An MRI study of pituitary volume and parasuicidal behavior in teenagers with first-presentation borderline personality disorder

This structural magnetic resonance imaging study examined the relationship between pituitary gland volume (PGV) and lifetime number of parasuicidal behaviors in a first-presentation, teenage borderline personality disorder (BPD) sample with minimal exposure to treatment. Hierarchical regression analysis revealed that age and number of parasuicidal behaviors were significant predictors of PGV. These findings indicate that parasuicidal behavior in BPD might be associated with greater activation of the hypothalamic-pituitary-adrenal (HPA) axis. Further studies are required using direct neuroendocrine measures and exploring other parameters of self-injurious behavior, such as recency of self-injurious behavior, intent to die and medical threat.

Pituitary volume in teenagers with first-presentation borderline personality disorder

This study used magnetic resonance imaging to examine pituitary gland volume (PGV) in teenage patients with a first presentation of borderline personality disorder (BPD). No difference in PGV was observed between healthy controls (n=20) and the total BPD cohort (n=20). However, within the BPD cohort, those exposed to childhood trauma (n=9) tended to have smaller pituitaries (-18%) than those with no history of childhood trauma (n=10). These preliminary findings suggest that exposure to childhood trauma, rather than BPD, per se, might be associated with reduced PGV, possibly reflecting hypothalamic-pituitary-adrenal axis dysfunction.

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis

Background We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. Methods Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. Results Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (−6%; p = .032). Conclusions The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

Stress, the hippocampus and the HPA axis: Implications for the development of psychotic disorders

The experience of stress is commonly implicated in models of the onset of psychotic disorders. However, prospective studies investigating associations between biological markers of stress and the emergence of psychotic disorders are limited and inconclusive. One biological system proposed as the link between the psychological experience of stress and the development of psychosis is the Hypothalamic-Pituitary-Adrenal (HPA) axis. This paper summarizes and discusses evidence supporting a role for HPA-axis dysfunction in the early phase of schizophrenia and related disorders. METHOD A selective review of psychiatric and psychological research on stress, coping, HPA-axis, the hippocampus and psychotic disorders was performed, with a particular focus on the relationship between HPA-axis dysfunction and the onset of psychotic disorders. RESULTS Individual strands of past research have suggested that the HPA-axis is dysfunctional in at least some individuals with established psychotic disorders; that the hippocampus is an area of the brain that appears to be implicated in the onset and maintenance of psychotic disorders; and that an increase in the experience of stress precedes the onset of a psychotic episode in some individuals. Models of the onset and maintenance of psychotic disorders that link these individual strands of research and strategies for examining these models are proposed in this paper. CONCLUSIONS The current literature provides some evidence that the onset of psychotic disorders may be associated with a higher rate of stress and changes to the hippocampus. It is suggested that future research should investigate whether a relationship exists between psychological stress, HPA-axis functioning and the hippocampus in the onset of these disorders. Longitudinal assessment of these factors in young people at 'ultra' high risk of psychosis and first-episode psychosis cohorts may enhance understanding of the possible interaction between them in the early phases of illness.

Importance of animal models in schizophrenia research

Objective This review aims to summarize the importance of animal models for research on psychiatric illnesses, particularly schizophrenia. Method and Results Several aspects of animal models are addressed, including animal experimentation ethics and theoretical considerations of different aspects of validity of animal models. A more specific discussion is included on two of the most widely used behavioural models, psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, followed by comments on the difficulty of modelling negative symptoms of schizophrenia. Furthermore, we emphasize the impact of new developments in molecular biology and the generation of genetically modified mice, which have generated the concept of behavioural phenotyping. Conclusions Complex psychiatric illnesses, such as schizophrenia, cannot be exactly reproduced in species such as rats and mice. Nevertheless, by providing new information on the role of neurotransmitter systems and genes in behavioural function, animal 'models' can be an important tool in unravelling mechanisms involved in the symptoms and development of such illnesses, alongside approaches such as post-mortem studies, cognitive and psychophysiological studies, imaging and epidemiology.

Stochastic analysis of a radial-inflow turbine in the presence of parametric uncertainties

This paper presents an uncertainty quantification study of the performance analysis of the high pressure ratio single stage radial-inflow turbine used in the Sundstrand Power Systems T-100 Multi-purpose Small Power Unit. A deterministic 3D volume-averaged Computational Fluid Dynamics (CFD) solver is coupled with a non-statistical generalized Polynomial Chaos (gPC) representation based on a pseudo-spectral projection method. One of the advantages of this approach is that it does not require any modification of the CFD code for the propagation of random disturbances in the aerodynamic and geometric fields. The stochastic results highlight the importance of the blade thickness and trailing edge tip radius on the total-to-static efficiency of the turbine compared to the angular velocity and trailing edge tip length. From a theoretical point of view, the use of the gPC representation on an arbitrary grid also allows the investigation of the sensitivity of the blade thickness profiles on the turbine efficiency. The gPC approach is also applied to coupled random parameters. The results show that the most influential coupled random variables are trailing edge tip radius coupled with the angular velocity.

Deficits on self ordered tasks associated with hyperostosis frontalis interna

A 74 year old patient, EW, with dorsolateral frontal cortical compression due to hyperostosis frontalis interna, in the absence of the Morgagni or Stewart-Morel syndromes, is described. In addition to conventional neuropsychological measures EW was administered one nonspatial and two spatial self ordered working memory tasks, as well as a standard measure of fluid intelligence or g. She showed impaired performance on all three self ordered working memory tasks compared with a normal control group of 10 subjects matched for age, education, sex, and IQ. By contrast, her performance on the fluid intelligence test was comparable with that of the controls. It is concluded that the compression of dorsolateral frontal cortex accompanying hyperostosis frontalis interna may produce selective cognitive impairment.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production.

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. Objectives: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. Methods: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. Results: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. Conclusions: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen’s d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen’s d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen’s d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen’s d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen’s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) using genome-wide search

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10 -6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

The first mitochondrial genome of the sepsid fly Nemopoda mamaevi Ozerov, 1997 (Diptera: Sciomyzoidea: Sepsidae), with mitochondrial genome phylogeny of cyclorrhapha

Sepsid flies (Diptera: Sepsidae) are important model insects for sexual selection research. In order to develop mitochondrial (mt) genome data for this significant group, we sequenced the first complete mt genome of the sepsid fly Nemopoda mamaevi Ozerov, 1997. The circular 15,878 bp mt genome is typical of Diptera, containing all 37 genes usually present in bilaterian animals. We discovered inaccurate annotations of fly mt genomes previously deposited on GenBank and thus re-annotated all published mt genomes of Cyclorrhapha. These re-annotations were based on comparative analysis of homologous genes, and provide a statistical analysis of start and stop codon positions. We further detected two 18 bp of conserved intergenic sequences from tRNAGlu-tRNAPhe and ND1-tRNASer(UCN) across Cyclorrhapha, which are the mtTERM binding site motifs. Additionally, we compared automated annotation software MITOS with hand annotation method. Phylogenetic trees based on the mt genome data from Cyclorrhapha were inferred by Maximum-likelihood and Bayesian methods, strongly supported a close relationship between Sepsidae and the Tephritoidea.

Numerical investigation of aerosol particle transport and deposition in realistic lung airway

Different human activities like combustion of fossil fuels, biomass burning, industrial and agricultural activities, emit a large amount of particulates into the atmosphere. As a consequence, the air we inhale contains significant amount of suspended particles, including organic and inorganic solids and liquids, as well as various microorganism, which are solely responsible for a number of pulmonary diseases. Developing a numerical model for transport and deposition of foreign particles in realistic lung geometry is very challenging due to the complex geometrical structure of the human lung. In this study, we have numerically investigated the airborne particle transport and its deposition in human lung surface. In order to obtain the appropriate results of particle transport and deposition in human lung, we have generated realistic lung geometry from the CT scan obtained from a local hospital. For a more accurate approach, we have also created a mucus layer inside the geometry, adjacent to the lung surface and added all apposite mucus layer properties to the wall surface. The Lagrangian particle tracking technique is employed by using ANSYS FLUENT solver to simulate the steady-state inspiratory flow. Various injection techniques have been introduced to release the foreign particles through the inlet of the geometry. In order to investigate the effects of particle size on deposition, numerical calculations are carried out for different sizes of particles ranging from 1 micron to 10 micron. The numerical results show that particle deposition pattern is completely dependent on its initial position and in case of realistic geometry; most of the particles are deposited on the rough wall surface of the lung geometry instead of carinal region.

Managing mental health co-morbidities in hepatitis C: A systematic review of clinical guidelines

BACKGROUND Mental health co-morbidities are prevalent in hepatitis C (HCV), and in practice often considered a contraindication for initiation of treatment. A systematic review was conducted to explore whether and how current HCV clinical practice guidelines address pre-existing mental health co-morbidities. METHODS A review of the literature was undertaken to identify guidelines for the management of HCV, published in English, between 2002 and January 2015. Characteristics of the guidelines were recorded and key themes on mental health were summarized across predefined stages in the patient journey (diagnosis, pre-HCV drug therapy, on HCV drug therapy, post-HCV drug therapy, advanced disease or palliative care). RESULTS Twenty-five HCV clinical guidelines were included. Referral to psychiatrist is generally recommended as pre- and in-treatment assessment of mental health co-morbidities but HCV guidelines do not offer explicit instructions on how to manage mental health co-morbidities. Post-treatment assessment of mental health co-morbidities were lacking. Conclusions Current chronic HCV clinical guidelines are limited in their advice to clinicians regarding the management of mental health co-morbidities.

Meta-analysis of structural imaging findings in Attention-Deficit/Hyperactivity Disorder

Background Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. Methods We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Results Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference equal to .408, p less than .001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. Conclusions This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.