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To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438).
We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections.
Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts.
Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.
To explore the phenomenology of auditory verbal hallucinations (AVHs) in a clinical sample of young people who have a ‘non-psychotic’ diagnosis.
Ten participants aged 17–31 years with presentation of emotionally unstable personality disorder or post-traumatic stress disorder and frequent AVHs were recruited and participated in a qualitative study exploring their subjective experience of hearing voices. Photo-elicitation and ethnographic diaries were used to stimulate discussion in an otherwise unstructured walking interview.
‘Non-psychotic’ voices comprised auditory qualities such as volume and clarity. Participants commonly personified their voices, viewing them as distinct characters with which they could interact and form relationships. There appeared to be an intimate and unstable relationship between participant and voice, whereby voices changed according to the participants’ mood, insecurities, distress and circumstance. Equally, participants reacted to provocation by the voice, leading to changes in mood and circumstance through emotional and physical disturbances. In contrast to our previous qualitative work in psychosis, voice hearing was not experienced with a sense of imposition or control.
This phenomenological research yielded in-depth and novel accounts of ‘non-psychotic’ voices which were intimately linked to emotional experience. In contrast to standard reports of voices in disorders such as schizophrenia, participants described a complex and bi-directional relationship with their voices. Many other features were in common with voice hearing in psychosis. Knowledge of the phenomenology of hallucinations in non-psychotic disorders has the potential to inform future more successful management strategies. This report gives preliminary evidence for future research.
Improving the quality of care on psychiatric inpatient wards has been a major focus in recent mental health policy, a recurrent criticism being that contact between staff and patients is limited in time and therapeutic value. Change is unlikely to be achieved without recruitment and retention of a high quality and well-motivated work force.
The NHS commissioned national inpatient mental health staff morale study is intended to inform service planning and policy by delivering evidence on the morale of the inpatient mental health workforce and the clinical, organisational, architectural and human resources factors that influence it.
100 wards in 17 area ‘Trusts’ are participating in the study, in addition to 40 community teams. The study will take place over two years, and has 6 modules:
1. A quantitative questionnaire for all staff in participating wards and
2. A comparison group in 20 community mental health teams and 20 crisis teams.
3. Case studies of 10 wards scoring in the top and bottom quartile for indicators of morale.
4. Repeated questionnaires for 20 wards in the second year to investigate how morale changes over time.
5. Staff who leave the wards in the course of the first year will be asked their reasons for leaving.
6. Links between rates of staff sickness and morale will be investigated.
Questionnaires have been distributed to 3,500 staff with a response rate of 65%, results from which will be presented in 2009.
Evidence suggests that the subjective experience of AVHs cannot be explained by any of the existing cognitive models, highlighting the obvious need to properly investigate the actual, lived experience of AVHs, and derive models/theories that fit the complexity of this.
Via phenomenological interviews and ethnographic diary methods, we aim to gain a deeper insight into the experience of AVHs.
To explore the phenomenological quality of AVHs, as they happen/reveal themselves to consciousness,   without relying on existing suppositions.
Participants with First Episode Psychosis were recruited from the Birmingham Early Intervention Service (EIS), BSMHFT. In-depth 'walking interviews' were carried out with each participant, together with standardised assessment measures of voices. Prior to interviews, participants were asked to complete a dairy and take photographs, further capturing aspects of their AVH experiences.
20 participants have completed interviews to date. Emerging themes cover the form and quality of voices (i.e. as being separate to self, imposing, compelling etc.), and participants' understanding and management of these experiences.
Authentic descriptions gleaned from participants have the potential to increase our understanding of the relationship between the phenomenology and neurobiology of AVHs and, in turn, the experience as a whole.
Neurobiological models of auditory verbal hallucination (AVH) have been advanced by symptom capture functional magnetic resonance imaging (fMRI), where participants self-report hallucinations during scanning. To date, regions implicated are those involved with language, memory and emotion. However, previous studies focus on chronic schizophrenia, thus are limited by factors, such as medication use and illness duration. Studies also lack detailed phenomenological descriptions of AVHs. This study investigated the neural correlates of AVHs in patients with first episode psychosis (FEP) using symptom capture fMRI with a rich description of AVHs. We hypothesised that intrusive AVHs would be associated with dysfunctional salience network activity.
Sixteen FEP patients with frequent AVH completed four psychometrically validated tools to provide an objective measure of the nature of their AVHs. They then underwent fMRI symptom capture, utilising general linear models analysis to compare activity during AVH to the resting brain.
Symptom capture of AVH was achieved in nine patients who reported intrusive, malevolent and uncontrollable AVHs. Significant activity in the right insula and superior temporal gyrus (cluster size 141 mm3), and the left parahippocampal and lingual gyri (cluster size 121 mm3), P < 0.05 FDR corrected, were recorded during the experience of AVHs.
These results suggest salience network dysfunction (in the right insula) together with memory and language processing area activation in intrusive, malevolent AVHs in FEP. This finding concurs with others from chronic schizophrenia, suggesting these processes are intrinsic to psychosis itself and not related to length of illness or prolonged exposure to antipsychotic medication.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Unlike for many other respiratory infections, the seasonality of pertussis is not well understood. While evidence of seasonal fluctuations in pertussis incidence has been noted in some countries, there have been conflicting findings including in the context of Australia. We investigated this issue by analysing the seasonality of pertussis notifications in Australia using monthly data from January 1991 to December 2016. Data were made available for all states and territories in Australia except for the Australian Capital Territory and were stratified into age groups. Using a time-series decomposition approach, we formulated a generalised additive model where seasonality is expressed using cosinor terms to estimate the amplitude and peak timing of pertussis notifications in Australia. We also compared these characteristics across different jurisdictions and age groups. We found evidence that pertussis notifications exhibit seasonality, with peaks observed during the spring and summer months (November–January) in Australia and across different states and territories. During peak months, notifications are expected to increase by about 15% compared with the yearly average. Peak notifications for children <5 years occurred 1–2 months later than the general population, which provides support to the theory that older household members remain an important source of pertussis infection for younger children. In addition, our results provide a more comprehensive spatial picture of seasonality in Australia, a feature lacking in previous studies. Finally, our findings suggest that seasonal forcing may be useful to consider in future population transmission models of pertussis.
The use of monthly intranasal mupirocin was associated with a significant reduction in the rate of methicillin-resistant Staphylococcus aureus transmission and Staphylococcus aureus invasive infection in a large neonatal intensive care unit. Resistance to mupirocin emerged over time, but it was rare and was not associated with adverse clinical outcomes.
Cognitive reserve (CR) has been associated with better cognitive function and lower risk of depression in older people, yet it remains unclear whether CR moderates the association between mood and cognition. This study aimed to investigate whether a comprehensive indicator of CR, including education, occupation and engagement in cognitive and social activities, acts as a moderator of this association.
This was a cross-sectional study utilising baseline data from the Cognitive Function and Ageing Study II (CFAS II), a large population-based cohort of people aged 65+ in England. Complete data on the measures of CR, mood and cognition were available for 6565 dementia-free individuals. Linear regression models were used to investigate the potential modifying effect of CR on the association between cognition and mood with adjustment for age, sex and missing data.
Levels of CR did moderate the negative association between mood and cognition; the difference in cognition between those with and without a clinical level mood disorder was significantly smaller in the middle (−2.28; 95% confidence interval (CI) −3.65 to −0.90) and higher (−1.30; 95% CI −2.46 to −0.15) CR groups compared with the lower CR group (−4.01; 95% CI −5.53 to −2.49). The individual components of CR did not significantly moderate the negative association between mood and cognition.
These results demonstrate that CR, indexed by a composite score based on multiple indicators, can moderate the negative association between lowered mood and cognition, emphasising the importance of continuing to build CR across the lifespan in order to maintain cognitive health.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
Salience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.
We examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.
ARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.
Our findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.
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.
A series of research reports has indicated that the use of substances such as cannabis, alcohol and tobacco are higher in youth at clinical high risk (CHR) of developing psychosis than in controls. Little is known about the longitudinal trajectory of substance use, and findings on the relationship between substance use and later transition to psychosis in CHR individuals are mixed.
At baseline and 6- and 12-month follow-ups, 735 CHR and 278 control participants completed the Alcohol and Drug Use Scale and a cannabis use questionnaire. The longitudinal trajectory of substance use was evaluated with linear mixed models.
CHR participants endorsed significantly higher cannabis and tobacco use severity, and lower alcohol use severity, at baseline and over a 1-year period compared with controls. CHR youth had higher lifetime prevalence and frequency of cannabis, and were significantly younger upon first use, and were more likely to use alone and during the day. Baseline substance use did not differentiate participants who later transitioned to psychosis (n = 90) from those who did not transition (n = 272). Controls had lower tobacco use than CHR participants with a prodromal progression clinical outcome and lower cannabis use than those with a psychotic clinical outcome at the 2-year assessment.
In CHR individuals cannabis and tobacco use is higher than in controls and this pattern persists across 1 year. Evaluation of clinical outcome may provide additional information on the longitudinal impact of substance use that cannot be detected through evaluation of transition/non-transition to psychosis alone.
In Australia, varicella vaccine was universally funded in late 2005 as a single dose at 18 months. A school-based catch-up programme for children aged 10–13 years without a history of infection or vaccination was funded until 2015, when those eligible for universal infant vaccination would have reached the age of high school entry. This study projects the impact of discontinuing catch-up vaccination on varicella and zoster incidence and morbidity using a transmission dynamic model, in comparison with alternative policy options, including two-dose strategies. At current vaccine coverage (83% at 2 years and 90% at 5 years), ceasing the adolescent catch-up programme in 2015 was projected to increase varicella-associated morbidity between 2035 and 2050 by 39%. Although two-dose infant programmes had the lowest estimated varicella morbidity, the incremental benefit from the second dose fell by 70% if first dose coverage increased from 83% to 95% by age 24 months. Overall zoster morbidity was predicted to rise after vaccination, but differences between strategies were small. Our results suggest that feasibility of one-dose coverage approaching 95% is an important consideration in estimating incremental benefit from a second dose of varicella vaccine.
We present near-infrared spectro-interferometric studies of red supergiant (RSG) stars using the VLTI/AMBER instrument, which are compared to previously obtained similar observations of AGB stars. Our observations indicate spatially extended atmospheric molecular layers of water vapor and CO, similar as previously observed for Mira stars. Data of VY~CMa indicate that the molecular layers are asymmetric, possibly clumpy. Thanks to the spectro-interferometric capabilities of the VLTI/AMBER instrument, we can isolate continuum bandpasses, estimate fundamental parameters of our sources, locate them in the HR diagram, and compare their positions to recent evolutionary tracks. For the example of VY CMa, this puts it close to evolutionary tracks of initial mass 25-32 M⊙. Comparisons of our data to hydrostatic model atmospheres, 3d simulations of convection, and 1d dynamic model atmospheres based on self-excited pulsation models indicate that none of these models can presently explain the observed atmospheric extensions for RSGs. The mechanism that levitates the atmospheres of red supergiant is thus a currently unsolved problem.
Despite their pivotal role as primary producers, there is little information as to the diversity and physiology of cyanobacteria in the meltwater ecosystems of polar regions. Thirty cyanobacterial mats from Adelaide Island, Antarctica were investigated using 16S rRNA gene pyrosequencing and automated ribosomal intergenic spacer analysis, and screened for cyanobacterial toxins using molecular and chemical approaches. A total of 274 operational taxonomic units (OTUs) were detected. The richness ranged between 8 and 33 cyanobacterial OTUs per sample, reflecting a high mat diversity. Leptolyngbya and Phormidium (c. 55% and 37% of the OTUs per mat) were dominant. Cyanobacterial community composition was similar between mats, particularly those obtained from closely adjacent locations. The cyanotoxin microcystin was detected in 26 of 27 mats (10–300 ng g-1 organic mass), while cylindrospermopsin, detected for the first time in Antarctica, was present in 21 of 30 mats (2–156 ng g-1 organic mass). The latter was confirmed via liquid chromatography-mass spectrometry and by the presence of the cyrAB and cyrJ genes. This study demonstrates the usefulness of pyrosequencing for characterizing diverse cyanobacterial communities, and confirms that cyanobacteria from extreme environments produce a similar range of cyanotoxins as their temperate counterparts.