Evaluating Acquisition Time of rfMRI in the Human Connectome Project for Early Psychosis. How Much Is Enough?

Resting-state functional MRI (rfMRI) correlates activity across brain regions to identify functional connectivity networks. The Human Connectome Project (HCP) for Early Psychosis has adopted the protocol of the HCP Lifespan Project, which collects 20 min of rfMRI data. However, because it is difficult for psychotic patients to remain in the scanner for long durations, we investigate here the reliability of collecting less than 20 min of rfMRI data. Varying durations of data were taken from the full datasets of 11 subjects. Correlation matrices derived from varying amounts of data were compared using the Bhattacharyya distance, and the reliability of functional network ranks was assessed using the Friedman test. We found that correlation matrix reliability improves steeply with longer windows of data up to 11–12 min, and ≥14 min of data produces correlation matrices within the variability of those produced by 18 min of data. The reliability of network connectivity rank increases with increasing durations of data, and qualitatively similar connectivity ranks for ≥10 min of data indicates that 10 min of data can still capture robust information about network connectivities

Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology

Reduced Exercise Tolerance and Pulmonary Capillary Recruitment with Remote Secondhand Smoke Exposure

RATIONALE: Flight attendants who worked on commercial aircraft before the smoking ban in flights (pre-ban FAs) were exposed to high levels of secondhand smoke (SHS). We previously showed never-smoking pre-ban FAs to have reduced diffusing capacity (Dco) at rest. METHODS: To determine whether pre-ban FAs increase their Dco and pulmonary blood flow (Qc) during exercise, we administered a symptom-limited supine-posture progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake (VO2) achieved by FAs. After 30 min rest, we then measured Dco and Qc at 20, 40, 60, and 80 percent of maximum observed work. RESULTS: The FAs with abnormal resting Dco achieved a lower level of maximum predicted work and VO2 compared to those with normal resting Dco (mean±SEM; 88.7±2.9 vs. 102.5±3.1%predicted VO2; p = 0.001). Exercise limitation was associated with the FAs' FEV(1) (r = 0.33; p = 0.003). The Dco increased less with exercise in those with abnormal resting Dco (mean±SEM: 1.36±0.16 vs. 1.90±0.16 ml/min/mmHg per 20% increase in predicted watts; p = 0.020), and amongst all FAs, the increase with exercise seemed to be incrementally lower in those with lower resting Dco. Exercise-induced increase in Qc was not different in the two groups. However, the FAs with abnormal resting Dco had less augmentation of their Dco with increase in Qc during exercise (mean±SEM: 0.93±0.06 vs. 1.47±0.09 ml/min/mmHg per L/min; p<0.0001). The Dco during exercise was inversely associated with years of exposure to SHS in those FAs with ≥10 years of pre-ban experience (r = -0.32; p = 0.032). CONCLUSIONS: This cohort of never-smoking FAs with SHS exposure showed exercise limitation based on their resting Dco. Those with lower resting Dco had reduced pulmonary capillary recruitment. Exposure to SHS in the aircraft cabin seemed to be a predictor for lower Dco during exercise

Cognitive reactivity: cultural adaptation and psychometric testing of the Persian version of the Leiden Index of Depression Sensitivity Revised (LEIDS-R) in an Iranian sample

Cognitive reactivity (CR) to the experimental induction of sad mood has been found to predict relapse in recovered depressed patients. The Leiden Index of Depression Sensitivity Revised (LEIDS-R) is a self-report measure of CR. The aim of the present study was to establish the validity and reliability of the Persian version of the LEIDS-R. The participants were recovered depressed and non-depressed Iranian individuals (n = 833). The analyses included content validation, factor analysis, construct validity, and reliability testing. Preliminary construct validation analysis confirmed that factor analysis was appropriate for the Persian version of the LEIDS-R. Factor analysis displayed similar factor loadings to the original English version. The total internal consistency of the translated version, which was assessed using Cronbach’s alpha coefficient, was equal to 0.90. The test-retest reliability of the total score was equal to that of the test-retest conducted after a two-week interval at 0.94. Content validity, face validity, and construct validity, as well as reliability analysis were all found to be satisfactory for the Persian version of the LEIDS-R. The Persian version of the LEIDS-R appears to be valid and reliable for use in future studies, and has properties comparable to the original version and to that obtained in previous studies

Helping someone with problem drug use: a delphi consensus study of consumers, carers, and clinicians

<p>Abstract</p> <p>Background</p> <p>Problem use of illicit drugs (i.e. drug abuse or dependence) is associated with considerable health and social harms, highlighting the need for early intervention and engagement with health services. Family members, friends and colleagues play an important role in supporting and assisting individuals with problem drug use to seek professional help, however there are conflicting views about how and when such support should be offered. This paper reports on the development of mental health first aid guidelines for problem drug use in adults, to help inform community members on how to assist someone developing problem drug use or experiencing a drug-related crisis.</p> <p>Methods</p> <p>A systematic review of the scientific and lay literature was conducted to develop a 228-item survey containing potential first-aid strategies to help someone developing a drug problem or experiencing a drug-related crisis. Three panels of experts (29 consumers, 31 carers and 27 clinicians) were recruited from Australia, Canada, New Zealand, the United Kingdom, and the United States. Panel members independently rated the items over three rounds, with strategies reaching consensus on importance written into the guidelines.</p> <p>Results</p> <p>The overall response rate across three rounds was 80% (86% consumers, 81% carers, 74% clinicians). 140 first aid strategies were endorsed as essential or important by 80% or more of panel members. The endorsed strategies provide information and advice on what is problem drug use and its consequences, how to approach a person about their problem drug use, tips for effective communication, what to do if the person is unwilling to change their drug use, what to do if the person does (or does not) want professional help, what are drug-affected states and how to deal with them, how to deal with adverse reactions leading to a medical emergency, and what to do if the person is aggressive.</p> <p>Conclusions</p> <p>The guidelines provide a consensus-based resource for community members who want to help someone with a drug problem. It is hoped that the guidelines will lead to better support and understanding for those with problem drug use and facilitate engagement with professional help.</p

Connectomic markers of disease expression, genetic risk and resilience in bipolar disorder.

Bipolar disorder (BD) is characterized by emotional dysregulation and cognitive deficits associated with abnormal connectivity between subcortical-primarily emotional processing regions-and prefrontal regulatory areas. Given the significant contribution of genetic factors to BD, studies in unaffected first-degree relatives can identify neural mechanisms of genetic risk but also resilience, thus paving the way for preventive interventions. Dynamic causal modeling (DCM) and random-effects Bayesian model selection were used to define and assess connectomic phenotypes linked to facial affect processing and working memory in a demographically matched sample of first-degree relatives carefully selected for resilience (n=25), euthymic patients with BD (n=41) and unrelated healthy controls (n=46). During facial affect processing, patients and relatives showed similarly increased frontolimbic connectivity; resilient relatives, however, evidenced additional adaptive hyperconnectivity within the ventral visual stream. During working memory processing, patients displayed widespread hypoconnectivity within the corresponding network. In contrast, working memory network connectivity in resilient relatives was comparable to that of controls. Our results indicate that frontolimbic dysfunction during affect processing could represent a marker of genetic risk to BD, and diffuse hypoconnectivity within the working memory network a marker of disease expression. The association of hyperconnectivity within the affect-processing network with resilience to BD suggests adaptive plasticity that allows for compensatory changes and encourages further investigation of this phenotype in genetic and early intervention studies

Comparison of techniques used to count single-celled viable phytoplankton

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Applied Phycology 24 (2012): 751-758, doi:10.1007/s10811-011-9694-z.Four methods commonly used to count phytoplankton were evaluated based upon the precision of concentration estimates: Sedgewick Rafter and membrane filter direct counts, flow cytometry, and flow-based imaging cytometry (FlowCAM). Counting methods were all able to estimate the cell concentrations, categorize cells into size classes, and determine cell viability using fluorescent probes. These criteria are essential to determine whether discharged ballast water complies with international standards that limit the concentration of viable planktonic organisms based on size class. Samples containing unknown concentrations of live and UV-inactivated phytoflagellates (Tetraselmis impellucida) were formulated to have low concentrations (<100 ml-1) of viable phytoplankton. All count methods used chlorophyll a fluorescence to detect cells and SYTOX fluorescence to detect non-viable cells. With the exception of one sample, the methods generated live and non-viable cell counts that were significantly different from each other, although estimates were generally within 100% of the ensemble mean of all subsamples from all methods. Overall, percent coefficient of variation (CV) among sample replicates was lowest in membrane filtration sample replicates, and CVs for all four counting methods were usually lower than 30% (although instances of ~60% were observed). Since all four methods were generally appropriate for monitoring discharged ballast water, ancillary considerations (e.g., ease of analysis, sample processing rate, sample size, etc.) become critical factors for choosing the optimal phytoplankton counting method.This study was supported by the U.S. Coast Guard Research and Development Center under contract HSCG32-07- X-R00018. Partial research support to DMA and DMK was provided through NSF International Contract 03/06/394, and Environmental Protection Agency Grant RD-83382801-0

Family-based clusters of cognitive test performance in familial schizophrenia

BACKGROUND: Cognitive traits derived from neuropsychological test data are considered to be potential endophenotypes of schizophrenia. Previously, these traits have been found to form a valid basis for clustering samples of schizophrenia patients into homogeneous subgroups. We set out to identify such clusters, but apart from previous studies, we included both schizophrenia patients and family members into the cluster analysis. The aim of the study was to detect family clusters with similar cognitive test performance. METHODS: Test scores from 54 randomly selected families comprising at least two siblings with schizophrenia spectrum disorders, and at least two unaffected family members were included in a complete-linkage cluster analysis with interactive data visualization. RESULTS: A well-performing, an impaired, and an intermediate family cluster emerged from the analysis. While the neuropsychological test scores differed significantly between the clusters, only minor differences were observed in the clinical variables. CONCLUSIONS: The visually aided clustering algorithm was successful in identifying family clusters comprising both schizophrenia patients and their relatives. The present classification method may serve as a basis for selecting phenotypically more homogeneous groups of families in subsequent genetic analyses

Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia