the child has been suggested by several prior studies. Children who have early attachment disturbances had more physical complaints if their mothers displayed less maternal sensitivity during observed parent-child interactions. Yet, the intergenerational link between maternal and child somatization has not been sufficiently explored in a longitudinal study in order to understand the potential impact of maternal trauma history and related psychopathology on subsequent child somatization and psychopathology. Methods: This paper examined prospective, longitudinal data of 64 mother-toddler dyads (mean age = 2.4 years, SD = 0.7) who were later studied when children had a mean age of 7 years. Mothers with and without histories of interpersonal violence (IPV; physical/sexual abuse and/or family violence exposure) were included. Mothers with IPV histories were oversampled. Linear and Poisson regression models were used to test the associations between maternal IPV-related post-traumatic stress disorder (PTSD) with maternal somatization severity when children were toddlers, and between maternal somatization and maternal interactive behaviors with child somatization by maternal report and clinician-rated assessment at school-age. Results: Maternal PTSD severity was significantly associated with increased maternal somatization severity (p = 0.031). Maternal somatization severity during the child's early childhood predicted both maternal report of child somatization (p = 0.011) as well as child thought problems (p = 0.007) when children were school-aged. No association was found between maternal somatization and child-reported psychopathology. The study did not find that maternal alexithymia, caregiving behaviors or child exposure to violence contributed significantly to the model examining the association between maternal and child somatization. Conclusion: The results are in line with the hypothesis of intergenerational transmission of somatization in the context of IPV and related maternal PTSD during formative early development. We interpret this as an expression of psychological distress from mother to child, as maternal trauma and pathology affect the caregiving environment and, thus, the parent-child relationship. The authors conclude with a discussion of implications for parent-infant and early childhood intervention.

Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study.

BACKGROUND AND OBJECTIVES: The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs). METHODS: In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti-streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses. RESULTS: A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037-2.590; definition 2: HR 0.561, 95% CI 0.219-1.436; definition 3: HR 0.853, 95% CI 0.466-1.561; definition 4: HR 0.725, 95% CI 0.384-1.370). DISCUSSION: These results do not suggest an association between GAS exposure and development of tics. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder.

Exploring protective and risk factors in the home environment in high-risk families - results from the Danish High Risk and Resilience Study-VIA 7.

BACKGROUND: Exposure to inadequate home environment may put the healthy development of familial high-risk children at risk. This study aimed to investigate associations between risk factors and an adequate home environment of children having a parent diagnosed with schizophrenia or bipolar disorder. METHODS: From a cohort of 522 children, data from 463 7-year-old children was included. Of these 172 children had familial risk for schizophrenia, 109 children had familial risk for bipolar disorder, and 190 were population-based controls. As part of a comprehensive battery, all participants were assessed with the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory) measuring the quality of the home environment. RESULTS: When analyzing all families together, we found that having a parent diagnosed with schizophrenia would have a negative impact on the home environment (ß = -1.08; 95% CI (-2.16;-0.01); p = 0.05), while familial risk for bipolar disorder did not show significant predictive value. Being a single caregiver and child having experienced severe life events from ages 4 to 7 showed significant negative impact, while child having a mental illness diagnosis did not. Being a female caregiver, good social functioning of the caregiver, high child IQ and not being a single caregiver were found to predict positive values for the home environment. We found similar results when analyzing caregivers with and without a diagnosis separately. CONCLUSIONS: Knowledge of what predicts good home environment should be used to inform development of early interventions for families at risk.

European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part III: pharmacological treatment.

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.