Pituitary volume reduction in schizophrenia following cognitive behavioural therapy

Cognitive behavioural therapy (CBT) for psychosis (CBTp) aims to lower the stress of psychotic symptoms. Given that the pituitary is involved in stress regulation, CBT-led stress reduction may be accompanied by a change in pituitary volume. This study aimed to determine whether CBTp reduces pituitary volume in schizophrenia. The relation between pre-therapy memory and CBTp-led pituitary volume change was also examined given that poor memory relates to a blunted cortisol awakening response, denoting impaired stress response, in schizophrenia. Pituitary volume was measured at baseline in 40 schizophrenia or schizoaffective disorder patients and 30 healthy participants before therapy. Pituitary volume was measured again 6–9 months after patients had either received CBTp in addition to standard care (CBTp + SC, n = 24), or continued with standard care alone (SC, n = 16). CBTp + SC and SC groups were compared on pituitary volume change from baseline to follow-up. Pre-therapy memory performance (Hopkins Verbal Learning and Wechsler Memory Scale – Logical memory) was correlated with baseline-to-follow-up pituitary volume change. Pituitary volume reduced over time in CBTp + SC patients. Additionally, pre-therapy verbal learning correlated more strongly with longitudinal pituitary volume reduction in the CBTp + SC group than the SC group. To conclude, CBTp reduces pituitary volume in schizophrenia most likely by enhancing stress regulation and lowering the distress due to psychotic symptoms

Baseline Shifts do not Predict Attentional Modulation of Target Processing During Feature-Based Visual Attention

Cues that direct selective attention to a spatial location have been observed to increase baseline neural activity in visual areas that represent a to-be-attended stimulus location. Analogous attention-related baseline shifts have also been observed in response to attention-directing cues for non-spatial stimulus features. It has been proposed that baseline shifts with preparatory attention may serve as the mechanism by which attention modulates the responses to subsequent visual targets that match the attended location or feature. Using functional MRI, we localized color- and motion-sensitive visual areas in individual subjects and investigated the relationship between cue-induced baseline shifts and the subsequent attentional modulation of task-relevant target stimuli. Although attention-directing cues often led to increased background neural activity in feature specific visual areas, these increases were not correlated with either behavior in the task or subsequent attentional modulation of the visual targets. These findings cast doubt on the hypothesis that attention-related shifts in baseline neural activity result in selective sensory processing of visual targets during feature-based selective attention

Neural changes following cognitive behaviour therapy for psychosis: A longitudinal study

A growing body of evidence demonstrates that persistent positive symptoms, particularly delusions, can be improved by cognitive behaviour therapy for psychosis. Heightened perception and processing of threat are believed to constitute the genesis of delusions. The present study aimed to examine functional brain changes following cognitive behaviour therapy for psychosis. The study involved 56 outpatients with one or more persistent positive distressing symptoms of schizophrenia. Twenty-eight patients receiving cognitive behaviour therapy for psychosis for 6–8 months in addition to their usual treatment were matched with 28 patients receiving treatment as usual. Patients’ symptoms were assessed by a rater blind to treatment group, and they underwent functional magnetic resonance imaging during an affect processing task at baseline and end of treatment follow-up. The two groups were comparable at baseline in terms of clinical and demographic parameters and neural and behavioural responses to facial and control stimuli. The cognitive behaviour therapy for psychosis with treatment-as-usual group (22 subjects) showed significant clinical improvement compared with the treatment-as-usual group (16 subjects), which showed no change at follow-up. The cognitive behaviour therapy for psychosis with treatment-as-usual group, but not the treatment-as-usual group, showed decreased activation of the inferior frontal, insula, thalamus, putamen and occipital areas to fearful and angry expressions at treatment follow-up compared with baseline. Reduction of functional magnetic resonance imaging response during angry expressions correlated directly with symptom improvement. This study provides the first evidence that cognitive behaviour therapy for psychosis attenuates brain responses to threatening stimuli and suggests that cognitive behaviour therapy for psychosis may mediate symptom reduction by promoting processing of threats in a less distressing way

The role of work-integrated learning in the development of entrepreneurs

This study explored the ways that work-integrated learning (WIL) influences the development of entrepreneurs. Seven alumni from Canada and the United Kingdom, who experienced differing forms of WIL during their degree, participated in qualitative in-depth interviews and provided rich pictures. A rich picture is a pictorial representation of a situation, including what happened, who was involved, how the participant perceived the situation. During the interviews, participants reflected on how WIL impacted their career and they created rich pictures to depict their perception of an entrepreneur and what influenced them to become an entrepreneur. Several important themes emerged and included seizing opportunities, thinking “outside the box,” being resilient during difficult times, and the importance of networks. The influence of WIL was important for all participants and provided the framework of support that enabled the participants to manage difficult times and turn disruption into opportunity

Endothelial Cell Capture of Heparin-Binding Growth Factors under Flow

Circulation is an important delivery method for both natural and synthetic molecules, but microenvironment interactions, regulated by endothelial cells and critical to the molecule's fate, are difficult to interpret using traditional approaches. In this work, we analyzed and predicted growth factor capture under flow using computer modeling and a three-dimensional experimental approach that includes pertinent circulation characteristics such as pulsatile flow, competing binding interactions, and limited bioavailability. An understanding of the controlling features of this process was desired. The experimental module consisted of a bioreactor with synthetic endothelial-lined hollow fibers under flow. The physical design of the system was incorporated into the model parameters. The heparin-binding growth factor fibroblast growth factor-2 (FGF-2) was used for both the experiments and simulations. Our computational model was composed of three parts: (1) media flow equations, (2) mass transport equations and (3) cell surface reaction equations. The model is based on the flow and reactions within a single hollow fiber and was scaled linearly by the total number of fibers for comparison with experimental results. Our model predicted, and experiments confirmed, that removal of heparan sulfate (HS) from the system would result in a dramatic loss of binding by heparin-binding proteins, but not by proteins that do not bind heparin. The model further predicted a significant loss of bound protein at flow rates only slightly higher than average capillary flow rates, corroborated experimentally, suggesting that the probability of capture in a single pass at high flow rates is extremely low. Several other key parameters were investigated with the coupling between receptors and proteoglycans shown to have a critical impact on successful capture. The combined system offers opportunities to examine circulation capture in a straightforward quantitative manner that should prove advantageous for biologicals or drug delivery investigations

Mapping depression in schizophrenia: A functional magnetic resonance imaging study

Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. Depressive symptoms are common in schizophrenia, often left untreated, and associated with a high relapse rate, suicidal ideation, increased mortality, reduced social adjustment and poor quality of life. The neural mechanisms underlying depression in psychosis are poorly understood. Given reports of altered brain response to negative facial affect in depressive disorders, we examined brain response to emotive facial expressions in relation to levels of depression in people with psychosis. Seventy outpatients (final N = 63) and 20 healthy participants underwent functional magnetic resonance imaging during an implicit affect processing task involving presentation of facial expressions of fear, anger, happiness as well as neutral expressions and a (no face) control condition. All patients completed Beck Depression Inventory (BDI-II) and had their symptoms assessed on the Positive and Negative Syndrome Scale (PANSS). In patients, depression (BDI-II) scores associated positively with activation of the left thalamus, extending to the putamen-globus pallidus, insula, inferior-middle frontal and para-post-pre-central gyri during fearful expressions. Furthermore, patients with moderate-to-severe depression had significantly higher activity in these brain regions during fearful expressions relative to patients with no, minimal, or mild depression and healthy participants. The study provides first evidence of enhanced brain response to fearful facial expressions, which signal an uncertain source of threat in the environment, in patients with psychosis and a high level of self-reported depression

PAH–DNA Adducts, Cigarette Smoking, GST Polymorphisms, and Breast Cancer Risk

BackgroundPolycyclic aromatic hydrocarbons (PAHs) may increase breast cancer risk, and the association may be modified by inherited differences in deactivation of PAH intermediates by glutathione S-transferases (GSTs). Few breast cancer studies have investigated the joint effects of multiple GSTs and a PAH biomarker.ObjectiveWe estimated the breast cancer risk associated with multiple polymorphisms in the GST gene (GSTA1, GSTM1, GSTP1, and GSTT1) and the interaction with PAH–DNA adducts and cigarette smoking.MethodsWe conducted unconditional logistic regression using data from a population-based sample of women (cases/controls, respectively): GST polymorphisms were genotyped using polymerase chain reaction and matrix-assisted laser desorption/ionization time-of-flight assays (n = 926 of 916), PAH–DNA adduct blood levels were measured by competitive enzyme-linked immunosorbent assay (n = 873 of 941), and smoking status was assessed by in-person questionnaires (n = 943 of 973).ResultsOdds ratios for joint effects on breast cancer risk among women with at least three variant alleles were 1.56 [95% confidence interval (CI), 1.13–2.16] for detectable PAH–DNA adducts and 0.93 (95% CI, 0.56–1.56) for no detectable adducts; corresponding odds ratios for three or more variants were 1.18 (95% CI, 0.82–1.69) for ever smokers and 1.44 (95% CI, 0.97–2.14) for never smokers. Neither interaction was statistically significant (p = 0.43 and 0.62, respectively).ConclusionWe found little statistical evidence that PAHs interacted with GSTT1, GSTM1, GSTP1, and GSTA1 polymorphisms to further increase breast cancer risk