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Adolescent subthreshold emotional symptoms arise from impaired self-referential information-processing and approach–avoidance behaviour network integration, which compromises goal evaluation and pursuit strategies.
We investigated whether impairment of negative emotion (goal) reappraisal strategies (self-focussing and self-distancing) generates emotional symptoms (emotional disorders precursors).
Using functional magnetic resonance imaging and a triple-network model (default mode, executive control and salience), functional connectivity differences within and between networks, and their modulation by task and relationships with emotional symptoms were determined in healthy adolescent girls (N = 202) grouped by presence or absence of emotional symptoms.
The groups differed in spectral power distribution and in dorsal default mode network and right executive control network modulation when self-focussing and self-distancing, respectively. Girls without emotional symptoms had greater spectral power and less network modulation. Greater spectral power was associated with reduced emotional symptoms and less dorsal default mode network modulation when self-focussing.
The early phases of anxiety and depressive disorders in adolescence are marked by emotional symptoms that usually emerge in the context of negative life events. To contend with the negative effect of such events, a typical reappraisal strategy is to distance oneself and switch the focus of one's thinking. This brain-imaging study in adolescent girls prone to the development of emotional disorders has found functional changes in key neural networks that are involved in reappraisal and shown that this process is impaired. This is important because it provides an early indication of these common disorders and a potential target for psychological interventions.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.
Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.
This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.
This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.
Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention.
Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity.
Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA.
DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.
Subsyndromal emotional symptoms in adolescence may represent precursors for full-blown emotional disorders in early adulthood. Understanding the neurobiological mechanisms that drive this development is essential for prevention.
Self-referential processing and emotion regulation are remodelled substantively during adolescence, therefore this study examined integration of key neural networks involved in these processes.
At baseline, clinical and resting-state functional magnetic resonance imaging data were collected for 88 adolescent girls (mean age 15 years), and 71 of these girls underwent repeat clinical assessment after 2 years. These 71 girls were then partitioned into two groups depending on the presence (ES+) or absence (ES−) of emotional symptoms, and differences in dynamic functional network connectivity were determined and correlated with clinical variables.
The two groups displayed a differential pattern of functional connectivity involving the left lateral prefrontal network (LPFN). Specifically, in the ES+ group this network displayed positive coupling with the right LPFN but negative coupling with the default mode network, and the inverse of this pattern was found in the ES− group. Furthermore, the coupling strengths between left and right LPFN at the irst time point predicted follow-up depression and state anxiety scores.
Our findings suggest that in adolescent girls, emotional symptoms may emerge as a result of impaired integration between networks involved in self-referential information processing and approach-avoidance behaviours. These impairments can compromise the pursuit of important goals and have an impact on emotion processing and finally may lead to the development of emotional disorders, such as anxiety and depression in adulthood.
Objectives: Apathy is a debilitating symptom of Huntington’s disease (HD) and manifests before motor diagnosis, making it an excellent therapeutic target in the preclinical phase of Huntington’s disease (prHD). HD is a neurological genetic disorder characterized by cognitive and motor impairment, and psychiatric abnormalities. Apathy is not well characterized within the prHD. In previous literature, damage to the caudate and putamen has been correlated with increased apathy in other neurodegenerative and movement disorders. The objective of this study was to determine whether apathy severity in individuals with prHD is related to striatum volumes and cognitive control. We hypothesized that, within prHD individuals, striatum volumes and cognitive control scores would be related to apathy. Methods: We constructed linear mixed models to analyze striatum volumes and cognitive control, a composite measure that includes tasks assessing with apathy scores from 797 prHD participants. The outcome variable for each model was apathy, and the independent variables for the four separate models were caudate volume, putamen volume, cognitive control score, and motor symptom score. We also included depression as a covariate to ensure that our results were not solely related to mood. Results: Caudate and putamen volumes, as well as measures of cognitive control, were significantly related to apathy scores even after controlling for depression. Conclusions: The behavioral apathy expressed by these individuals was related to regions of the brain commonly associated with isolated apathy, and not a direct result of mood symptoms. (JINS, 2019, 25, 462–469)
Studies conducted in sub-Saharan Africa suggest a high prevalence of depression and suicidality among adolescents living with HIV (ALWH). This is an important public health issue because depression is known to compromise HIV treatment adherence. However, the drivers of depression and suicidality in this population are unclear. We conducted a cross-sectional study to estimate the associations between internalized stigma, bullying, major depressive disorder, and suicidality.
We conducted a cross-sectional survey between November 2016 and March 2017, enrolling a consecutive sample of 224 ALWH aged 13–17 years. We collected information on demographic characteristics, internalized HIV-related stigma (using the six-item Internalized AIDS-Related Stigma Scale), bullying victimization (using the nine-item Social and Health Assessment Peer Victimization Scale), major depressive disorder [using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)], and suicidality (also using the MINI-KID). We fitted multivariable logistic regression models to estimate the associations between stigma, bullying, major depressive disorder, and suicidality.
Thirty-seven participants (16%) had major depressive disorder, 30 (13%) had suicidality, and nine (4%) had high-risk suicidality. Ninety-one participants (41%) had high levels of internalized stigma, while 97 (43%) reported two or more bullying events in the past year. In multivariable logistic regression models, major depressive disorder had a statistically significant association with bullying (AOR = 1.09; 95% CI 1.00–1.20; p = 0.04); while suicidality (low, moderate, high risk) had statistically significant associations with both bullying (AOR = 1.09; 95% CI 1.01–1.17; p = 0.02) and stigma (AOR = 1.30; 95% CI 1.03–1.30; p = 0.02).
Among ALWH in rural Uganda, stigma and bullying are strongly associated with major depressive disorder and suicidality. There is a need to incorporate psychological interventions in the mainstream HIV care to address these challenges for optimal management of HIV among ALWH.
The aims of this study were to determine the presence and quantities of antioxidative status and oxidative stress (OS) variables in the seminal plasma and spermatozoa of bulls of varying age during cold and warm periods of the year, and to establish the correlation of these variables with semen quality parameters. The study was conducted on two groups each comprising nine Simmental bulls: one group contained younger animals (aged 2 to 4 years) and the second older animals (aged 5 to 10 years). Semen samples were collected using an artificial vagina for biochemical analysis. Seminal plasma and spermatozoa activities of total superoxide dismutase (TSOD), manganese superoxide dismutase (MnSOD), copper–zinc superoxide dismutase (CuZnSOD), catalase (CAT), selenium-dependent glutathione peroxidase, reduced glutathione and concentrations of total protein (TP), thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) were determined. Several antioxidants in seminal plasma were also determined: total glutathione peroxidase (TGSH-Px), selenium-independent glutathione peroxidase (Non-SeGSH-Px), uric acid, albumins (ALB) and alkaline phosphatase (ALP). Significantly higher spermatozoa motility was observed during the cold v. warm period, and a significantly higher volume and total number of spermatozoa per ejaculate was observed in older than in younger bulls. Significantly higher values of ALP, TP and ALB were found in seminal plasma of older bulls than in younger bulls during the warm period. The seminal plasma of younger bulls showed significantly higher activities of TSOD, MnSOD, CuZnSOD, TGSH-Px and Non-SeGSH-Px. Younger bulls had significantly higher PCC concentration and activity of CAT in seminal plasma than older bulls during the cold period. Significantly higher concentrations of PCC and TBARS, and activities of TSOD, MnSOD and CuZnSOD were established in spermatozoa of the younger than in older bulls during the warm period. It could be concluded that antioxidative and OS variables differ significantly depending on bull age and time of year. Younger bulls were more sensitive to elevated ambient temperatures during the warm period, when the higher enzymatic antioxidative protection in seminal plasma and spermatozoa were insufficient to counteract the intensive oxidative processes in spermatozoa, which eventually resulted in decreased spermatozoa motility. The estimation of antioxidative and OS variables in seminal plasma and spermatozoa may have practical value for the assessment of bull semen quality.
Objectives: Huntington’s disease (HD) is a debilitating genetic disorder characterized by motor, cognitive and psychiatric abnormalities associated with neuropathological decline. HD pathology is the result of an extended chain of CAG (cytosine, adenine, guanine) trinucleotide repetitions in the HTT gene. Clinical diagnosis of HD requires the presence of an otherwise unexplained extrapyramidal movement disorder in a participant at risk for HD. Over the past 15 years, evidence has shown that cognitive, psychiatric, and subtle motor dysfunction is evident decades before traditional motor diagnosis. This study examines the relationships among subcortical brain volumes and measures of emerging disease phenotype in prodromal HD, before clinical diagnosis. Methods: The dataset includes 34 cognitive, motor, psychiatric, and functional variables and five subcortical brain volumes from 984 prodromal HD individuals enrolled in the PREDICT HD study. Using cluster analyses, seven distinct clusters encompassing cognitive, motor, psychiatric, and functional domains were identified. Individual cluster scores were then regressed against the subcortical brain volumetric measurements. Results: Accounting for site and genetic burden (the interaction of age and CAG repeat length) smaller caudate and putamen volumes were related to clusters reflecting motor symptom severity, cognitive control, and verbal learning. Conclusions: Variable reduction of the HD phenotype using cluster analysis revealed biologically related domains of HD and are suitable for future research with this population. Our cognitive control cluster scores show sensitivity to changes in basal ganglia both within and outside the striatum that may not be captured by examining only motor scores. (JINS, 2017, 23, 159–170)
School attendance rates in sub-Saharan Africa are among the lowest worldwide, placing children at heightened risk for poor educational and economic outcomes. One understudied risk factor for missed schooling is household water insecurity, which is linked to depression among women and may increase children's water-fetching burden at the expense of educational activities, particularly among children of depressed caregivers. In this study conducted in rural Uganda, we assessed the association between household water insecurity and child school participation and the mediating pathways behind these associations.
We conducted a population-based, cross-sectional study of female household heads (N = 257) and their children ages 5–17 (N = 551) in the rural regions surrounding the town of Mbarara, in southwestern Uganda. We used multivariable linear regressions to estimate the association between water insecurity and missed schooling. We then assessed the extent to which the association was mediated by caregiver depression.
Among children, water insecurity had a statistically significant association with the number of missed school days (a standard deviation increase in water insecurity resulted in 0.30 more missed school days in the last week). The estimated association was partially mediated by caregiver depression. When stratified by sex, this mediating pathway remained significant for boys, but not among girls.
Water insecurity is a risk factor for missed schooling among children in rural Uganda. Caregiver depression partially mediated this relationship. Also addressing caregiver mental health in water insecure families may more fully address the needs of sub-Saharan African families and promote educational participation among youth.
Objectives: One of the most prominent features of schizophrenia is relatively lower general cognitive ability (GCA). An emerging approach to understanding the roots of variation in GCA relies on network properties of the brain. In this multi-center study, we determined global characteristics of brain networks using graph theory and related these to GCA in healthy controls and individuals with schizophrenia. Methods: Participants (N=116 controls, 80 patients with schizophrenia) were recruited from four sites. GCA was represented by the first principal component of a large battery of neurocognitive tests. Graph metrics were derived from diffusion-weighted imaging. Results: The global metrics of longer characteristic path length and reduced overall connectivity predicted lower GCA across groups, and group differences were noted for both variables. Measures of clustering, efficiency, and modularity did not differ across groups or predict GCA. Follow-up analyses investigated three topological types of connectivity—connections among high degree “rich club” nodes, “feeder” connections to these rich club nodes, and “local” connections not involving the rich club. Rich club and local connectivity predicted performance across groups. In a subsample (N=101 controls, 56 patients), a genetic measure reflecting mutation load, based on rare copy number deletions, was associated with longer characteristic path length. Conclusions: Results highlight the importance of characteristic path lengths and rich club connectivity for GCA and provide no evidence for group differences in the relationships between graph metrics and GCA. (JINS, 2016, 22, 240–249)
On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2–73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.
In this paper, we demonstrate deposition methods and conditions that allow the control of the electrical properties of doped ZnTe grown by RF magnetron sputtering using both nitrogen and copper as dopants. The carrier density of the films was characterized using a van der Pauw Hall effect measurement method. We demonstrate how the concentration of nitrogen in the plasma during the growth of the film impacts the conductivity of the ZnTe films. Films with hole concentrations in excess of 1018 cm-3 and a high degree of crystallinity were successfully grown. Similarly, we demonstrate that the hole concentration in the Cu-doped ZnTe can be varied by varying the amount of copper introduced in the films. We also observe that annealing the copper doped ZnTe films increases the carrier density, whereas annealing the nitrogen doped ZnTe films causes a decrease in carrier concentration and conductivity.
Structural brain measures are employed as endophenotypes in the search for schizophrenia susceptibility genes. We analyzed two independent structural imaging datasets with voxel-based morphometry and with source-based morphometry, a multivariate, independent components analysis, to determine the stability and heritability of regional gray matter concentration abnormalities in schizophrenia. The samples comprised 209 and 102 patients with schizophrenia and 208 and 96 healthy volunteers, respectively. The second sample additionally included non-ill siblings of participants with and without schizophrenia. A standard voxel-based analysis showed reproducible regional gray matter deficits in the affected participants compared with unrelated, unaffected controls in both datasets: patients showed significant gray matter concentration deficits in cortical frontal, temporal, and insular lobes. Source-based morphometry (SBM) was applied to the gray matter images of the entire sample to determine the effects of diagnosis on networks of covarying structures. The SBM analysis extracted 24 significant sets of covarying regions (components). Four of these components showed significantly lower gray matter concentrations in patients (p < .05). We determined the familiality of the observed SBM components based on 66 sibling pairs (25 discordant for schizophrenia). Two components, one including the medial frontal, insular, inferior frontal, and temporal lobes, and the other including the posterior occipital lobe, showed significant familiality (p < .05). We conclude that structural brain deficits in schizophrenia are replicable, and that SBM can extract unique familial and likely heritable components. SBM provides a useful data reduction technique that can provide measures that may serve as endophenotypes for schizophrenia.
In the summer of 2009, an outbreak of verocytotoxigenic Escherichia coli O157 (VTEC O157) was identified in visitors to a large petting farm in South East England. The peak attack rate was 6/1000 visitors, and highest in those aged <2 years (16/1000). We conducted a case-control study with associated microbiological investigations, on human, animal and environmental samples. We identified 93 cases; 65 primary, 13 secondary and 15 asymptomatic. Cases were more likely to have visited a specific barn, stayed for prolonged periods and be infrequent farm visitors. The causative organism was identified as VTEC O157 PT21/28 with the same VNTR profile as that isolated in faecal specimens from farm animals and the physical environment, mostly in the same barn. Contact with farm livestock, especially ruminants, should be urgently reviewed at the earliest suspicion of a farm-related VTEC O157 outbreak and appropriate risk management procedures implemented without delay.
Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving.
We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center.
Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA.
Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined.
In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.
The Roman town of Forum Novum lies in the Sabine hills to the northeast of Rome. Its study forms part of the British School at Rome's Tiber Valley Project, a collaborative research initiative which studies the Tiber valley as the hinterland of Rome, tracing the impact of Rome's development on the history of its settlement, economy, and cultural identity from 1000 B.C. to A.D. 1300 (Patterson and Millett 1999; Patterson et al. 2000) (fig. 1). The project draws on the extensive work carried out in this area to produce a new, material-based history of the valley. While the project seeks to re-evaluate past survey material, a vital contrast is provided by the development of new field projects to fill the gaps in settlement knowledge. Three main lacunae have been identified: the study of urban centres; the dearth of data from the E bank of the Tiber; and the poor understanding of the late-antique and early Mediaeval landscape. Forum Novum offers an opportunity to address all these lacunae.
Urbanism forms a key research theme for the Tiber Valley Project. In marked contrast to the intensity of archaeological work on rural settlement in this area, there has been little systematic research on towns. Study has tended to concentrate on the excavation of monumental structures or, more rarely, the investigation of single and exceptional towns such as Ostia and Rome itself. Surprisingly little is known of the organization of the smaller towns and knowledge of their history is based largely on the epigraphic and documentary evidence.
Two alternatives to standard tensile testing of arteries are discussed. The first involves inflation of arteries and simultaneous measurement of radial displacement with intra-vascular ultrasound (IVUS). The second involves the measurement of load versus displacement during micro-indentation of the intimal surface. The IVUS technique is used to study the nonlinear stiffening of porcine coronaries during inflation and, ultimately, it may provide a method to determine mechanical properties in vivo. Processing of the IVUS data relies on accurate determination of the luminal/intimal and medial/advential boundaries during inflation. The microindentation technique is used to study the effect of loading rate on tissue stiffness, recovery, and internal dissipation. Ultimately, this technique may provide a method to measure local mechanical properties in the vicinity of an atherosclerotic plaque, for example. Accurate determination of the initial contact point between the indenter and intima is required, however. The techniques appear to successfully capture significant, nonlinear, time-dependent properties of arterial tissue.
Spectra of Active Galactic Nuclei (AGN) indicate that in their central parts a composite motion of emission gas exists. An analysis of broad as well as narrow lines of active galaxies can give information about gas dynamics in central part of these objects (see e.g. Netzer 1990, Osterbrock 1990). Here we present the investigation of the Hβ and O III[4959,5007] line shapes of the two Sy 1 galaxis: Mrk 817 and III Zw2.