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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.
Voters evaluate politicians not just by what they say, but also how they say it, via facial displays of emotions and vocal pitch. Candidate characteristics can shape how leaders use—and how voters react to—nonverbal cues. Drawing on role congruity expectations, we study how the use of and reactions to facial, vocal, and textual communication in political debates varies by candidate gender. Relying on full-length videos of four German federal election debates (2005–2017) and a minor party debate, we use video, audio, and text data to measure candidate facial displays of emotion, vocal pitch, and speech sentiment. Consistent with our expectations, Angela Merkel expresses less anger than her male opponents, but she is just as emotive in other respects. Combining these measures of emotional expression with continuous responses recorded by live audiences, we find that voters punish Merkel for anger displays and reward her happiness and general emotional displays.
Traversodontidae is a group of Triassic herbivorous/omnivorous cynodonts that represents the most diversified lineage within Cynognathia. In southern Brazil, a rich fossil record of late Middle/mid-Late Triassic cynodonts has been documented, with Exaeretodon riograndensis Abdala, Barberena, and Dornelles, 2002 and Siriusgnathus niemeyerorum Pavanatto et al., 2018 representing two abundant and well-documented traversodontids. The present study provides a comparative analysis of the morphology of the nasal cavity, nasal recesses, nasolacrimal duct, and maxillary canals of both species using computed tomography, highlighting the changes that occurred in parallel to the origin of mammaliaforms. Our results show that there were no ossified turbinals or a cribriform plate delimiting the posterior end of the nasal cavity, suggesting these structures were probably cartilaginous as in nonmammaliaform cynodonts. Both species show lateral ridges on the internal surface of the roof of the nasal cavity, but the median ridge for the attachment of a nasal septum is absent. Exaeretodon riograndensis and S. niemeyerorum show recesses on the dorsal region of the nasal cavity, which increase the volume of the nasal cavity, potentially enhancing the olfactory chamber and contributing to the sense of smell. On the lateral sides of the nasal cavity, the analyzed taxa show a well-developed maxillary recess. Although E. riograndensis and S. niemeyerorum have roughly similar nasal cavities, in the former taxon, the space between the left and right dorsal recesses of the nasal cavity is uniform along its entire extension, whereas this space narrows posteriorly in S. niemeyerorum. Finally, the nasolacrimal duct of S. niemeyerorum is more inclined anteroposteriorly than in E. riograndensis.
Wildlife reintroduction projects often face resistance from local residents who see potential conflicts with the species or lack trust or confidence in the agencies and professionals involved in reintroduction. Yet the linkages between trust, confidence, risk perceptions, attitudes towards the species and local support for its reintroduction are not well known. The Dual-Mode Model of Cooperation and Cognitive Hierarchy Model were theoretical frameworks used to shed light on these linkages by exploring the potential roles trust and confidence play as mediators between risk perceptions and attitudes towards, and support for, reintroduced elk in Tennessee (USA). A mail survey of 1005 residents living in the five-county area surrounding the North Cumberland Elk Restoration Zone assessed resident attitudes and risk perceptions towards the reintroduced elk, trust towards the managing wildlife agency and support for continued conservation efforts. A structural equation model revealed that trust and confidence play positive roles in mitigating risk perceptions and improving support for the reintroduction of elk. The findings confirm the roles public trust and confidence play in wildlife reintroductions and should help agencies work towards building local trust and confidence, minimizing risks, improving attitudes and increasing the chances for successful outcomes for the species and people.
Very few zircon-bearing, kimberlite-hosted mantle eclogite xenoliths have been identified to date; however, the zircon they contain is crucial for our understanding of subcratonic lithospheric mantle evolution and eclogite genesis. In this study, we constrain the characteristics of zircon from mantle eclogite xenoliths based on existing mineralogical and geochemical data from zircons from different geological settings, and on the inferred origin of mantle eclogites. Given the likely origin and subsequent evolution of mantle eclogites, we infer that the xenoliths can contain zircons with magmatic, metamorphic and xenogenic (i.e. kimberlitic zircon) origins. Magmatic zircon can be inherited from low-pressure mafic oceanic crust precursors, or might form during direct crystallization of eclogites from primary mantle-derived melts at mantle pressures. Metamorphic zircon within mantle eclogites has a number of possible origins, ranging from low-pressure hydrothermal alteration of oceanic crustal protoliths to metasomatism related to kimberlite magmatism. This study outlines a possible approach for the identification of inherited magmatic zircon within subduction-related mantle eclogites as well as xenogenic kimberlitic zircon within all types of mantle eclogites. We demonstrate this approach using zircon grains from kimberlite-hosted eclogite xenoliths from the Kasai Craton, which reveals that most, if not all, of these zircons were most likely incorporated as a result of laboratory-based contamination.
In Brazil, the buffalo milk market has been growing. However, identity and quality standards have not been established for this raw material, nor have proper distinctions between buffalo milk and bovine milk been defined. Currently, the State of Rio Grande do Sul (RS) has only three producers that supply raw material for officially marketed derivatives. The aim of this study was to determine the identity and quality standards of raw buffalo milk in this region. Samples were obtained biweekly from three farm cooling tanks between June 2017 and August 2018, to reach a total of 69 samples. The averages for the results of the physicochemical parameters fat, protein, lactose, total solids, SNF (solids-not-fat), calcium, density, FP, acidity and SCC were 5.5 g/100 g, 4.06 g/100 g, 5.07 g/100 g, 15.5 g/100 g, 9.96 g/100 g, 0.161 g/100 g, 1.034 g/ml, −0.527°C, 16°D and 95 × 103 cells/ml, respectively. With reference to the microbiological parameters, the mean of the Standard Plate Count (SPC) and thermotolerant coliforms were 9,0 × 104 CFU/ml and 1.6 × 102 MPN/ml, respectively. Regarding coagulase-positive staphylococci, 36 samples tested positive (52% of total). Neither Salmonella spp. nor Listeria monocytogenes, nor antibiotic or antiparasitic residues were detected in any sample. In conclusion, the buffalo milk used as raw material for dairy products in southern Brazil demonstrated satisfactory physicochemical and microbiological characteristics, in accordance with recent scientific literature.
Cognitive behavioural therapy (CBT) is an important treatment in conjunction with psychopharmacotherapy in schizophrenia. However, there is only very little research on the effects of such interventions on brain function.
Recent studies have suggested that jumping to conclusions and a specific attributional bias is a predominant cognitive style in patients which might lead to the development of delusions. In this multi-centre fMRI trial, we investigated the effect of nine months of CBT on neural correlates of “jumping to conclusions” and the “attributional style” in patients with psychosis. Eighty patients and 80 control subjects were recruited in six centres and measured with 3-Tesla functional magnetic imaging (fMRI) before and after CBT.
It could be shown that CBT ameliorates differences in brain activations between patients and controls after nine months.
These results support the feasibility of fMRI multicenter trials and sheds further light into the mechanisms relating psychotherapy to brain function in Schizophrenia.
We report on the case of a patient who developed an acute meningitis and, after a period of about two weeks, without any neuropsychiatric problems, an acute paranoid-hallucinatory and catatonic syndrome. The symptomatology is discussed, in relation with the diagnostic difficulties of differentiating between a biphasic meningo-encephalitis with an organic psychosis or a first manifestation of an endogenous psychosis.
In the treatment of MDD, insufficient treatment outcome and the delayed onset of action still remain major problems.
Measuring plasma concentrations, i.e. TDM is a possible option to improve therapeutic outcomes.
The aim of this prospective and naturalistic study was to evaluate the economic and clinical benefit of TDM for depressed inpatients treated with citalopram.
Inpatients with MDD according to ICD-10 were included and treated with citalopram. Psychopathology was assessed by the 17-item Hamilton Depression (HAMD-17) rating scale in weekly intervals for five weeks. In parallel, serum concentrations of citalopram were measured.
55 patients were included (27f). 84% of the patients with citalopram plasma concentrations below 50 ng/ml (n = 36) were non-responders in week five. Among patients who achieved plasma concentrations ≥50 ng/ml (n = 19) on day 7, 47% became responder at week five (p = 0.025). Patients with plasma levels ≥50 ng/ml had a significantly shorter duration of hospitalization (49 ± 20) than patients below 50 ng/ml (72 ± 37; p = 0.033).
Our results show that citalopram plasma levels above 50 ng/ml are predictive for later treatment outcome and that TDM is cost effective due to reduced duration of hospitalization.
The influence of repetitive transcranial magnetic stimulation (rTMS) on mood in healthy people is uncertain, as former studies show divergent results. Previous studies in healthy volunteers focused exclusively on the immediate effect of a single session of rTMS on mood.
The aim of this study was to analyse the influence on mood of a series of 9 High Frequency (HF) rTMS stimulations of the left dorsolateral prefrontal cortex (DLPFC).
44 young healthy male volunteers were randomly assigned to receive 9 sessions of active HF-rTMS (n = 22) or sham rTMS (n = 22) over the left DLPFC. Each session in the active group consisted of 15 trains of 25 Hz starting with 100% of motor threshold. Sham stimulation was performed following the same protocol, but using a sham coil. The variables of interest were the Beck Depression Inventory (BDI) and Visual Analogue Scales (VAS) which quantified “mood”, “enjoyment” and “energy”.
We found a significant reduction of the BDI score in the active group (GLM, p < 0.001) whereas no significant changes of the BDI score were caused by sham stimulation (GLM, p = 0.109). We did not find significant differences caused by active or sham stimulation in VAS scales except for the VAS labelled lively/gloomy immediately after stimulation. The active group was found to be more “gloomy” (p = 0.001).
Our data support the hypothesis that a 9-day long series of HF-rTMS of the left DLPFC improves mood, analysed by BDI in healthy young men.
There is evidence that patients with persecutory delusions tend to attribute excessively hypothetical positive events to internal causes and hypothetical negative events to external causes, arrive at hasty conclusions and fail in gathering and assessing adequate feedback, particularly when emotionally salient material is involved. Research on the neural correlates of the corresponding neural correlates and even more so on the potential effects of cognitive behavioral therapy (CBT) on the associated cerebral networks is almost unavailable.
The first and preliminary results of a multicentre fMRI study will be presented.
In this study eighty schizophrenia patients from the POSITIVE clinical trial and eighty healthy subjects were recruited at six German university hospitals (Bonn, Duisburg-Essen, Düsseldorf, Frankfurt, Cologne, Tubingen). After nine months of therapy (either with CBT or Supportive Therapy) patients and controls were re-examined enabling the study correlates of cerebral reorganization processes.
We found reliable differences in brain activation relating to phenomena of decision making under uncertainty, and biased attribution (self- vs. external reference of emotional events).
The comparison of both groups revealed significant decreased activation in key areas for decision making, self-reflection, self-relevance and agency attribution of patients with schizophrenia.
The preliminary data analysis of the still blinded treatment arms shows significantly increased activations in these areas after nine months of CBT. This suggest neuroplasitic changes according to relearning strategies in psychotic patients with schizophrenia and will hopefully give rise to a more widespread application of CBT in treatment of schizophrenia.
26.5% of psychiatric patients in Germany have minor children. More than half of these children have specific needs, which are seldom met.
To examine problems, needs and used interventions for families with a mentally ill parent in the federal state of Saxony, Germany. The study focused on outpatients and included mothers and fathers and all psychiatric disorders.
We asked all psychiatrists in the federal state of Saxony to take part in our study. All patients with minor children who came to one of the 58 participating psychiatrist's practices at an appointed date were asked to fill out a detailed questionnaire including sociodemographic data, the Strengths and Difficulties Questionnaire (SDQ), specific needs, used interventions and reasons for not using interventions. The questionnaire was developed using data from 26 expert interviews.
128 psychiatric outpatients took part in our study (78% female). The most common diagnoses were depression and anxiety disorders. More than 40% of the patients rated their children in the SDQ in an abnormal or borderline range. 22% of the children have been treated because of emotional or behavioural problems. Reasons not to use interventions were missing knowledge and fear of stigmatisation.
HELP-S for children is the first study which examines the situation of children with a mentally ill parent in an outpatient setting. Therefore, our results are an improvement in research in the field of families with a mentally ill parent and heading towards the improvement of care.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility.
Fifty-one non-clinical volunteers (33 women) completed state and trait anxiety questionnaire measures, were assessed with a clinical examination for hypermobility (Beighton system) and performed an emotional face processing paradigm during functional neuroimaging.
Trait anxiety scores did significantly correlate with both state anxiety and hypermobility scores. BOLD signals of the hippocampus did positively correlate with hypermobility scores for the crying faces versus neutral faces contrast in ROI analyses. No results were found for any of the other studied ROIs. Additionally, hypermobility scores were also associated with other key affective processing areas (i.e. the middle and anterior cingulate gyrus, fusiform gyrus, parahippocampal region, orbitofrontal cortex and cerebellum) in the whole brain analysis.
Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arises in this population.