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There is a need to develop feeding strategies to prevent the adverse effect of concentrate feeding in high-performance horses fed energy-dense diets aiming to maintain their health and welfare. The objective of this study is to determine the effect of a VistaEQ product containing 4% live yeast Saccharomyces cerevisiae (S. cerevisiae), with activity 5 × 108 colony-forming unit/g and fed 2 g/pony per day, on faecal microbial populations when supplemented with high-starch and high-fibre diets using Illumina next generation sequencing of the V3-V4 region of the 16S ribosomal RNA gene. The four treatments were allocated to eight mature Welsh section A pony geldings enrolled in a 4-period × 8 animal crossover design. Each 19-day experimental period consisted of an 18-day adaptation phase and a single collection day, followed by a 7-day wash out period. After DNA extraction from faeces and library preparation, α-diversity and linear discriminant analysis effect size were performed using 16S metagenomics pipeline in Quantitative Insights Into Microbial Ecology (QIIME™) and Galaxy/Hutlab. Differences between the groups were considered significant when linear discriminant analysis score was >2 corresponding to P < 0.05. The present study showed that S. cerevisiae used was able to induce positive changes in the equine microbiota when supplemented to a high-fibre diet: it increased relative abundance (RA) of Lachnospiraceae and Dehalobacteriaceae family members associated with a healthy core microbiome. Yeast supplementation also increased the RA of fibrolytic bacteria (Ruminococcus) when fed with a high-fibre diet and reduced the RA of lactate producing bacteria (Streptococcus) when a high-starch diet was fed. In addition, yeast increased the RA of acetic, succinic acid producing bacterial family (Succinivibrionaceae) and butyrate producing bacterial genus (Roseburia) when fed with high-starch and high-fibre diets, respectively. VistaEQ supplementation to equine diets can be potentially used to prevent acidosis and increase fibre digestibility. It may help to meet the energy requirements of performance horses while maintaining gut health.
Fibre is essential to maintain healthy gut; however, energy demands of performance horses can be too high to be met by forages alone. Yeast may support the function of cellulolytic bacteria to digest fibre. The aim of this work was to determine the effect of an oral supplement (VistaEQ) containing 4% live yeast on the in vitro and in vivo digestibility of high-starch (HS) and high-fibre diets (HF). Eight ponies were used in a 4 × 4 Latin square design consisting of 4- × 19-day periods and four diets: HF, HF + yeast (HFY), HS and HS + yeast (HSY). In vivo apparent digestibility (AD) was estimated using total collection technique, and faecal particle size was measured using NASCO digestive analyser. Faeces from the ponies were subsequently used as an inoculum in ANKOM RF gas production system to assess fermentation kinetics in vitro. Each module contained 1 g of feed substrate DM in the following combinations: 50% grass hay and 50% alfalfa (HF_50 : 50) or concentrate (HS_50 : 50), and 75% grass hay and 25% alfalfa (HF_75 : 25) or concentrate (HS_75 : 25) with or without yeast. Yeast was able to induce more gas production from HF_75 : 25, HS_75 : 25 and HF_50 : 50 feed substrates incubated with respective faecal inoculum base. Yeast did not affect pH in vitro when the substrates were incubated in 50 : 50 ratio, while the pH was higher for HF_75 : 25 incubated with correspondent faecal inoculum compared to HS_75 : 25 and HSY_75 : 25. Yeast had no effects on ADF and CP AD of either diet. Yeast addition increased DM (HF: 0.2%, HS: 0.4%), organic matter (HF: 0.7%, HS: 1.3%), NDF (HF: 0.5%, HS: 1.5%), total detergent fibre (HF: 0.7%; HS: 0.4%) (P < 0.05) and also tended to increase hemicellulose AD (HF: 0.9%, HS: 1.2%) (P < 0.10). Faecal pH in vivo was higher for both HF diets compared to HS diet without yeast supplementation (P < 0.001, HF and HFY: 6.8; HS: 6.6, HSY: 6.7). However, no difference was observed in faecal pH when HSY was compared to both HF diets. Yeast had no effect on the size of the faecal particles (P > 0.05). Yeast increased in vitro gas production, suggesting more energy could be extracted from the feed, and the in vivo AD of some of the nutrients when HF and HS diets were fed.
Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time.
FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n = 69), 3 months (n = 29) and 12 months (n = 36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point.
Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed ‘enhancement’ followed by ‘coping with unpleasant affect’ and ‘social motive’ more highly for their cannabis use than any other reason. ‘Conformity and acceptance’ followed closely. ‘Relief of positive symptoms and side effects’ was the least endorsed motive.
Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated ‘enhancement’ most highly for their cannabis use.
In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear.
To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis.
Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist–hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients.
A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. β = 0.36, P = 0.01), higher leptin levels (Std. β = 0.34, P = 0.02), higher waist–hip ratio (Std. β = 0.32, P = 0.04) and lower testosterone levels (Std. β = −0.44, P = 0.002). In contrast, in females, SFQ scores were not associated with any of these factors.
While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist–hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
Healthcare-associated bloodstream infections (HABSIs) are a significant cause of mortality and morbidity in the neonatal intensive care unit (NICU) population. Our objectives were to review the epidemiology of HABSIs in our NICU and to examine the applicability of National Healthcare Safety Network (NHSN) definitions to the NICU population.
We performed a retrospective review of all neonates admitted to the 54-bed, level IV NICU at Yale-New Haven Children’s Hospital with a HABSI between January 1, 2013, and December 31, 2018. Clinical definitions per NICU team and NHSN site-specific definitions used for source identification were compared using the McNemar χ2 test.
We identified 86 HABSIs with an incidence rate of 0.80 per 1,000 patient days. Only 13% of these were CLABSIs. Both CLABSIs and non–catheter-related bloodstream infections occurred primarily in preterm neonates, but the latter were associated with a significantly higher incidence of comorbidities and the need for respiratory support. The NHSN definitions were less likely to identify a source compared to the clinical definitions agreed upon by our NICU treating team (P < .001). Furthermore, 50% of patients without an identified source of infection by NHSN definitions were bacteremic with a mucosal barrier injury organism, likely from gut translocation.
HABSIs occur primarily in premature infants with comorbidities, and CLABSIs account for a small proportion of these infections. With the increasing focus on HABSI prevention, there is a need for better NHSN site-specific definitions for the NICU population to prevent misclassification and direct prevention efforts.
We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Background: Spinal muscular atrophy (SMA) is a children’s neuromuscular disorder. Although motor neuron loss is a major feature of the disease, we have identified fatty acid abnormalities in SMA patients and in preclinical animal models, suggesting metabolic perturbation is also an important component of SMA. Methods: Biochemical, histological, proteomic, and high resolution respirometry were used. Results: SMA patients are more susceptible to dyslipidemia than the average population as determined by a standard lipid profile in a cohort of 72 pediatric patients. As well, we observed a non-alcoholic liver disease phenotype in apreclinical mouse model. Denervation alone was not sufficient to induce liver steatosis, as a mouse model of ALS, did not develop fatty liver. Hyperglucagonemia in Smn2B/-mice could explain the hepatic steatosis by increasing plasma substrate availability via glycogen depletion and peripheral lipolysis. Proteomic analysis identified mitochondrion and lipid metabolism as major clusters. Alterations in mitochondrial function were revealed by high-resolution respirometry. Finally, low-fat diets led to increased survival in Smn2B/-mice. Conclusions: These results provide strong evidence for lipid metabolism defects in SMA. Further investigation will be required to establish the primary mechanism of these alterations and understand how they lead to additional co-morbidities in SMA patients.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
The archaeological site of Al-Ashoosh is a third-millennium BC settlement
located in the Rub al-Khali Desert (or Empty Quarter), 70km south of Dubai
in the United Arab Emirates (UAE) (Figure 1). This site provides an
excellent example of the type of occupation of the inland deserts of the
Oman peninsula during the period following the Holocene Climatic Optimum.
Between November 2015 and May 2016, the Dubai Municipality and the Sanisera
Archaeology Institute conducted excavations at the site of Al-Ashoosh. This
site was discovered during two seasons of survey in 2002–2003. This survey
work, undertaken by the Dubai Municipality and the Department of Antiquities
of Jordan, identified 33 archaeological sites ranging in date from
prehistory to the late Islamic period. In 2006–2007, more-detailed
archaeological investigations of the area of Al-Ashoosh were conducted,
including survey, excavation and geological sampling (Casana et
al. 2009; Herrmann 2012; Contreras & Carcacer 2016).
Clozapine remains the only evidence-based antipsychotic for treatment-resistant schizophrenia (TRS). The ability to predict which patients with their first onset of schizophrenia would subsequently meet criteria for treatment resistance (TR) could help to diminish the severe functional disability which may ensue if TR is not recognized and correctly treated.
This is a 5-year longitudinal assessment of clinical outcomes in a cohort of 246 first-episode schizophrenia spectrum patients recruited as part of the NIHR Genetics and Psychosis (GAP) study conducted in South London from 2005 to 2010. We examined the relationship between baseline demographic and clinical measures and the emergence of TR. TR status was determined from a review of electronic case records. We assessed for associations with early-, and late-onset TR, and non-TR, and differences between those TR patients treated with clozapine and those who were not.
Seventy per cent (n = 56) of TR patients, and 23% of the total study population (n = 246) were treatment resistant from illness onset. Those who met criteria for TR during the first 5 years of illness were more likely to have an early age of first contact for psychosis (<20 years) [odds ratio (OR) 2.49, 95% confidence interval (CI) 1.25–4.94] compared to those with non-TR. The relationship between an early age of first contact (<20 years) and TR was significant in patients of Black ethnicity (OR 3.71, 95% CI 1.44–9.56); and patients of male gender (OR 3.13 95% CI 1.35–7.23).
For the majority of the TR group, antipsychotic TR is present from illness onset, necessitating increased consideration for the earlier use of clozapine.
Introduction: Point of care ultrasound (PoCUS) provides invaluable information during resuscitation efforts in cardiac arrest by determining presence/absence of cardiac activity and identifying reversible causes such as pericardial tamponade. There is no agreed guideline on how to safely and effectively incorporate PoCUS into the advanced cardiac life support (ACLS) algorithm. We consider that a consensus-based priority checklist using a “4 F’s” approach (Fluid; Form; Function; Filling), would provide a better algorithm during ACLS. Methods: The ultrasound subcommittee of the Australasian College for Emergency Medicine (ACEM) drafted a checklist incorporating PoCUS into the ACLS algorithm. This was further developed using the input of 24 international experts associated with five professional organizations led by the International Federation of Emergency Medicine. A modified Delphi tool was developed to reach an international consensus on how to integrate ultrasound into cardiac arrest algorithms for emergency department patients. Results: Consensus was reached following 3 rounds. The agreed protocol focuses on the timing of PoCUS as well as the specific clinical questions. Core cardiac windows performed during the rhythm check pause in chest compressions are the sub-xiphoid and parasternal cardiac views. Either view should be used to detect pericardial fluid, as well as examining ventricular form (e.g. right heart strain) and function, (e.g. asystole versus organized cardiac activity). Supplementary views include lung views (for absent lung sliding in pneumothorax and for pleural fluid), and IVC views for filling. Additional ultrasound applications are for endotracheal tube confirmation, proximal leg veins for DVT, or for sources of blood loss (AAA, peritoneal/pelvic fluid). Conclusion: The authors hope that this process will lead to a consensus-based SHoC-cardiac arrest guideline on incorporating PoCUS into the ACLS algorithm.
New observations of the Magellanic Stream were made in December 1976 with the 64-m radio telescope at the Parkes Observatory of CSIRO. The ridges of H I emission of the Stream were traced from near its tip at ℓ = 90°, b = -40° to the Magellanic Clouds. This was the first time that the total length of the Stream was observed with the one system (only possible from the southern hemisphere) and with high spatial (15’ of arc) and velocity (4 km s-1) resolution. The results of this survey are presented in Figures 1 and 2 and the main features are listed below.
An extensive survey of HI absorption in the spectra of discrete radio sources has been in progress for the past three years at the Parkes radio observatory. One part of the survey comprising sources along the galactic plane north of declination —50° has recently been completed. In this communication we discuss some conclusions concerning the distances of 10 sources drawn from a preliminary analysis of the data.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.