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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Recent literature suggests that over 70% of cases of antibody-mediated encephalitis present to psychiatry services with features of psychosis predominantly.
To investigate the seroprevalence of N-Methyl-D-Aspartate receptor antibodies (NMDAr-Ab) in patients with first episode psychosis (FEP)
Following ethical approval, all cases meeting entry criteria were invited to participate. Participants were interviewed with SCID to obtain a DSM diagnosis. NMDAr-Ab were identified in serum by cell based assay using co-transfected Human Embryonic Kidney (HEK)cells. Positive cases were reviewed by clinical neurology. Decision to treat with immunotherapy was made on a case by case basis.
85/115 (72%) of patients with FEP entered the study. 49 (58%) participants were male, mean age (SD) 37 (15.7) years. 42 (52%) were outpatients at the time of assessment. Four cases (5%) were serum NMDAr-Ab positive. 3 of these cases were male, age 48 (16.3) years. All four were admitted as inpatients with normal brain MRI imaging. One case (female, 55) was confirmed as NMDAr-Ab encephalitis based on case presentation, EEG demonstrating bilateral cerebral dysfunction and NMDAr-Ab in CSF. Immunotherapy treatment lead to clinical improvement. In remaining cases, EEG was normal and CSF negative. All 3 of these cases showed clinical improvement following psychiatric treatment as usual.
Our findings support the current estimates as to NMDAr-Ab prevalence in FEP. Increased awareness has lead to rapid treatment of florid cases of NMDAr-Ab encephalitis in our service. Additional seropositive cases are being followed with neuro-cognitive testing for any evidence of decline.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
To compare the microbiological efficacy, turnaround time, cost, convenience, and patient and user tolerance of Tristel Trio Wipes, PeraSafe solution and Cidex OPA solution for the high-level disinfection of flexible nasendoscopes.
Flexible nasendoscopes were used in routine clinical encounters. They were then disinfected with one of the three disinfectant methods. Surveillance cultures were taken before and after each disinfection process. Data relating to each of the study parameters were recorded.
Positive bacterial cultures were discovered on nasendoscopes disinfected with PeraSafe and Cidex OPA. Tristel Trio Wipes have no capital outlay cost, the lowest running cost, the greatest convenience and the fastest turnaround time. PeraSafe had a faster turnaround time than Cidex OPA, and lower running costs.
Tristel Trio Wipes are equal to PeraSafe and Cidex OPA in terms of microbiological efficacy. Turnaround time and cost are dramatically reduced when using Tristel Trio Wipes compared to the other disinfectant methods.
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
Coral reef ecosystems have great importance for the countries of the Wider Caribbean Region in terms of both use and non-use values and services. Several of the contributors to this symposium attest to their importance for fisheries and biodiversity (see Ehrhardt et al. in Chapter 11; Appeldoorn in Chapter 10; Appeldoorn et al. in Chapter 12; Horrocks et al. in Chapter 9). Coral reef ecosystems support livelihoods (see McConney and Salas in Chapter 7) and provide critical ecosystem services (Schuhmann et al. in Chapter 8) including for tourism, although this aspect of their value is not developed in detail in Chapter 8. Caribbean coral reef ecosystems have been degraded by many human impacts of both marine and land-based origin (see Sweeney and Corbin in Chapter 4; Gil and Wells in Chapter 5; Yáñez-Arancibia et al. in Chapter 17). They are among the most complex and biologically diverse marine ecosystems, and will require a holistic ecosystem- based approach for their conservation and sustainable use.
This synthesis chapter presents the outputs of a group process aimed at developing a vision and way ahead for ecosystem-based management (EBM) for coral reef ecosystems in the Wider Caribbean, using the methods described earlier (Fanning et al. in Chapter 1). The chapter first describes a vision for coral reef EBM and reports on the priorities assigned to the identified vision elements. It then discusses how the vision might be achieved by taking into account assisting factors (those that facilitate achievement) and resisting factors (those that inhibit achievement). The chapter concludes with guidance on the strategic direction needed to implement the vision, identifying specific actions to be undertaken for each of the vision elements.
The occupational breakdown of members of the Coral Reef Ecosystems Working Group reflected the diversity of affiliations present at the EBM Symposium and included governmental, intergovernmental, academic, non-governmental and private sector (fishers and fishing industry and consulting) representatives. With guidance provided by the facilitator, this diverse group of participants was asked to first address the question of “What do you see in place in 10 years’ time when EBM/EAF has become a reality in the Caribbean?”
Integrated Multi-Trophic Aquaculture takes advantage of the mutualism between some detritivorous fish and phytoplankton. The fish recycle nutrients by consuming live (and dead) algae and provide the inorganic carbon to fuel the growth of live algae. In the meanwhile, algae purify the water and generate the oxygen required by fishes. Such mechanism stabilizes the functioning of an artificially recycling ecosystem, as exemplified by combining the euryhaline tilapia Sarotherodon melanotheron heudelotii and the unicellular alga Chlorella sp. Feed addition in this ecosystem results in faster fish growth but also in an increase in phytoplankton biomass, which must be limited. In the prototype described here, the algal population control is exerted by herbivorous zooplankton growing in a separate pond connected in parallel to the fish–algae ecosystem. The zooplankton production is then consumed by tilapia, particularly by the fry and juveniles, when water is returned to the main circuit. Chlorella sp. and Brachionus plicatilis are two planktonic species that have spontaneously colonized the brackish water of the prototype, which was set-up in Senegal along the Atlantic Ocean shoreline. In our system, water was entirely recycled and only evaporation was compensated (1.5% volume/day). Sediment, which accumulated in the zooplankton pond, was the only trophic cul-de-sac. The system was temporarily destabilized following an accidental rotifer invasion in the main circuit. This caused Chlorella disappearance and replacement by opportunist algae, not consumed by Brachionus. Following the entire consumption of the Brachionus population by tilapias, Chlorella predominated again. Our artificial ecosystem combining S. m. heudelotii, Chlorella and B. plicatilis thus appeared to be resilient. This farming system was operated over one year with a fish productivity of 1.85 kg/m2 per year during the cold season (January to April).
Repetitive transcranial magnetic stimulation (rTMS) has been shown to be an effective treatment for depression. However, there has been little research to determine optimal parameters for treatment.
This study compared two rTMS treatment regimes for the treatment of major depression. Seventy-seven participants were randomized to either spaced or daily treatment. Spaced rTMS was given 3 days/week for 6 weeks (18 treatments in total) and daily rTMS was given 5 days/week for 4 weeks (20 treatments in total). All participants were assessed at baseline and after 4 weeks of treatment. Participants in the spaced treatment group were also assessed after 6 weeks of treatment. All participants were treated at 110% of the resting motor threshold with high-frequency rTMS (10 Hz) to the left dorsolateral prefrontal cortex (DLPFC) followed by low-frequency rTMS to the right DLPFC.
Participants in the daily treatment group showed more improvement by week 4 than those in the spaced treatment group; however, both groups had similar improvement by treatment completion. There was significant improvement in both groups in ratings of depression and anxiety, with no significant differences between groups.
Our study indicates that the efficacy of rTMS is related to the number of treatments given and that spacing the treatments neither improves nor reduces efficacy.
We have developed a chemical kinetics simulation that can be used as both an educational
and research tool. The simulator is designed as an accessible, open-source project that
can be run on a laptop with a student-friendly interface. The application can potentially
be scaled to run in parallel for large simulations. The simulation has been successfully
used in a classroom setting for teaching basic electrochemical properties. We have shown
that this can be used for simulating fundamental molecular and chemical processes and even
simplified models of predator–prey interactions. By giving the simulated entities spatial
extent in the lattice, the particles do not interpenetrate, and clusters of particles can
spatially exclude one another. Our simulation demonstrates that spatial inhomogeneity
leads to different results than those that are obtained by using standard ordinary
differential equation models, as previously reported.
Quantitative trait loci (QTLs) mapping often results in data on a number of traits that have well-established causal relationships. Many multi-trait QTL mapping methods that account for correlation among the multiple traits have been developed to improve the statistical power and the precision of QTL parameter estimation. However, none of these methods are capable of incorporating the causal structure among the traits. Consequently, genetic functions of the QTL may not be fully understood. In this paper, we developed a Bayesian multiple QTL mapping method for causally related traits using a mixture structural equation model (SEM), which allows researchers to decompose QTL effects into direct, indirect and total effects. Parameters are estimated based on their marginal posterior distribution. The posterior distributions of parameters are estimated using Markov Chain Monte Carlo methods such as the Gibbs sampler and the Metropolis–Hasting algorithm. The number of QTLs affecting traits is determined by the Bayes factor. The performance of the proposed method is evaluated by simulation study and applied to data from a wheat experiment. Compared with single trait Bayesian analysis, our proposed method not only improved the statistical power of QTL detection, accuracy and precision of parameter estimates but also provided important insight into how genes regulate traits directly and indirectly by fitting a more biologically sensible model.
Twin and sibling studies have identified specific cognitive phenotypes that may mediate the association between genes and the clinical symptoms of attention deficit hyperactivity disorder (ADHD). ADHD is also associated with lower IQ scores. We aimed to investigate whether the familial association between measures of cognitive performance and the clinical diagnosis of ADHD is mediated through shared familial influences with IQ.
Multivariate familial models were run on data from 1265 individuals aged 6–18 years, comprising 920 participants from ADHD sibling pairs and 345 control participants. Cognitive assessments included a four-choice reaction time (RT) task, a go/no-go task, a choice–delay task and an IQ assessment. The analyses focused on the cognitive variables of mean RT (MRT), RT variability (RTV), commission errors (CE), omission errors (OE) and choice impulsivity (CI).
Significant familial association (rF) was confirmed between cognitive performance and both ADHD (rF=0.41–0.71) and IQ (rF=−0.25 to −0.49). The association between ADHD and cognitive performance was largely independent (80–87%) of any contribution from etiological factors shared with IQ. The exception was for CI, where 49% of the overlap could be accounted for by the familial variance underlying IQ.
The aetiological factors underlying lower IQ in ADHD seem to be distinct from those between ADHD and RT/error measures. This suggests that lower IQ does not account for the key cognitive impairments observed in ADHD. The results have implications for molecular genetic studies designed to identify genes involved in ADHD.
In an inter-laboratory survey, the pour plate, surface spread, agar droplet and spiral plate methods were used in parallel with the surface drop method for enumeration of micro-organisms in foods. Good agreement was obtained between all surface methods of enumeration, but there was poor agreement between molten agar methods and the surface drop method.
A total of 1143 samples of food that were ready for consumption at the point of retail sale were examined. Eight types of food products were chosen: meat pasties, sausage rolls, real-cream slices, synthetic-cream slices, mayonnaise-based coleslaws, faggots, patés and continental sausages. The results of this survey suggest that the upper limit for an acceptable viable count should vary according to the food product. Salmonellae were not isolated on any occasion. Potentially harmful organisms were not isolated at levels expected to constitute a public health hazard.
Information concerning the nature of the product, the total viable count, the presence or absence of pathogenic, toxigenic or indicator organisms, the spectrum of the bacterial flora and the relative predominance of each organism must all be considered when assessing the microbiological acceptability of retail ‘ready to eat’ products.
The use of the methylene blue test for the examination of cows milk was investigated in an inter-laboratory survey. A poor relationship was found between results of these tests and total viable counts. Coliforms were detected in a large number of pasteurized milks, indicating frequent post-pasteurization contamination. No relationship was found between the results of the methylene blue test and the presence of coliforms.
Results from this survey highlight the need for reappraisal of the methylene blue test as a statutory method for the examination of milk. A total viable count and coliform test are suggested for providing information regarding dairy hygiene and the quality of the product at the point of retail sale.