Translating insights from neuropsychiatric genetics and genomics for precision psychiatry

The primary aim of precision medicine is to tailor healthcare more closely to the needs of individual patients. This requires progress in two areas: the development of more precise treatments and the ability to identify patients or groups of patients in the clinic for whom such treatments are likely to be the most effective. There is widespread optimism that advances in genomics will facilitate both of these endeavors. It can be argued that of all medical specialties psychiatry has most to gain in these respects, given its current reliance on syndromic diagnoses, the minimal foundation of existing mechanistic knowledge, and the substantial heritability of psychiatric phenotypes. Here, we review recent advances in psychiatric genomics and assess the likely impact of these findings on attempts to develop precision psychiatry. Emerging findings indicate a high degree of polygenicity and that genetic risk maps poorly onto the diagnostic categories used in the clinic. The highly polygenic and pleiotropic nature of psychiatric genetics will impact attempts to use genomic data for prediction and risk stratification, and also poses substantial challenges for conventional approaches to gaining biological insights from genetic findings. While there are many challenges to overcome, genomics is building an empirical platform upon which psychiatry can now progress towards better understanding of disease mechanisms, better treatments, and better ways of targeting treatments to the patients most likely to benefit, thus paving the way for precision psychiatry

Everybody Phones Out: teaching experiments with Instagram

This paper considers the pedagogical prototype, Everybody Phones Out (EPO), that took place between February - April 2016 on the BA (Hons) Culture, Criticism and Curation course at Central Saint Martins. EPO utilised a dedicated Instagram account, as a means to support the delivery of a series of traditional lectures to first year undergraduate students. Taking EPO as a case study this paper assesses the potential for IBMSNs (image-based mobile-socialnetwork) to be employed in, and beyond, the classroom for the delivery of content and engagement with students. This paper makes specific reference to EPO's co-option of the iconography of memes, the combination of textual and visual information and the image parlance of memeology to humorous, and virulent, affect. Evaluating our own successes and failures, we detail a code of conduct for others considering Instagram usage in education

Walking Through Black History Digital Humanities Project

The focus of the project was to illustrate African American history including four periods: Antebellum, Reconstruction, Jim Crow and Civil Rights. We focused on choosing sites that could illustrate that history most effectively, noting that the Reconstruction era is often the most challenging of the four periods in that it is short-lived with little material culture left

Genetics of schizophrenia

Schizophrenia is a common psychiatric disorder with a strong genetic component. Recent studies applying new genomic technology to large samples have yielded substantial advances in identifying specific, associated DNA variants as well as clarifying the underlying genetic architecture of the disorder. The genetic liability of schizophrenia is now established as polygenic, with risk alleles in many genes existing across the full allelic frequency spectrum. It has also become apparent that schizophrenia shares risk alleles with other neuropsychiatric phenotypes, such as bipolar disorder, major depressive disorder, autism spectrum disorder, intellectual disability and attention-deficit hyperactivity disorder. These risk variants aggregate in several sets of functionally related genes, thereby providing novel insights into disease pathogenesis and opportunities for research into discovering new treatments

Evaluation of an Emotional Support Service for the Visually Impaired

Purpose. To evaluate the impact of a facilitated peer group emotional support service on visual quality of life (VQoL). Methods. Consecutive participants in an emotional support service delivered to groups of up to 6 and facilitated by trained counsellors were recruited (n=29). The VCM1 instrument was administered to participants at the start of the service, at the end of the service, and 6 months after completion of the service. Results. For the group as a whole, VQoL significantly improved between the beginning of the service and the end (F(1, 23) =16.43, p=.000), but was no better than at the start six months later (F(1,23)=3.60, p=.07). However, those with poorer initial VQoL showed significantly greater improvements after six months (1.74±2.21 logits) than those with higher initial VQoL (-0.12±0.71 logits) (t(23)=2.89, p=.008). The effect size of the intervention for those with poor initial VQoL was 1.10 at the end of service, and 0.92 after six months. The items which became and remained easier were feeling lonely or isolated due to eyesight, feeling sad or low due to eyesight, and feeling worried about general safety outside the home. Conclusions. This facilitated peer group emotional support service significantly improves VQoL as assessed with the VCM1 over at least 6 months for those with poorer initial VQoL. Different interventions may be needed for those with initially good VQoL, and to improve other aspects of quality of life not influenced by the service

Using 'Omic Approaches to Compare Temporal Bacterial Colonization of Lolium perenne, Lotus corniculatus and Trifolium pratense in the Rumen

Understanding rumen plant-microbe interactions is central for development of novel methodologies allowing improvements in ruminant nutrient use efficiency. This study investigated rumen bacterial colonization of fresh plant material and changes in plant chemistry over a period of 24 h period using three different fresh forages: Lolium perenne (perennial ryegrass; PRG), Lotus corniculatus (bird's foot trefoil; BFT) and Trifolium pratense (red clover; RC). We show using 16S rRNA gene ion torrent sequencing that plant epiphytic populations present pre-incubation (0 h) were substantially different to those attached post incubations in the presence of rumen fluid on all forages. Thereafter primary and secondary colonization events were evident as defined by changes in relative abundances of attached bacteria and changes in plant chemistry, as assessed using Fourier transform infrared (FTIR) spectroscopy. For PRG colonization, primary colonization occurred for up to 4 h and secondary colonization from 4 h onward. The changes from primary to secondary colonization occurred significantly later with BFT and RC, with primary colonization being up to 6 h and secondary colonization post 6 h of incubation. Across all 3 forages the main colonizing bacteria present at all time points post-incubation were Prevotella, Pseudobutyrivibrio, Ruminococcus, Olsenella, Butyrivibrio, and Anaeroplasma (14.2, 5.4, 1.9, 2.7, 1.8, and 2.0% on average respectively), with Pseudobutyrivibrio and Anaeroplasma having a higher relative abundance during secondary colonization. Using CowPI, we predict differences between bacterial metabolic function during primary and secondary colonization. Specifically, our results infer an increase in carbohydrate metabolism in the bacteria attached during secondary colonization, irrespective of forage type. The CowPI data coupled with the FTIR plant chemistry data suggest that attached bacterial function is similar irrespective of forage type, with the main changes occurring between primary and secondary colonization. These data suggest that the sward composition of pasture may have major implications for the temporal availability of nutrients for animal.</p

Gender differences in CNV burden do not confound schizophrenia CNV associations

Compared with the general population, an excess of rare copy number variants (CNVs) has been identified in people with schizophrenia. Females with neurodevelopmental disorders and in the general population have been reported to carry more large, rare CNVs than males. Given that many schizophrenia datasets do not have equal gender ratios in cases and controls, sex differences in CNV burden might have impacted on estimates of case-related CNV burden and also on associations to individual loci. In a sample of 13,276 cases and 17,863 controls, we observed a small but significant excess of large (≥500 Kb), rare (<1%) CNVs in females compared with males in both cases and controls (OR = 1.17, P = 0.0012 for controls; OR = 1.11, P = 0.045 for cases). The burden of 11 schizophrenia-associated CNVs was significantly higher in female cases compared with male cases (OR = 1.38, P = 0.0055), but after accounting for the rates of CNVs in controls, we found no significant gender difference in the risk conferred by these loci. Controlling for gender had a negligible effect on the significance of association between specific CNVs and schizophrenia. The female excess of large CNVs in both cases and controls suggests a female protective mechanism exists for deleterious CNVs that may extend beyond neurodevelopmental phenotypes

A brief report: de novo copy number variants in children with attention deficit hyperactivity disorder

Recent case–control genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated common and rare genetic risk alleles, highlighting the polygenic and complex aetiology of this neurodevelopmental disorder. Studies of other neurodevelopmental disorders, such as autism spectrum disorder (ASD), Tourette disorder, developmental delay/intellectual disability and schizophrenia indicate that identification of specific risk alleles and additional insights into disorder biology can be gained by studying non-inherited de novo variation. In this study, we aimed to identify large de novo copy number variants (CNVs) in children with ADHD. Children with a confirmed diagnosis of ADHD and their parents were genotyped and included in this sample. We used PennCNV to call large (>200 kb) CNVs and identified those calls that were present in the proband and absent in both biological parents. In 305 parent–offspring trios, we detected 14 de novo CNVs in 13 probands, giving a mutation rate of 4.6% and a per individual rate of 4.3%. This rate is higher than published reports in controls and similar to those observed for ASD, schizophrenia and Tourette disorder. We also identified de novo mutations at four genomic loci (15q13.1–13.2 duplication, 16p13.11 duplication, 16p12.2 deletion and 22q11.21 duplication) that have previously been implicated in other neurodevelopmental disorders, two of which (16p13.11 and 22q11.21) have also been implicated in case–control ADHD studies. Our study complements ADHD case–control genomic analyses and demonstrates the need for larger parent–offspring trio genetic studies to gain further insights into the complex aetiology of ADHD

Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank

Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations have been observed between neuroanatomical phenotypes and known genetic risk factors for schizophrenia. We tested subcortical brain volume differences between 49 unaffected participants carrying at least one of the 12 copy number variants associated with schizophrenia in UK Biobank and 9063 individuals who did not carry any of the 93 copy number variants reported to be pathogenic. Our results show that CNV carriers have reduced volume in some of the subcortical structures previously shown to be reduced in schizophrenia. Moreover, these associations partially accounted for the association between pathogenic copy number variants and cognitive impairment, which is one of the features of schizophrenia