The etiology and clinical course of bipolar disorder are considered to be determined by genetic and environmental factors. Although the kindling hypothesis emphasizes the impact of environmental ...factors on initial onset, their connection to the outcome and clinical course have been poorly established. Hence, there have been numerous research efforts to investigate the impact of environmental factors on the clinical course of illness. Our aim is to outline recent research on the impact of environmental determinants on the clinical course of bipolar disorder. We carried out a computer‐aided search to find publications on an association between environmental factors, life events, and the clinical course of bipolar disorder. Publications in the reference lists of suitable papers have also been taken into consideration. We performed a narrative overview on all eligible publications. The available body of data supports an association between environmental factors and the clinical course of bipolar disorder. These factors comprise prenatal, early‐life, and entire lifespan aspects. Given varying sample sizes and several methodological limitations, the reported quality and extent of the association between environmental factors and the clinical course of bipolar disorder should be interpreted with utmost caution. Systematic longitudinal long‐term follow‐up trials are needed to obtain a clearer and more robust picture.
•Clinical response to lithium treatment in bipolar disorder is heterogeneous.•Genetics may explain such a heterogeneity.•Genomic approaches have already identified suggestive regions in our DNA ...associated with lithium response.•Recent advances in cellular models, high throughput analysis, and statistical methodologies may catalyze advances in this field.
Lithium is an effective mood stabilizer in bipolar disorder (BD). There is, however, high variability in treatment response to lithium and only 20–30% of individuals with BD are excellent responders. This subgroup has been shown to have specific phenotypic characteristics, and family studies have implicated genetics as an important factor. However, candidate gene studies did not find evidence for major effect genes. Genome-wide association studies (GWAS) have emphasized that lithium response is a polygenic trait. GWAS based on larger sample sizes and non-European ancestries are likely to shed light on the genomic architecture of this trait. Furthermore, induced pluripotent stem cells, transcriptomics, epigenetics, the integration of multiple omics data, and their combination with advanced machine learning techniques hold promise for the understanding of the complex biological underpinnings of lithium treatment response.
Background Patients with schizophrenia often suffer from cognitive dysfunction, including impaired learning and memory. We recently demonstrated that long-term potentiation in rat hippocampus, a ...mechanistic model of learning and memory, is linked to gene expression changes in immunity-related processes involved in complement activity and antigen presentation. We therefore aimed to examine whether key regulators of these processes are genetic susceptibility factors in schizophrenia. Methods Analysis of genetic association was based on data mining of genotypes from a German genome-wide association study and a multiplex GoldenGate tag single nucleotide polymorphism (SNP)-based assay of Norwegian and Danish case–control samples (Scandinavian Collaboration on Psychiatric Etiology), including 1133 patients with schizophrenia and 2444 healthy control subjects. Results Allelic associations were found across all three samples for eight common SNPs in the complement control-related gene CSMD2 ( CUB and Sushi Multiple Domains 2 ) on chromosome 1p35.1-34.3, of which rs911213 reached a statistical significance comparable to that of a genome wide threshold ( p value = 4.0 × 10−8 ; odd ratio = .73, 95% confidence interval = .65–.82). The second most significant gene was CSMD1 on chromosome 8p23.2, a homologue to CSMD2 . In addition, we observed replicated associations in the complement surface receptor CD46 as well as the major histocompatibility complex genes HLA-DMB and HLA-DOA. Conclusions These data demonstrate a significant role of complement control-related genes in the etiology of schizophrenia and support disease mechanisms that involve the activity of immunity-related pathways in the brain.
Subclinical psychotic experiences (PLEs) are among the frequently reported mental health problems in children/adolescents. PLEs identified in cross sectional studies of children/adolescents are ...associated with current and future mental health problems. These associations are stronger for PLEs that persist over time. Hence, it could be useful to examine which children/adolescents with PLEs at a first assessment (baseline) are more likely to have PLEs at subsequent assessments.
We conducted a scoping review of studies that examined whether characteristics of children/adolescents (≤18 years) with PLEs at baseline predict whether PLEs are likely to be persistent or remittent at subsequent assessments. We included studies published between January 2002 and December 2017, conducted on general child/adolescent populations of ≥300 individuals, that provided data on PLEs for at least 2 time points, had available follow-up data for ≥50% of those assessed for PLEs at baseline and targeted for follow-up examination, and reported the differences between individuals with PLEs that persisted or remitted during the study period.
Six studies met our criteria. Each of them investigated a wide range of baseline characteristics but no predictor of persistence was replicated.
Our knowledge about which children/adolescents with PLEs at an initial assessment are likely to have persistent PLEs at subsequent assessments is sparse. A handful of predictors of persistent PLEs have been investigated so far, and none replicated. A better understanding of these predictors would be an important complement to investigations examining the evolution of PLEs and of mental health problems in children/adolescents.
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