Asthma and asthma-related traits are complex diseases with strong genetic and environmental components. Rapid progress in asthma genetics has led to the identification of several candidate genes that are associated with asthma-related traits. Typically the phenotypic impact of each of these genes, including the ones most often replicated in association studies, is mild, but larger effects may occur when multiple variants synergize within a permissive environmental context. Despite the achievements made in asthma genetics formidable challenges remain. The development of novel, powerful tools for gene discovery, and a closer integration of genetics and biology, should help to overcome these challenges.

Discovering susceptibility genes for asthma and allergy

Many studies have reported that antibiotic use may be associated with increased risk of childhood asthma. Respiratory tract infections in small children may be difficult to distinguish from early symptoms of asthma, and studies may have been confounded by ‘‘protopathic’’ bias, where antibiotics are used to treat early symptoms of asthma. These analyses of a cohort including 1,401 US children assess the association between antibiotic use within the first 6 months of life and asthma and allergy at 6 years of age between 2003 and 2007. Antibiotic exposure was associated with increased risk of asthma (adjusted odds ratio ¼ 1.52, 95% confidence interval (CI): 1.07, 2.16). The odds ratio if asthma was first diagnosed after 3 years of age was 1.66 (95% CI: 0.99, 2.79) and, in children with no history of lower respiratory infection in the first year of life, the odds ratio was 1.66 (95% CI: 1.12, 3.46). The adverse effect of antibiotics was particularly strong in children with no family history of asthma (odds ratio ¼ 1.89, 95% CI: 1.00, 3.58) (Pinteraction ¼ 0.03). The odds ratio for a positive allergy blood or skin test was 1.59 (95% CI: 1.10, 2.28). The results show that early antibiotic use was associated with asthma and allergy at 6 years of age, and that protopathic bias was unlikely to account for the main findings.

Antibiotic Exposure by 6 Months and Asthma and Allergy at 6 Years: Findings in a Cohort of 1,401 US Children

There is a lack of consistency in findings across studies on the prevalence of schizophrenia, and no recent systematic review of the literature exists. The purpose of this study is to provide an updated systematic review of population-based prevalence estimates and to understand the factors that could account for this variation in prevalence estimates. MEDLINE, Embase, and PsycInfo databases were searched for observational studies describing schizophrenia prevalence in general populations from 2003–2013 and supplemented by studies from a prior review covering 1990–2002. Studies reporting prevalence estimates from specialized populations such as institutionalized, homeless, or incarcerated persons were excluded. Prevalence estimates were compared both across and within studies by factors that might contribute to variability using descriptive statistics. Sixty-five primary studies were included; thirty-one (48 %) were from Europe and 35 (54 %) were conducted in samples of ≥50,000 persons. Among 21 studies reporting 12-month prevalence, the median estimate was 0.33 % with an interquartile range (IQR) of 0.26 %–0.51 %. The median estimate of lifetime prevalence among 29 studies was 0.48 % (IQR: 0.34 %–0.85 %). Prevalence across studies appeared to vary by study design, geographic region, time of assessment, and study quality scores; associations between study sample size and prevalence were not observed. Within studies, age-adjusted estimates were higher than crude estimates by 17 %–138 %, the use of a broader definition of schizophrenia spectrum disorders compared to schizophrenia increased case identification by 18 %–90 %, identification of cases from inpatient-only settings versus any setting decreased prevalence by 60 %, and no consistent trends were noted by differing diagnostic criteria. This review provides updated information on the epidemiology of schizophrenia in general populations, which is vital information for many stakeholders. Study characteristics appear to play an important role in the variation between estimates. Overall, the evidence is still sparse; for many countries no new studies were identified.

/pdf/an-evaluation-of-variation-in-published-estimates-of-2lzosqxoe4.pdf

An evaluation of variation in published estimates of schizophrenia prevalence from 1990─2013: a systematic literature review

Bipolar disorder is a multifactorial illness with uncertain aetiology. Knowledge of potential risk factors enables clinicians to identify patients who are more likely to develop bipolar disorder, which directs further investigation, follow up and caution when prescribing. Ideally, identifying directly causative factors for bipolar disorder would enable intervention on an individual or population level to prevent the development of the illness, and improve outcomes through earlier treatment. This article reviews the epidemiology of bipolar disorder, along with putative demographic, genetic and environmental risk factors, while assessing the strength of these associations and to what extent they might be said to be ‘causative’. While numerous genetic and environmental risk factors have been identified, the attributable risk of individual factors is often small, and most are not specific to bipolar disorder but are associated with several mental illnesses. Therefore, while some genetic and environmental factors have strong evidence supporting their association with bipolar disorder, fewer have sufficient evidence to establish causality. There is increasing interest in the role of specific gene–environment interactions, as well as the mechanisms by which risk factors interact to lead to bipolar disorder.

https://journals.sagepub.com/doi/pdf/10.1177/2045125318769235

Epidemiology and risk factors for bipolar disorder

Innate cellular immune responses in newborns

Objective

To estimate the incidence rates (IRs) of bipolar I and bipolar II disorders in the general population according to sociodemographic population characteristics.



Methods

A cohort study (during the years 1996–2007) was conducted in a general practitioners research database with a longitudinal electronic record of 800000 patients throughout the Netherlands [the Integrated Primary Care Information (IPCI) database]. Cases of bipolar disorder were identified and classified by systematic review of medical records. Age- and gender-specific IRs were calculated per calendar year, degree of urbanization, and degree of deprivation.



Results

The overall IR of bipolar disorder was 0.70/10000 person-years (PY) [95% confidence interval (CI): 0.57–0.83]; the IR of bipolar I disorder was 0.43/10000 PY (95% CI: 0.34–0.55) and the IR of bipolar II disorder was 0.19/10000 PY (95% CI: 0.13–0.27). Two peaks in the age at onset of the disorder were noticed: one in early adulthood (15–24 years; 0.68/10000 PY) and a larger peak in later life (45–54 years; 1.2/10000 PY). In bipolar II disorder, only one peak, in the 45–54 year age category (IR 0.42/10000 PY), was found. The IRs of bipolar disorder were significantly higher in deprived areas. Similar rates were found for men compared to women and in urban compared to rural areas. No association was found between the onset of first (hypo)manic episode and month or season of birth.



Conclusions

We found two peaks in the age at onset of bipolar disorder, one in early adulthood and one in later life, the former consisting mainly of bipolar I disorder subjects. The incidence of bipolar disorder is higher in deprived areas. The onset of bipolar disorder is not associated with gender, urbanization, or month or season of birth.

Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study

Neonates are highly susceptible to diseases and display biased type 2 immune responses, although no skewing to type 2 cytokines has been reported. In view of the emerging importance of IL-13 in type 2 inflammatory responses and clinical allergy, we analyzed IL-13 production by neonatal T cells. We found that, mainly CD8 T cells produced high levels of IL-13, while producing low levels of IL-4, IL-10 and IFN-gamma, upon primary and secondary stimulation. Our results point towards a possible immunoregulatory role of CD8 T cells in neonate responses. Moreover, they suggest that the abundance of IL-13 in the neonate immune system might account for the type 2 bias in neonates, providing a basis for the high disease susceptibility of newborns, for instance to allergic diseases.

High IL-13 production by human neonatal T cells: neonate immune system regulator?

Background
Longitudinal incidence studies of schizophrenia spectrum disorders (SSD) performed in mental health service organizations are prone to confounding factors not found in research performed in the general population.

Jojanneke S. Kroon

Papers

Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study

High IL-13 production by human neonatal T cells: neonate immune system regulator?

Annual incidence rate of schizophrenia and schizophrenia spectrum disorders in a longitudinal population-based cohort study