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Clinical and Translational Science Award (CTSA) TL1 trainees and KL2 scholars were surveyed to determine the immediate impact of the COVID-19 pandemic on training and career development. The most negative impact was lack of access to research facilities, clinics, and human subjects, plus for KL2 scholars lack of access to team members and need for homeschooling. TL1 trainees reported having more time to think and write. Common strategies to maintain research productivity involved time management, virtual connections with colleagues, and shifting to research activities not requiring laboratory/clinic settings. Strategies for mitigating the impact of the COVID-19 pandemic on training and career development are described.
Abnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis.
Hundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects.
We refined Chiavaras’ classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor.
Our results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.
Velocardiofacial syndrome (VCFS) is a common genetic disorder due to a micro deletion on chromosome 22q11. This region includes several risk-associated genetic variants, including COMT, and VCFS is associated with a substantially increased risk for schizophrenia. As such, VCFS may serve as a valuable model for clarifying the neuroanatomical changes associated with genetic risk for psychosis.
A systematic literature search was conducted. Studies were included if they presented original data and were published by March 2008, compared subjects with VCFS and healthy controls and reported measures of brain regions according to SI units as mean and standard deviation. Data extracted from the studies included diagnosis, demographic variables and IQ. Statistical analysis was conducted using STATA 8.0 supplemented by ‘Metan’ software.
Twenty studies were retrieved. All measures were expressed in volumes apart from the corpus callosum (area). Subjects with VCFS showed reduced total brain volume (N=156 versus N=138), ([ES]=1.04, 95% CI:1.40, -0.67), with no significant heterogeneity or publication bias. This reduction was reflected in total hemisphere grey and white matter. Prefrontal, parieto-occipital and temporal cortices appeared to be particularly affected. A number of sub-cortical areas also showed decreased volumes including the hippocampus and putamen. In contrast, callosal areas were increased in VCFS.
In relation to controls, subjects with VCFS present with an overall reduction in brain volumes and specific abnormalities in multiple cortical and subcortical brain regions. These abnormalities may explain partly why VCFS is associated with a greatly increased risk of psychosis and other psychiatric disorders.
Morphological abnormalities of the anterior cingulate (AC) occur in patients with schizophrenia and in symptomatic high-risk individuals, and may be predictive of subsequent psychosis. We investigated AC sulcal morphology in the Edinburgh High Risk Study cohort to see if such abnormalities are evident and predict psychosis in patients’ relatives. We also investigated the association of the cingulate sulcus (CS) and paracingulate sulcus (PCS) variants with intelligence quotient (IQ).
Patients and methods
We compared cingulate and paracingulate sulcal anatomy, using reliable standardised measurements, blind to group membership, in those at high genetic risk (n = 146), first episode patients (n = 34) and healthy controls (n = 36); and compared high-risk subjects who did (n = 17) or did not develop schizophrenia.
Interruptions of the cingulate sulcus were more common in high-risk individuals and in those with schizophrenia, in both hemispheres, compared to controls. When separated by gender, these results were only present in males in the left hemisphere and only in females in the right hemisphere. A well-formed paracingulate sulcus was less common in high-risk participants and patients with schizophrenia, compared to controls; but this association was only present in males. These morphological variants of the paracingulate sulcus and the continuous cingulate sulcus were also associated with the higher IQ in male high-risk individuals.
An interrupted cingulate sulcus pattern in both males and females and paracingulate morphology in males are associated with increased genetic risk of schizophrenia. Associations between cingulate and paracingulate morphology and premorbid IQ scores provide evidence that intellectual ability could be related to particular cytoarchitectural brain regions. Given that these sulci develop in early fetal life, such findings presumably reflect early neurodevelopmental abnormalities of genetic origin, although environmental effects and interactions cannot be ruled out.
Schizophrenia, which is linked to a range of physical health conditions, might share intrinsic inflammatory disease pathways with type-two diabetes mellitus (T2DM). Psychotropic medication has presented a major confounder in examining this association. First-episode psychosis (FEP) patients present an interesting cohort to study this potential association, being generally younger with less comorbidity, and with limited exposure to antipsychotic medication.
To assess whether FEP, which could be described as ‘developing schizophrenia’, is associated with prediabetes, or ‘developing diabetes’, to determine whether intrinsic disease links could cause the conditions to develop in unison.
Using PRISMA criteria, we searched Embase, Medline, PsychInfo, Web of Science, and Google Scholar to 6th January 2016. We assessed case-control studies with biochemical assessment of prediabetic states in FEP patients alongside matched controls.
Twelve studies were included, involving 1137 participants. Several measurements examined prediabetes, including fasting plasma glucose, impaired glucose tolerance, and insulin resistance. Pooled analysis found FEP to be related to impaired glucose tolerance (mean difference 1.31 [0.37, 2.25]), insulin resistance (mean difference 0.30 [0.18, 0.42]), and the number of patients with impaired glucose tolerance (odds ratio 5.44 [2.63–11.27]).
Our findings suggest a potential link between prediabetic markers, in particular impaired glucose tolerance and insulin resistance, and FEP. However, we cannot establish causality, and the studies contributing to this review were at some risk of bias. Nevertheless, the findings might help to explain the increased prevalence of T2DM in patients with schizophrenia and could have implications for the management of schizophrenia patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Background: Cervical sponylotic myelopathy (CSM) may present with neck and arm pain. This study investiagtes the change in neck/arm pain post-operatively in CSM. Methods: This ambispective study llocated 402 patients through the Canadian Spine Outcomes and Research Network. Outcome measures were the visual analogue scales for neck and arm pain (VAS-NP and VAS-AP) and the neck disability index (NDI). The thresholds for minimum clinically important differences (MCIDs) for VAS-NP and VAS-AP were determined to be 2.6 and 4.1. Results: VAS-NP improved from mean of 5.6±2.9 to 3.8±2.7 at 12 months (P<0.001). VAS-AP improved from 5.8±2.9 to 3.5±3.0 at 12 months (P<0.001). The MCIDs for VAS-NP and VAS-AP were also reached at 12 months. Based on the NDI, patients were grouped into those with mild pain/no pain (33%) versus moderate/severe pain (67%). At 3 months, a significantly high proportion of patients with moderate/severe pain (45.8%) demonstrated an improvement into mild/no pain, whereas 27.2% with mild/no pain demonstrated worsening into moderate/severe pain (P <0.001). At 12 months, 17.4% with mild/no pain experienced worsening of their NDI (P<0.001). Conclusions: This study suggests that neck and arm pain responds to surgical decompression in patients with CSM and reaches the MCIDs for VAS-AP and VAS-NP at 12 months.
Schizophrenia is a highly heritable disorder, linked to several structural abnormalities of the brain. More specifically, previous findings have suggested that increased gyrification in frontal and temporal regions are implicated in the pathogenesis of schizophrenia.
The current study included participants at high familial risk of schizophrenia who remained well (n = 31), who developed sub-diagnostic symptoms (n = 28) and who developed schizophrenia (n = 9) as well as healthy controls (HC) (n = 16). We first tested whether individuals at high familial risk of schizophrenia carried an increased burden of trait-associated alleles using polygenic risk score analysis. We then assessed the extent to which polygenic risk was associated with gyral folding in the frontal and temporal lobes.
We found that individuals at high familial risk of schizophrenia who developed schizophrenia carried a significantly greater burden of risk-conferring variants for the disorder compared to those at high risk (HR) who developed sub-diagnostic symptoms or remained well and HC. Furthermore, within the HR cohort, there was a significant and positive association between schizophrenia polygenic risk score and bilateral frontal gyrification.
These results suggest that polygenic risk for schizophrenia impacts upon early neurodevelopment to confer greater gyral folding in adulthood and an increased risk of developing the disorder.
OBJECTIVES/SPECIFIC AIMS: Our objectives with this project are to engage communities through technology creating a communication channel with affected communities and stakeholders about mosquito-borne illness, vector control and environmental health risk. Furthermore, engaging communities to electronically map ecological risks that impact mosquito-borne illness with the goal of creating a mobile application that will work as an ecological surveillance against mosquito proliferation and potential mosquito population reduction, and finally pilot test and evaluate potential benefits in communities where the application was used. METHODS/STUDY POPULATION: We propose a methodology to perform formative community work that will underscore a distributed, democratized ecological surveillance through an integration of multidimensional health behavior theories that address the challenges of ZIKV in Culebra, a marginalized island community off the coast of the main island of Puerto Rico. Using participatory design, we will develop, test, and evaluate users’ experiences towards mobile applications using qualitative (interviews) and quantitative (survey) methodologies. A mobile application with the capacity of mapping, use of social-media, crowdsourcing, and photo-voice in a dynamic and simple way will allow community members to alert “hot-zone” locations to the stakeholders interested in creating ecological action in their community. This multidimensional concept integrates explanatory and prospective approaches and will generate systematic short-term solutions for mosquito control and long-term solutions providing the necessary tools for community empowerment. RESULTS/ANTICIPATED RESULTS: Our proposed design will facilitate better understanding of the interactions between community members and socio-environmental determinants of mosquito-borne diseases. Furthermore, our proposed project will not only facilitate communication among members of a community, but also it will provide a platform for engagement and empowerment, establishing a change in the preventive paradigm of how communities face the negative impacts of micro-ecologies that surround them. DISCUSSION/SIGNIFICANCE OF IMPACT: Our proposed community collaboratory mHealth tool mZAP! (Zonas, Accion y Proteccion) will address the lack of community participation efforts against mosquito-borne diseases contributed simultaneously by the disengagement and disempowerment of community members. mZAP! will serve as an innovative tool to engage marginalized and communities made vulnerable in Puerto Rico. This approach should be successful as Puerto Rico is one of the most digitally connected countries in Latin America, with high mobile phone usage rates and social media use. Using mZAP!, communities will report and map breeding sites, use social media and crowd sensing, targeting against powerful tools against mosquito ecologies in their own environments. This application could result in an effective way to change the paradigms for public health approaches to use Information Communications Technologies (ICTs) to empower communities.
There is a lack of evidence pointing to the efficacy of any specific psychotherapy for adults with anorexia nervosa (AN). The aim of this study was to compare three psychological treatments for AN: Specialist Supportive Clinical Management, Maudsley Model Anorexia Nervosa Treatment for Adults and Enhanced Cognitive Behavioural Therapy.
A multi-centre randomised controlled trial was conducted with outcomes assessed at pre-, mid- and post-treatment, and 6- and 12-month follow-up by researchers blind to treatment allocation. All analyses were intention-to-treat. One hundred and twenty individuals meeting diagnostic criteria for AN were recruited from outpatient treatment settings in three Australian cities and offered 25–40 sessions over a 10-month period. Primary outcomes were body mass index (BMI) and eating disorder psychopathology. Secondary outcomes included depression, anxiety, stress and psychosocial impairment.
Treatment was completed by 60% of participants and 52.5% of the total sample completed 12-month follow-up. Completion rates did not differ between treatments. There were no significant differences between treatments on continuous outcomes; all resulted in clinically significant improvements in BMI, eating disorder psychopathology, general psychopathology and psychosocial impairment that were maintained over follow-up. There were no significant differences between treatments with regard to the achievement of a healthy weight (mean = 50%) or remission (mean = 28.3%) at 12-month follow-up.
The findings add to the evidence base for these three psychological treatments for adults with AN, but the results underscore the need for continued efforts to improve outpatient treatments for this disorder.
There is now a well-established link between childhood adversity (CA) and schizophrenia. Similar structural abnormalities to those found in schizophrenia including alterations in grey-matter volume have also been shown in those who experience CA.
We examined whether global estimates of cortical thickness or surface area were altered in those familial high-risk subjects who had been referred to a social worker or the Children's Panel compared to those who had not.
We found that the cortical surface area of those who were referred to the Children's Panel was significantly smaller than those who had not been referred, but cortical thickness was not significantly altered. There was also an effect of social work referral on cortical surface area but not on thickness.
Cortical surface area increases post-natally more than cortical thickness. Our findings suggest that CA can influence structural changes in the brain and it is likely to have a greater impact on cortical surface area than on cortical thickness.
Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis.
Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n = 23) and not exposed to cannabis (n = 32) in the intervening period was compared using tensor-based morphometry (TBM).
Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected = 0.029, t = 3.88) and left superior frontal lobe GM (pcorrected = 0.026, t = 4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval.
Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.
A masked analysis of videotaped assessments of people at high genetic risk of schizophrenia revealed that those who subsequently went on to develop schizophrenia used significantly more second-person pronouns. This was evident before diagnosis, at two separate assessments approximately 18 months apart. This supports the view that people who go on to develop schizophrenia may have an abnormality in the deictic frame of interpersonal communication – that is, the distinction between concepts being self-generated or from elsewhere may be blurred prior to the onset of a diagnosis of schizophrenia.
No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia.
To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia.
Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance.
Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F=7.66, P=0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis.
These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.
The limitations of current diagnostic categories are well recognised but their rationale, advantages and utility are often ignored. The scientific support for a ‘continuum of psychosis' is limited, and the examination of whether categories, a continuum or more than one continua, and alternatives such as subtypes or hybrid models, best account for the distributions of symptoms in populations has simply not been done. There is a lack of discussion, let alone consensus, about the critical aspects of psychosis to measure, the best ways to quantify those and how these would be applied in clinical practice. Systematic studies are needed to evaluate which of a range of plausible approaches to the classification of psychosis is most useful before change could be justified.
Lead poisoning is a preventable condition caused by exposure to environmental sources such as lead-containing dust or lead-painted consumer products. The history of lead poisoning prevention has been defined to some extent by the quality of the analytical methods available for lead measurements whether in environmental samples or biological tissues and fluids. The quality of blood lead methods has improved so greatly over the last three decades that we now know far more about the adverse health effects from low-level exposures. Recent evidence suggests that effects such as deficit in IQ occur below the current (periodically revised) U.S. CDC threshold of 10 μg/dL, such that no safe threshold appears to exist for children. Improvements in analytical techniques have also had an impact on the environmental measurement quality, yet many environmental thresholds have remained unchanged for decades. In light of our current understanding of the adverse health effects at low levels of exposure, new thresholds for lead in children’s products have been introduced by the U.S. CPSC. The adequacy of current analytical techniques to detect lead accurately at the new, lower thresholds is questionable. XRF offers the advantage of being rapid and nondestructive compared to techniques such as AAS that require extensive sample preparation. However, the accuracy of handheld XRF determinations of lead in painted toys is generally limited. A brief comparative study on the performance of several analytical techniques for the determination of lead in toys is presented at the end of this paper.
Neuropsychological deficits in schizophrenia patients and their relatives have been thought to represent possible genetic vulnerability markers or endophenotypes of the disorder. The present study describes results from the Edinburgh High Risk Study of computerized testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) on a group at genetic high risk (HR) of schizophrenia and a control group.
A total of 97 HR and 25 control participants were assessed on three tests from the CANTAB – spatial span, spatial working memory, and Stockings of Cambridge. Analyses of covariance were used to compare the HR and control groups on the main outcome measures whilst controlling for intelligence quotient (IQ). Subsequent analysis examined the effects of the presence of symptoms on group differences.
HR participants had significantly reduced spatial memory capacity [F(1, 118)=4.06, p=0.046] and significantly reduced planning processing speed [F(1, 116)=4.16, p=0.044] compared with controls even after controlling for general intelligence (IQ). Although HR individuals made more errors and showed poorer problem-solving and strategy performance compared with controls, these differences were not significant after controlling for IQ. Subsequent analysis indicated that the presence or absence of psychotic symptoms in the HR group did not influence these specific cognitive deficits.
Spatial memory capacity and planning processing speed may represent cognitive endophenotypes characterising the genetic predisposition to schizophrenia in this HR group.
Functional brain abnormalities have been repeatedly demonstrated in schizophrenia but there is little data concerning their progression. For such studies to have credibility it is first important to establish the reproducibility of functional imaging techniques. The current study aimed to examine these factors in healthy controls and in unmedicated subjects at high genetic risk of the disorder: (i) to examine the reproducibility of task-related activation patterns, (ii) to determine if there were any progressive functional changes in high-risk subjects versus controls reflecting inheritance of the schizophrenic trait, and (iii) to examine changes over time in relation to fluctuating positive psychotic symptoms (i.e. state effects).
Subjects were scanned performing the Hayling sentence completion test on two occasions 18 months apart. Changes in activation were examined in controls and high-risk subjects (n=16, n=63). Reproducibility was assessed for controls and high-risk subjects who remained asymptomatic at both time points (n=16, n=32).
Intra-class correlation values indicated good agreement between scanning sessions. No significant differences over time were seen between the high-risk and control group; however, comparison of high-risk subjects who developed symptoms versus those who remained asymptomatic revealed activation increases in the left middle temporal gyrus (p=0.026).
The current results suggest that functional changes over time occur in the lateral temporal cortex as high genetic risk subjects become symptomatic, further, they indicate the usefulness of functional imaging tools for investigating progressive changes associated with state and trait effects in schizophrenia.
Epidemiological studies have demonstrated high hospitalization rates attributable to influenza and RSV in children aged <24 months. We prospectively recruited 977 children, aged <6 years, presenting with influenza-like illnesses at a hospital during two winter seasons between 2002 and 2004. Nasopharyngeal aspirates were performed and sent for viral immunofluorescence and PCR. Influenza and respiratory syncytial virus (RSV) rates were stratified by age, in-patient/outpatient status and clinical diagnosis. The influenza A and RSV hospitalization incidence rates were 4 and 11/10 000 person-months respectively, whereas the accident and emergency (A&E) outpatient rates were both 32/10 000 person-months in those aged <6 years. The influenza A and RSV hospitalization rates were highest in children aged <24 months and <12 months (9·1 and 35·7/10 000 person-months) respectively. Infection rates were particularly high in those aged <6 months for both viruses. The age-specific influenza A and RSV A&E admission rates were highest in those aged >6 months and those aged <12 months, respectively (43 and 92·5/10 000 person-months, respectively). In conclusion, these high paediatric RSV and influenza incidence rates can be used to inform UK policy on childhood influenza immunization and subsequent RSV immunization in the future.