The KINGS Mouse: A Novel Model of β-Cell Endoplasmic Reticulum Stress and Human Diabetes.

Animal models are important tools in diabetes research because ethical and logistical constraints limit access to human tissue. β-Cell dysfunction is a common contributor to the pathogenesis of most types of diabetes. Spontaneous hyperglycemia was developed in a colony of C57BL/6J mice at King's College London (KCL).

Genetic association and functional characterization of MCPH1 gene variation in bipolar disorder and schizophrenia.

A rare microcephalin 1 gene (MCPH1) variant rs61749465A>G (p.Asp61Gly) with prior evidence for association with schizophrenia (p = 3.78 × 10 ) was tested for association in 2,300 bipolar disorder (BPD) participants, 1,930 SCZ participants and 1,820 normal comparison subjects.

Mutation intolerant genes and targets of FMRP are enriched for nonsynonymous alleles in schizophrenia.

Risk of schizophrenia is conferred by alleles occurring across the full spectrum of frequencies from common SNPs of weak effect through to ultra rare alleles, some of which may be moderately to highly penetrant. Previous studies have suggested that some of the risk of schizophrenia is attributable to uncommon alleles represented on Illumina exome arrays. Here, we present the largest study of exomic variation in schizophrenia to date, using samples from the United Kingdom and Sweden (10,011 schizophrenia cases and 13,791 controls).

Government won't listen.

How many nurses do you know who would walk out of a clinical area, leaving patients alone with minimal cover? The junior doctors tried and failed at strike action so why would the government listen to workers whom they have never shown any respect or regard for. There will come a time when there will be no one left to care - this is the true concern.

Identification of rare nonsynonymous variants in SYNE1/CPG2 in bipolar affective disorder.

Background: Bipolar affective disorder (BPD) is a severe mood disorder with a prevalence of ∼1.5% in the population. The pathogenesis of BPD is poorly understood; however, a strong heritable component has been identified.

Genetic variation in the miR-708 gene and its binding targets in bipolar disorder.

Objective: rs12576775 was found to be associated with bipolar disorder (BD) in a genome-wide association study (GWAS). The GWAS signal implicates genes for the microRNAs miR-708 and miR-5579 and the first exon of the Odd Oz/ten-m homolog 4 gene (ODZ4). In the present study, miR-708, its surrounding region, and its targets were analyzed for potential BD-associated functional variants.

Association of rare variation in the glutamate receptor gene SLC1A2 with susceptibility to bipolar disorder and schizophrenia.

The SLC1A2 gene encodes the excitatory amino acid transporter 2 (EAAT2). Glutamate is the major mediator of excitatory neurotransmission and EAAT2 is responsible for clearing the neurotransmitter from the synaptic cleft. Genetic variation in SLC1A2 has been implicated in a range of neurological and neuropsychiatric conditions including schizophrenia (SZ), autism and in core phenotypes of bipolar disorder (BD).

Genetic association of the tachykinin receptor 1 TACR1 gene in bipolar disorder, attention deficit hyperactivity disorder, and the alcohol dependence syndrome.

Single nucleotide polymorphisms (SNPs) in the tachykinin receptor 1 gene (TACR1) are nominally associated with bipolar affective disorder (BPAD) in a genome-wide association study and in several case-control samples of BPAD, alcohol dependence syndrome (ADS) and attention-deficit hyperactivity disorder (ADHD). Eighteen TACR1 SNPs were associated with BPAD in a sample (506 subjects) from University College London (UCL1), the most significant being rs3771829, previously associated with ADHD. To further elucidate the role of TACR1 in affective disorders, rs3771829 was genotyped in a second BPAD sample of 593 subjects (UCL2), in 997 subjects with ADS, and a subsample of 143 individuals diagnosed with BPAD and comorbid alcohol dependence (BPALC).

Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population.

Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk.

The effect of clozapine on mRNA expression for genes encoding G protein-coupled receptors and the protein components of clathrin-mediated endocytosis.

Objectives: Clathrin-mediated endocytosis (CME) is an intracellular trafficking mechanism for packaging cargo, including G protein-coupled receptors (GPCRs), into clathrin-coated vesicles (CCVs). The antipsychotic chlorpromazine inhibits CCV assembly of adaptor protein AP2 whereas clozapine increases serotonin2A receptor internalization. We hypothesized that clozapine alters the expression of CME genes modulating vesicle turnover and GPCR internalization.

Determining the association of the 5HTTLPR polymorphism with delusions and hallucinations in Lewy body dementias.

Objectives: To determine whether the 5HTTLPR serotonin transporter polymorphism is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD).

Design: Prospective cohort study.

Participants: A total of 187 individuals, recruited from centres in Norway, Sweden, and the United Kingdom were included in this study; 97 with clinically or neuropathologically diagnosed DLB/PDD and 90 cognitively normal individuals as a comparison group.

Genetic association, mutation screening, and functional analysis of a Kozak sequence variant in the metabotropic glutamate receptor 3 gene in bipolar disorder.

Importance: Genetic markers at the gene encoding the metabotropic glutamate receptor 3 (GRM3) showed allelic association with bipolar disorder.

Objective: To screen the GRM3 gene and adjacent control regions of genomic DNA in volunteers with bipolar affective disorder for mutations increasing susceptibility to bipolar disorder.

Design: Sequencing and high-resolution melting curve analysis of DNA followed by genotyping was carried out in 1099 patients with bipolar affective disorder and 1152 healthy comparator individuals.

No association of COMT val158met polymorphism and psychotic symptoms in Lewy body dementias.

We sought to determine whether the COMT val158met polymorphism (rs4680) is associated with delusions and hallucinations in people with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). A total of 218 individuals, recruited from centres in Norway, Sweden and the UK were included in this study; 121 with clinically or neuropathologically diagnosed DLB/PDD and 97 age-matched, cognitively normal controls. All participants with dementia underwent serial evaluation of neuropsychiatric symptoms to assess the presence of persistent delusions and hallucinations using the Columbia University Scale for Psychopathology in Alzheimer's disease, the Neuropsychiatric Inventory or the Present Behavioural Examination.

Sequencing of the ANKYRIN 3 gene (ANK3) encoding ankyrin G in bipolar disorder reveals a non-conservative amino acid change in a short isoform of ankyrin G.

Significant association between polymorphisms at the ANK3 gene with bipolar disorder has previously been reported and confirmed in several samples. Here we report on association between ANK3 and bipolar disorder in a new sample of 593 patients and 642 controls (UCL2) as well as the results of sequencing of the exons and flanking regions of ANK3 from bipolar patients. Single nucleotide polymorphisms (SNPs) associated with bipolar disorder in our original GWA study (UCL1) were genotyped and tested for association in the new sample.

Hypertension is a potential risk factor for vascular dementia: systematic review.

Objective: The aim of the study was to conduct a meta-analysis of epidemiological and case control studies to determine whether arterial hypertension is specifically associated with an increased risk of vascular dementia (VaD).

Design: Longitudinal and cross-sectional prospective studies using operationalised criteria to define VaD and hypertension, with a normal control comparison group were systematically reviewed. Cochrane Library, Embase, Medline, and PsycInfo data sources were searched along with reference lists of included articles and reviews.