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In an empirical study on the classification of the psychoses, 302 patients were rated using the Longitudinal Psychopathology Schedule. The data were condensed by factor analysis, which yielded 10 factors - mania and schizomania, depression and suicidal activity, and 6 factors concerned with psychotic symptoms (verbal hallucinosis/passivity, delusion formation, defect symptoms, social decline, cycloid symptomatology and a factor loading depressive auditory hallucinations and visual hallucinations). Provisional diagnostic groups were obtained using DSM III. Discriminant function analyses showed that the only clearly distinct diagnostic group was bipolar disorder, and this was true for various definitions. Canonical variate analyses were performed using 3- and 4-criterion groups. These showed that a group corresponding approximately to cycloid psychosis also met criteria for being a distinct group. The most detailed examination pf the data, using 4-criterion groups and serial reclassification, suggested that the psychoses might fall into 5 groups - bipolar disorder, cycloid psychosis, depression, defect states and schizoaffective depression.
Situated in the southwest, bounded by mountains and watered by the Yangzi and several tributaries, the region occupied by the former Warring States-period state of Shu was secure and rich in both agricultural and mineral resources. An abundant supply of copper and tin had led to the rise of a bronze-producing society at Sanxingdui, contemporary with the Shang at Anyang (c.1200 bce), and later, salt, iron, and natural-gas deposits were developed into thriving industries during the late Zhou period. Moreover, quality soil, easy access to water, and a warm and lengthy growing season made the region highly productive in terms of agriculture. After Shu was conquered by Qin in the third century bce, a large number of families from the Central Plains were relocated to the area to provide material support for the Qin war effort. It was due in no small measure to the resources extracted from Shu that Qin was able to conquer and unify China by 221 bce.
Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).
To compare the switch between the TCA nortriptyline and the SSRI escitalopram.
Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.
Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.
These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.
Declarations of interest
K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.
This paper reviews recent research into predicting the eating qualities of beef. A range of instrumental and grading approaches have been discussed, highlighting implications for the European beef industry. Studies incorporating a number of instrumental and spectroscopic techniques illustrate the potential for online systems to non-destructively measure muscle pH, colour, fat and moisture content of beef with R2 (coefficient of determination) values >0.90. Direct predictions of eating quality (tenderness, flavour, juiciness) and fatty acid content using these methods are also discussed though success is greatly variable. R2 values for instrumental measures of tenderness have been quoted as high as 0.85 though R2 values for sensory tenderness values can be as low as 0.01. Discriminant analysis models can improve prediction of variables such as pH and shear force, correctly classifying beef samples into categorical groups with >90% accuracy. Prediction of beef flavour continues to challenge researchers and the industry alike, with R2 values rarely quoted above 0.50, regardless of instrumental or statistical analysis used. Beef grading systems such as EUROP and United States Department of Agriculture systems provide carcase classification and some indication of yield. Other systems attempt to classify the whole carcase according to expected eating quality. These are being supplemented by schemes such as Meat Standards Australia (MSA), based on consumer satisfaction for individual cuts. In Australia, MSA has grown steadily since its inception generating a 10% premium for the beef industry in 2015-16 of $187 million. There is evidence that European consumers would respond to an eating quality guarantee provided it is simple and independently controlled. A European beef quality assurance system might encompass environmental and nutritional measures as well as eating quality and would need to be profitable, simple, effective and sufficiently flexible to allow companies to develop their own brands.
The Meat Standards Australia (MSA) grading scheme has the ability to predict beef eating quality for each ‘cut×cooking method combination’ from animal and carcass traits such as sex, age, breed, marbling, hot carcass weight and fatness, ageing time, etc. Following MSA testing protocols, a total of 22 different muscles, cooked by four different cooking methods and to three different degrees of doneness, were tasted by over 19 000 consumers from Northern Ireland, Poland, Ireland, France and Australia. Consumers scored the sensory characteristics (tenderness, flavor liking, juiciness and overall liking) and then allocated samples to one of four quality grades: unsatisfactory, good-every-day, better-than-every-day and premium. We observed that 26% of the beef was unsatisfactory. As previously reported, 68% of samples were allocated to the correct quality grades using the MSA grading scheme. Furthermore, only 7% of the beef unsatisfactory to consumers was misclassified as acceptable. Overall, we concluded that an MSA-like grading scheme could be used to predict beef eating quality and hence underpin commercial brands or labels in a number of European countries, and possibly the whole of Europe. In addition, such an eating quality guarantee system may allow the implementation of an MSA genetic index to improve eating quality through genetics as well as through management. Finally, such an eating quality guarantee system is likely to generate economic benefits to be shared along the beef supply chain from farmers to retailors, as consumers are willing to pay more for a better quality product.
Accurately quantifying a consumer’s willingness to pay (WTP) for beef of different eating qualities is intrinsically linked to the development of eating-quality-based meat grading systems, and therefore the delivery of consistent, quality beef to the consumer. Following Australian MSA (Meat Standards Australia) testing protocols, over 19 000 consumers from Northern Ireland, Poland, Ireland, France and Australia were asked to detail their willingness to pay for beef from one of four categories that best described the sample; unsatisfactory, good-every-day, better-than-every-day or premium quality. These figures were subsequently converted to a proportion relative to the good-every-day category (P-WTP) to allow comparison between different currencies and time periods. Consumers also answered a short demographic questionnaire. Consumer P-WTP was found to be remarkably consistent between different demographic groups. After quality grade, by far the greatest influence on P-WTP was country of origin. This difference was unable to be explained by the other demographic factors examined in this study, such as occupation, gender, frequency of consumption and the importance of beef in the diet. Therefore, we can conclude that the P-WTP for beef is highly transferrable between different consumer groups, but not countries.
The most important factors known to influence the eating quality of beef are well established and include both pre- and post-slaughter events with many of the determinants interacting with each other. A substantial programme of work has been conducted by the Agri-Food and Biosciences Institute in Northern Ireland aimed at quantifying those factors of most importance to the local beef industry. Post-slaughter effects such as carcase chilling and electrical stimulation, ageing, carcase hanging and cooking method have been shown to have a significant impact on eating quality when compared with pre-slaughter activities such as animal handling and lairage time in the Northern Ireland studies. However, the effect of animal breed, particularly the use of dairy breed animals, was shown to significantly improve eating quality. Many of these factors were found to interact with each other.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
To achieve their conservation goals individuals, communities and organizations need to acquire a diversity of skills, knowledge and information (i.e. capacity). Despite current efforts to build and maintain appropriate levels of conservation capacity, it has been recognized that there will need to be a significant scaling-up of these activities in sub-Saharan Africa. This is because of the rapid increase in the number and extent of environmental problems in the region. We present a range of socio-economic contexts relevant to four key areas of African conservation capacity building: protected area management, community engagement, effective leadership, and professional e-learning. Under these core themes, 39 specific recommendations are presented. These were derived from multi-stakeholder workshop discussions at an international conference held in Nairobi, Kenya, in 2015. At the meeting 185 delegates (practitioners, scientists, community groups and government agencies) represented 105 organizations from 24 African nations and eight non-African nations. The 39 recommendations constituted six broad types of suggested action: (1) the development of new methods, (2) the provision of capacity building resources (e.g. information or data), (3) the communication of ideas or examples of successful initiatives, (4) the implementation of new research or gap analyses, (5) the establishment of new structures within and between organizations, and (6) the development of new partnerships. A number of cross-cutting issues also emerged from the discussions: the need for a greater sense of urgency in developing capacity building activities; the need to develop novel capacity building methodologies; and the need to move away from one-size-fits-all approaches.
The chemical composition of soil from the Glasgow (UK) urban area was used to identify the controls on the availability of potentially harmful elements (PHEs) in soil to humans. Total and bioaccessible concentrations of arsenic (As), chromium (Cr) and lead (Pb) in 27 soil samples, collected from different land uses, were coupled to information on their solid-phase partitioning derived from sequential extraction data. The total element concentrations in the soils were in the range <0.1–135mgkg–1 for As; 65–3680mgkg–1 for Cr and 126–2160mgkg–1 for Pb, with bioaccessible concentrations averaging 27, 5 and 27% of the total values, respectively. Land use does not appear to be a predictor of contamination; however, the history of the contamination is critically important. The Chemometric Identification of Substrates and Element Distribution (CISED) sequential chemical extraction and associated self-modelling mixture resolution analysis identified three sample groupings and 16 geochemically distinct phases (substrates). These were related to iron (n=3), aluminium–silicon (Al–Si; n=2), calcium (n=3), phosphorus (n=1), magnesium (Mg; n=3), manganese (n=1) and easily extractable (n=3), which was predominantly made up of sodium and sulphur. As, Cr and Pb were respectively found in 9, 10 and 12 of the identified phases, with bioaccessible As predominantly associated with easily extractable phases, bioaccessible Cr with the Mg-dominated phases and bioaccessible Pb with both the Mg-dominated and Al–Si phases. Using a combination of the Unified Barge Method to measure the bioaccessibility of PHEs and CISED to identify the geochemical sources has allowed a much better understanding of the complexity of PHE mobility in the Glasgow urban environment. This approach can be applied to other urban environments and cases of soil contamination, and made part of land-use planning.
The beef industry must become more responsive to the changing market place and consumer demands. An essential part of this is quantifying a consumer’s perception of the eating quality of beef and their willingness to pay for that quality, across a broad range of demographics. Over 19 000 consumers from Northern Ireland, Poland, Ireland and France each tasted seven beef samples and scored them for tenderness, juiciness, flavour liking and overall liking. These scores were weighted and combined to create a fifth score, termed the Meat Quality 4 score (MQ4) (0.3×tenderness, 0.1×juiciness, 0.3×flavour liking and 0.3×overall liking). They also allocated the beef samples into one of four quality grades that best described the sample; unsatisfactory, good-every-day, better-than-every-day or premium. After the completion of the tasting panel, consumers were then asked to detail, in their own currency, their willingness to pay for these four categories which was subsequently converted to a proportion relative to the good-every-day category (P-WTP). Consumers also answered a short demographic questionnaire. The four sensory scores, the MQ4 score and the P-WTP were analysed separately, as dependant variables in linear mixed effects models. The answers from the demographic questionnaire were included in the model as fixed effects. Overall, there were only small differences in consumer scores and P-WTP between demographic groups. Consumers who preferred their beef cooked medium or well-done scored beef higher, except in Poland, where the opposite trend was found. This may be because Polish consumers were more likely to prefer their beef cooked well-done, but samples were cooked medium for this group. There was a small positive relationship with the importance of beef in the diet, increasing sensory scores by about 4% in Poland and Northern Ireland. Men also scored beef about 2% higher than women for most sensory scores in most countries. In most countries, consumers were willing to pay between 150 and 200% more for premium beef, and there was a 50% penalty in value for unsatisfactory beef. After quality grade, by far the greatest influence on P-WTP was country of origin. Consumer age also had a small negative relationship with P-WTP. The results indicate that a single quality score could reliably describe the eating quality experienced by all consumers. In addition, if reliable quality information is delivered to consumers they will pay more for better quality beef, which would add value to the beef industry and encourage improvements in quality.
Quantifying consumer responses to beef across a broad range of demographics, nationalities and cooking methods is vitally important for any system evaluating beef eating quality. On the basis of previous work, it was expected that consumer scores would be highly accurate in determining quality grades for beef, thereby providing evidence that such a technique could be used to form the basis of and eating quality grading system for beef. Following the Australian MSA (Meat Standards Australia) testing protocols, over 19 000 consumers from Northern Ireland, Poland, Ireland, France and Australia tasted cooked beef samples, then allocated them to a quality grade; unsatisfactory, good-every-day, better-than-every-day and premium. The consumers also scored beef samples for tenderness, juiciness, flavour-liking and overall-liking. The beef was sourced from all countries involved in the study and cooked by four different cooking methods and to three different degrees of doneness, with each experimental group in the study consisting of a single cooking doneness within a cooking method for each country. For each experimental group, and for the data set as a whole, a linear discriminant function was calculated, using the four sensory scores which were used to predict the quality grade. This process was repeated using two conglomerate scores which are derived from weighting and combining the consumer sensory scores for tenderness, juiciness, flavour-liking and overall-liking, the original meat quality 4 score (oMQ4) (0.4, 0.1, 0.2, 0.3) and current meat quality 4 score (cMQ4) (0.3, 0.1, 0.3, 0.3). From the results of these analyses, the optimal weightings of the sensory scores to generate an ‘ideal meat quality 4 score (MQ4)’ for each country were calculated, and the MQ4 values that reflected the boundaries between the four quality grades were determined. The oMQ4 weightings were far more accurate in categorising European meat samples than the cMQ4 weightings, highlighting that tenderness is more important than flavour to the consumer when determining quality. The accuracy of the discriminant analysis to predict the consumer scored quality grades was similar across all consumer groups, 68%, and similar to previously reported values. These results demonstrate that this technique, as used in the MSA system, could be used to predict consumer assessment of beef eating quality and therefore to underpin a commercial eating quality guarantee for all European consumers.
Silymarin is an extract from the plant milk thistle that was shown to have antioxidant and hyperprolactinemic properties. Taking into account the essential role of prolactin for lactating sows and the systemic oxidative stress occurring during lactation, it is of interest to investigate the potential beneficial effects of silymarin on lactating sows. A study was therefore carried out to determine the effects of providing either 1 or 8 g/day of the plant extract silymarin to lactating sows. Sows in first, second or third parity were fed conventional diets during gestation and, at farrowing, were assigned as controls (CTL, n=33), or were fed 1 g/day (SYL1, n=33) or 8 g/day (SYL8, n=33) of silymarin. The silymarin was provided in two equal amounts per day, and was fed throughout a 20-day lactation. The performance of sows and their litters was assessed and circulating concentrations of prolactin (days 7 and 18), urea (days 7 and 18) and oxidative status, via protein carbonyls and superoxide dismutase activity (day 18), were measured in sows. Milk samples were obtained on day 18 to measure standard composition. There was no effect of silymarin (P>0.10) on circulating prolactin or urea, or on oxidative damage to proteins or antioxidant potential in sows. Lactation feed intake, backfat and BW of sows were unaffected by treatment (P>0.10) as was the case for milk composition and piglet growth (P>0.10). Results demonstrate that providing up to 8 g/day of the plant extract silymarin to lactating sows had no beneficial effects in terms of circulating prolactin concentrations or oxidative status of sows, or in terms of performances of sows and their litters.
Background: Trigeminal neuralgia (TGN) is usually caused by arterial compression of the trigeminal nerve. There are very few cases caused by intra-axial brainstem masses. Little information is therefore available regarding the response to incomplete resection of offending lesions. We present one such case, and systematically review the published in the literature. Methods: Case report and systematic review of MEDLINE and EMBASE Results: Case report: A seven year-old girl is referred with typical TGN pain. MRI revealed a cervicomedullary tumor with no abnormalities of the pons or trigeminal nerve. Subtotal resection under neurophysiologic monitoring was achieved, leaving a small residual attached near the expected location of the trigeminal spinal nucleus and tract.Patient recovered well with resolution of her TGN pain. She is asymptomatic seven years post-operatively. Literature Review: We found no other published cases in children or secondary to gliomas. Among reviewed cases, only two underwent surgery. Both were adults with brainstem cavernomas and both reported substantial improvement despite incomplete resection. Conclusions: Our case as well as literature review both show that surgical resection is beneficial in such cases and, even if subtotal, can result in substantial pain relief. This suggests intra-axial compression of the trigeminal spinal nucleus and tract as the possible cause of TGN pain in such cases.
European conformation and fat grades are a major factor determining carcass value throughout Europe. The relationships between these scores and sensory scores were investigated. A total of 3786 French, Polish and Irish consumers evaluated steaks, grilled to a medium doneness, according to protocols of the ‘Meat Standards Australia’ system, from 18 muscles representing 455 local, commercial cattle from commercial abattoirs. A mixed linear effects model was used for the analysis. There was a negative relationship between juiciness and European conformation score. For the other sensory scores, a maximum of three muscles out of a possible 18 demonstrated negative effects of conformation score on sensory scores. There was a positive effect of European fat score on three individual muscles. However, this was accounted for by marbling score. Thus, while the European carcass classification system may indicate yield, it has no consistent relationship with sensory scores at a carcass level that is suitable for use in a commercial system. The industry should consider using an additional system related to eating quality to aid in the determination of the monetary value of carcasses, rewarding eating quality in addition to yield.
Delivering beef of consistent quality to the consumer is vital for consumer satisfaction and will help to ensure demand and therefore profitability within the beef industry. In Australia, this is being tackled with Meat Standards Australia (MSA), which uses carcass traits and processing factors to deliver an individual eating quality guarantee to the consumer for 135 different ‘cut by cooking methods’ from each carcass. The carcass traits used in the MSA model, such as ossification score, carcass weight and marbling explain the majority of the differences between breeds and sexes. Therefore, it was expected that the model would predict with eating quality of bulls and dairy breeds with good accuracy. In total, 8128 muscle samples from 482 carcasses from France, Poland, Ireland and Northern Ireland were MSA graded at slaughter then evaluated for tenderness, juiciness, flavour liking and overall liking by untrained consumers, according to MSA protocols. The scores were weighted (0.3, 0.1, 0.3, 0.3) and combined to form a global eating quality (meat quality (MQ4)) score. The carcasses were grouped into one of the three breed categories: beef breeds, dairy breeds and crosses. The difference between the actual and the MSA-predicted MQ4 scores were analysed using a linear mixed effects model including fixed effects for carcass hang method, cook type, muscle type, sex, country, breed category and postmortem ageing period, and random terms for animal identification, consumer country and kill group. Bulls had lower MQ4 scores than steers and females and were predicted less accurately by the MSA model. Beef breeds had lower eating quality scores than dairy breeds and crosses for five out of the 16 muscles tested. Beef breeds were also over predicted in comparison with the cross and dairy breeds for six out of the 16 muscles tested. Therefore, even after accounting for differences in carcass traits, bulls still differ in eating quality when compared with females and steers. Breed also influenced eating quality beyond differences in carcass traits. However, in this case, it was only for certain muscles. This should be taken into account when estimating the eating quality of meat. In addition, the coefficients used by the Australian MSA model for some muscles, marbling score and ultimate pH do not exactly reflect the influence of these factors on eating quality in this data set, and if this system was to be applied to Europe then the coefficients for these muscles and covariates would need further investigation.
Ossification score and animal age are both used as proxies for maturity-related collagen crosslinking and consequently decreases in beef tenderness. Ossification score is strongly influenced by the hormonal status of the animal and may therefore better reflect physiological maturity and consequently eating quality. As part of a broader cross-European study, local consumers scored 18 different muscle types cooked in three ways from 482 carcasses with ages ranging from 590 to 6135 days and ossification scores ranging from 110 to 590. The data were studied across three different maturity ranges; the complete range of maturities, a lesser range and a more mature range. The lesser maturity group consisted of carcasses having either an ossification score of 200 or less or an age of 987 days or less with the remainder in the greater maturity group. The three different maturity ranges were analysed separately with a linear mixed effects model. Across all the data, and for the greater maturity group, animal age had a greater magnitude of effect on eating quality than ossification score. This is likely due to a loss of sensitivity in mature carcasses where ossification approached and even reached the maximum value. In contrast, age had no relationship with eating quality for the lesser maturity group, leaving ossification score as the more appropriate measure. Therefore ossification score is more appropriate for most commercial beef carcasses, however it is inadequate for carcasses with greater maturity such as cull cows. Both measures may therefore be required in models to predict eating quality over populations with a wide range in maturity.
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
The RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
PRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
CT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism contributes to the development of depression (major depressive disorder, MDD), but it is unclear whether neural effects observed in healthy individuals are sustained in MDD.
To investigate BDNF Val66Met effects on key regions in MDD neurocircuitry: amygdala, anterior cingulate, middle frontal and orbitofrontal regions.
Magnetic resonance imaging scans were acquired in 79 persons with MDD (mean age 49 years) and 74 healthy volunteers (mean age 50 years). Effects on surface area and cortical thickness were examined with multiple comparison correction.
People who were Met allele carriers showed reduced caudal middle frontal thickness in both study groups. Significant interaction effects were found in the anterior cingulate and rostral middle frontal regions, in which participants in the MDD group who were Met carriers showed the greatest reduction in surface area.
Modulatory effects of the BDNF Val66Met polymorphism on distinct subregions in the prefrontal cortex in MDD support the neurotrophin model of depression.