Data Gathering Bias: Trait Vulnerability to Psychotic Symptoms?

Background Jumping to conclusions (JTC) is associated with psychotic disorder and psychotic symptoms. If JTC represents a trait, the rate should be (i) increased in people with elevated levels of psychosis proneness such as individuals diagnosed with borderline personality disorder (BPD), and (ii) show a degree of stability over time. Methods The JTC rate was examined in 3 groups: patients with first episode psychosis (FEP), BPD patients and controls, using the Beads Task. PANSS, SIS-R and CAPE scales were used to assess positive psychotic symptoms. Four WAIS III subtests were used to assess IQ. Results A total of 61 FEP, 26 BPD and 150 controls were evaluated. 29 FEP were revaluated after one year. 44% of FEP (OR = 8.4, 95% CI: 3.9-17.9) displayed a JTC reasoning bias versus 19% of BPD (OR = 2.5, 95% CI: 0.8-7.8) and 9% of controls. JTC was not associated with level of psychotic symptoms or specifically delusionality across the different groups. Differences between FEP and controls were independent of sex, educational level, cannabis use and IQ. After one year, 47.8% of FEP with JTC at baseline again displayed JTC. Conclusions JTC in part reflects trait vulnerability to develop disorders with expression of psychotic symptoms.

Differential regulation of Adiponectin receptor gene expression by Adiponectin and Leptin in Myotubes derived from obese and diabetic individuals

Objective: This study aimed to investigate the regulation of adiponectin receptors 1 (AdipoR1) and 2 (AdipoR2) gene expression in primary skeletal muscle myotubes, derived from human donors, after exposure to globular adiponectin (gAd) and leptin. Research Methods and Procedures: Four distinct primary cell culture groups were established [ Lean, Obese, Diabetic, Weight Loss (Wt Loss); n = 7 in each] from rectus abdominus muscle biopsies obtained from surgical patients. Differentiated myotube cultures were exposed to gAd (0.1 mug/mL) or leptin (2.5 mug/mL) for 6 hours. AdipoR1 and AdipoR2 gene expression was measured by real-time polymerase chain reaction analysis. Results: AdipoR1 mRNA expression in skeletal muscle myotubes derived from Lean subjects (p < 0.05) was stimulated 1.8-fold and 2.5-fold with gAd and leptin, respectively. No increase in AdipoR1 gene expression was measured in myotubes derived from Obese, Diabetic, or Wt Loss subjects. AdipoR2 mRNA expression was unaltered after gAd and leptin exposure in all myotube groups. Discussion: Adiponectin and leptin are rapid and potent stimulators of AdipoR1 in myotubes derived from lean healthy individuals. This effect was abolished in myotubes derived from obese, obese diabetic subjects, and obese-prone individuals who had lost significant weight after bariatric surgery. The incapacity of skeletal muscle of obese and diabetic individuals to respond to exogenous adiponectin and leptin may be further suppressed as a result of impaired regulation of the AdipoR1 gene.

Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice

Objective Spondyloarthritides (SpA) occur in 1% of the population and include ankylosing spondylitis (AS) and arthropathy of inflammatory bowel disease (IBD), with characteristic spondylitis, arthritis, enthesitis, and IBD. Genetic studies implicate interleukin-23 (IL-23) receptor signaling in the development of SpA and IBD, and IL-23 overexpression in mice is sufficient for enthesitis, driven by entheseal-resident T cells. However, in genetically prone individuals, it is not clear where IL-23 is produced and how it drives the SpA syndrome, including IBD or subclinical gut inflammation of AS. Moreover, it is unclear why specific tissue involvement varies between patients with SpA. We undertook this study to determine the location of IL-23 production and its role in SpA pathogenesis in BALB/c ZAP-70W163C-mutant (SKG) mice injected intraperitoneally with β-1,3-glucan (curdlan). Methods Eight weeks after curdlan injection in wild-type or IL-17A-/- SKG or BALB/c mice, pathology was scored in tissue sections. Mice were treated with anti-IL-23 or anti-IL-22. Cytokine production and endoplasmic reticulum (ER) stress were determined in affected organs. Results In curdlan-treated SKG mice, arthritis, enthesitis, and ileitis were IL-23 dependent. Enthesitis was specifically dependent on IL-17A and IL-22. IL-23 was induced in the ileum, where it amplified ER stress, goblet cell dysfunction, and proinflammatory cytokine production. IL-17A was pathogenic, while IL-22 was protective against ileitis. IL-22+CD3- innate-like cells were increased in lamina propria mononuclear cells of ileitis-resistant BALB/c mice, which developed ileitis after curdlan injection and anti-IL-22. Conclusion In response to systemic β-1,3-glucan, intestinal IL-23 provokes local mucosal dysregulation and cytokines driving the SpA syndrome, including IL-17/IL-22-dependent enthesitis. Innate IL-22 production promotes ileal tolerance.

Facial affect recognition and schizotypal personality characteristics

Aim: Deficits in facial affect recognition are well established in schizophrenia, yet relatively little research has examined facial affect recognition in hypothetically psychosis-prone or ‘schizotypal’ individuals. Those studies that have examined social cognition in psychosis-prone individuals have paid little attention to the association between facial emotion recognition and particular schizotypal personality features. The present study therefore sought to investigate relationships between facial emotion recognition and the different aspects of schizotypy.

Methods: Facial affect recognition accuracy was examined in 50 psychiatrically healthy individuals assessed for level of schizotypy using the Schizotypal Personality Questionnaire. This instrument provides a multidimensional measure of schizophrenia proneness, encompassing ‘cognitive-perceptual’, ‘interpersonal’ and ‘disorganized’ features of schizotypy. It was hypothesized that the cognitive-perceptual and interpersonal aspects of schizotypy would be associated with difficulties identifying facial expressions of emotion during a forced-choice recognition task using a standardized series of colour photographs.

Results: As predicted, interpersonal aspects of schizotypy (particularly social anxiety) were associated with reduced accuracy on the facial affect recognition task, but there was no association between affect recognition accuracy and cognitive-perceptual features of schizotypy.

Conclusions: These results suggest that subtle deficits in facial affect recognition in otherwise psychiatrically healthy individuals may be related to the vulnerability for interpersonal communication difficulties, as seen in schizophrenia.

Infantile epileptic encephalopathy with hypsarrhythmia (infantile spasms/west syndrome) and immunity

West syndrome is a severe epilepsy, occurring in infancy, that comprises epileptic seizures known as spasms, in clusters, and a unique EEG pattern, hypsarrhythmia, with psychomotor regression. Maturation of the brain is a crucial component. The onset is within the first year of life, before 12 months of age. Patients are classified as cryptogenic (10 to 20%), when there are no known or diagnosed previous cerebral insults, and symptomatic (80 to 90%), when associated with pre-existing cerebral damages. The time interval from a brain insult to infantile spasms onset ranged from 6 weeks to 11 months. West syndrome has a time-limited natural evolutive course, usually disappearing by 3 or 4 years of age. In 62% of patients, there are transitions to another age-related epileptic encephalopathies, the Lennox-Gastaut Syndrome and severe epilepsy with multiple independent foci. Spontaneous remission and remission after viral infections may occur. Therapy with ACTH and corticosteroids are the most effective. Reports about intravenous immunoglobulins action deserve attention. There is also immune dysfunction, characterized mainly by anergy, impaired cell-mediated immunity, presence of immature thymocytes in peripheral blood, functional impairment of T lymphocytes induced by plasma inhibitory factors, and altered levels of immunoglobulins. Changes in B lymphocytes frequencies and increased levels of activated B cells have been reported. Sensitized lymphocytes to brain extract were also described. Infectious diseases are frequent and may, sometimes, cause fatal outcomes. Increase of pro-inflamatory cytokines in serum and cerebrospinal fluid of epileptic patients were reported. Association with specific HLA antigens was described by several authors (HLA-DR7, HLA-A7, HLA-DRw52, and HLA-DR5). Auto-antibodies to brain antigens, of several natures (N-methyl-d-aspartate glutamate receptor, gangliosides, brain tissue extract, synaptic membrane, and others), were described in epileptic patients and in epileptic syndromes. Experimental epilepsy studies with anti-brain antibodies demonstrated that epileptiform discharges can be obtained, producing hyperexcitability leading to epilepsy. We speculate that in genetically prone individuals, previous cerebral lesions may sensitize immune system and trigger an autoimmune disease. Antibody to brain antigens may be responsible for impairment of T cell function, due to plasma inhibitory effect and also cause epilepsy in immature brains. © 2008 Bentham Science Publishers Ltd.

Development of an Electrochemical Insulin Sensor Based on a High Affinity DNA Sequence Found in the Insulin-linked Polymorphic Region

The detection of pertinent biomarkers has the potential provide an early indication of disease progression before considerable damage has been incurred. A decrease in an individual’s sensitivity to insulin, which may be quantified as the ratio of insulin to glucose in the blood after a glucose pulse, has recently been reported as an early predictor of insulin-dependent diabetes mellitus. Routine measurement of insulin levels is therefore desirable in the care of diabetes-prone individuals. A rapid, simple, and reagentless method for insulin detection would allow for wide-spread screenings that provide earlier signs of diabetes onset. The aim of this thesis is to develop a folding-base electrochemical sensor for the detection of insulin. The sensor described herein consists of a DNA probe immobilized on a gold disc electrode via an alkanethiol linker and embedded in an alkanethiol self-assembled monolayer. The probe is labeled with a redox reporter, which readily transfers electrons to the gold electrode in the absence of insulin. In the presence of insulin, electron transfer is inhibited, presumably due to a binding-induced conformational or dynamic change in the DNA probe that significantly alters the electron-tunneling pathway. A 28-base segment of the insulin-linked polymorphic region that has been reported to bind insulin with high affinity serves as the capture element of the DNA probe. Three probe constructs that vary in their secondary structure and position of the redox label are evaluated for their utility as insulin-sensing elements on the electrochemical platform. The effects of probe modification on secondary structure are also evaluated using circular dichroism spectroscopy.

Walking when intoxicated : an investigation of the factors which influence individuals' drink walking intentions

Annually, in Australia, 10-15% of all road-related fatalities involve pedestrians. Of those pedestrians fatally injured, approximately 45% were walking while intoxicated or 'drink walking'. Drink walking is increasing in prevalence and younger persons may be especially prone to engage in this behaviour and, thus, are at heightened risk of being injured or killed. Presently, limited research is available regarding the factors which influence individuals to drink walk. This study explored young people's (17-25 years) intentions to drink walk, using an extended Theory of Planned Behaviour (TPB). Participants (N = 215), completed a self-report questionnaire which assessed the standard TPB constructs (attitude, subjective norm, perceived behavioural control) as well as the extended constructs of risk perception, anticipated regret, and past behaviour. It was hypothesised that the standard TPB constructs would significantly predict individuals' reported intentions to drink walk and that the additional constructs would predict intentions over and above the TPB constructs. The TPB variables significantly predicted 63.2% of the variance in individuals' reported intentions to drink walk, and the additional variables, combined, explained a further 6.1% of the variance. Of the additional constructs, anticipated regret and past behaviour, but not risk perception, were significant predictors of drink walking intentions. As one of the first studies to provide a theoretically-based investigation of factors influencing individuals' drink walking intentions, the current study's findings have potentially significant implications for understanding young people's decisions to drink walk and the design of future countermeasures to ultimately reduce this behaviour.

Citrus host utilisation by the Queensland fruit fly, Bactrocera tryoni (Frogatt) (Diptera:Tephritidae) : from individuals to populations

Fruit flies are the insects which cause maggots in your backyard fruit and vegetables. They are not just a nuisance to gardeners, but the single greatest insect threat to commercial and subsistence fruit growers throughout Asia, Australia and the Pacific. Queensland fruit fly, the focus of this PhD, costs Australia an estimated $100million per year. I focused specifically on how Queensland fruit fly uses different commercial citrus varieties. I identified specific plant related mechanisms which increase a fruit’s resistance to fruit fly attack. This information can be used by plant breeders to make fruit less prone to fruit fly damage.

MRI-based fatigue analysis predicts plaque vulnerability: A study comparing symptomatic and asymptomatic individuals

BACKGROUND: Rupture of atheromatous plaque in the carotid artery often leads to thrombosis and subsequent stroke. The mechanism of plaque rupture is not entirely clear but is thought to be a multi-factorial process involving thinning and weakening of the fibrous cap and biomechanical stress as the trigger leading to plaque rupture. As the cardiovascular system is a classic fatigue environment, the weakening of plaque leading to rupture may be a fatigue process, which is a symptomatically quiescent but potentially progressive failure process. In this study, we used a fatigue analysis based on in vivo magnetic resonance imaging (MRI) to investigate the rupture initiation location, crack propagation path and fatigue life within plaques of asymptomatic and symptomatic individuals. METHODS: Forty non-consecutive subjects (20 symptomatic and 20 asymptomatic) underwent high-resolution multi-sequence in vivo MRI of the carotid bifurcation. Fatigue analysis was performed based on the plaque geometry derived from in vivo MRI of the carotid artery at the point of maximum stenosis. Paris’ Law in fracture mechanics is adopted to determine the fatigue crack growth rate. Incremental crack propagation was dynamically simulated based on stress distributions. Plaque initiation location, crack propagation path and fatigue cycle of symptomatic and asymptomatic individuals were compared. RESULTS: Cracks were often found to begin at the lumen wall at areas of stress concentration. The preferred rupture direction was radial from the lumen center. The crack initially advanced slowly but accelerated as it developed, depending on plaque morphology. The fatigue cycles of symptomatic plaques were significantly less than those in the asymptomatic group (2.3 ± 0.9 vs 3.1 ± 0.7 (x106); p = 0.003). CONCLUSIONS: The number of cycles to rupture in symptomatic patients was higher than those predicted in asymptomatic patients by fatigue analysis, suggesting the possibility that plaques with a less fatigue life may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, fatigue analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma.

Structural analysis and magnetic resonance imaging predict plaque vulnerability: A study comparing symptomatic and asymptomatic individuals

Background: More than half of all cerebral ischemic events are the result of rupture of extracranial plaques. The clinical determination of carotid plaque vulnerability is currently based solely on luminal stenosis; however, it has been increasingly suggested that plaque morphology and biomechanical stress should also be considered. We used finite element analysis based on in vivo magnetic resonance imaging (MRI) to simulate the stress distributions within plaques of asymptomatic and symptomatic individuals. Methods: Thirty nonconsecutive subjects (15 symptomatic and 15 asymptomatic) underwent high-resolution multisequence in vivo MRI of the carotid bifurcation. Stress analysis was performed based on the geometry derived from in vivo MRI of the carotid artery at the point of maximal stenosis. The finite element analysis model considered plaque components to be hyperelastic. The peak stresses within the plaques of symptomatic and asymptomatic individuals were compared. Results: High stress concentrations were found at the shoulder regions of symptomatic plaques, and the maximal stresses predicted in this group were significantly higher than those in the asymptomatic group (508.2 ± 193.1 vs 269.6 ± 107.9 kPa; P = .004). Conclusions: Maximal predicted plaque stresses in symptomatic patients were higher than those predicted in asymptomatic patients by finite element analysis, suggesting the possibility that plaques with higher stresses may be more prone to be symptomatic and rupture. If further validated by large-scale longitudinal studies, biomechanical stress analysis based on high resolution in vivo MRI could potentially act as a useful tool for risk assessment of carotid atheroma. It may help in the identification of patients with asymptomatic carotid atheroma at greatest risk of developing symptoms or mild-to-moderate symptomatic stenoses, which currently fall outside current clinical guidelines for intervention.

Deficits in sensory prediction are related to delusional ideation in healthy individuals.

Motor control strongly relies on neural processes that predict the sensory consequences of self-generated actions. Previous research has demonstrated deficits in such sensory-predictive processes in schizophrenic patients and these low-level deficits are thought to contribute to the emergence of delusions of control. Here, we examined the extent to which individual differences in sensory prediction are associated with a tendency towards delusional ideation in healthy participants. We used a force-matching task to quantify sensory-predictive processes, and administered questionnaires to assess schizotypy and delusion-like thinking. Individuals with higher levels of delusional ideation showed more accurate force matching suggesting that such thinking is associated with a reduced tendency to predict and attenuate the sensory consequences of self-generated actions. These results suggest that deficits in sensory prediction in schizophrenia are not simply consequences of the deluded state and are not related to neuroleptic medication. Rather they appear to be stable, trait-like characteristics of an individual, a finding that has important implications for our understanding of the neurocognitive basis of delusions.

People who expect to enter psychotherapy are prone to believing that they have forgotten memories of childhood trauma and abuse.

We asked 1004 undergraduates to estimate both the probability that they would enter therapy and the probability that they experienced but could not remember incidents of potentially life-threatening childhood traumas or physical and sexual abuse. We found a linear relation between the expectation of entering therapy and the belief that one had, but cannot now remember, childhood trauma and abuse. Thus individuals who are prone to seek psychotherapy are also prone to accept a suggested memory of childhood trauma or abuse as fitting their expectations. In multiple regressions predicting the probability of forgotten memories of childhood traumas and abuse, the expectation of entering therapy remained as a substantial predictor when self-report measures of mood, anxiety, post-traumatic stress disorder symptom severity, and trauma exposure were included.

Group Dynamics in Sex Offender Treatment Involving Individuals with Personality Disorders

This qualitative investigation primarily employing a phenomenological perspective and psychoanalytic interview approach intends to provide contextual understanding of group dynamics in sex offender treatment involving individuals with strong features of personality disorders or Axis II psychopathology according to the Diagnostic and Statistical Manual of Mental Disorder (4 ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000). Of note, this study particularly focuses on the cluster B type (Narcissistic, Borderline, Histrionic, and Antisocial Personality Disorders), based on the assumption that this type is more interpersonally operational in its nature. The present study is based on semi-structured interviews of three clinicians who arecurrently providing group treatment for sex offenders. The interview was designed to elicit the participants' clinical observations of group dynamics involving group members with features of the Axis II, Cluster B type. In this study, 11 therapeutic factors postulated by Yalom (2005) were utilized to qualitatively investigate group dynamics. Analyses of qualitative data highlighted how group members with features of the Axis II, Cluster B type may distinctively affect group dynamics. Based on the results, group members with Axis II diagnoses, as reported bythe therapists who responded to this study, were observed to present with altruistic behaviors in group. In addition, motivation appeared to be one of the most influential factors in promoting and maintaining therapeutic group behaviors. Group members with antisocial features appeared to present with low motivation for treatment, and individualswith a pervasive history of criminal institutionalization seemed more prone to disengagement in group. Individuals with borderline and histrionic traits seemed to be interpersonally oriented and affectively engaged in group process. Persons with a narcissistic tendency also appeared to be interpersonally invested and showed altruistic behaviors, yet the importance of confirming their superiority seemed to outweigh the need for acceptance or approval from other group members. As briefly discussed above, the qualitative analyses of the current data showed that individuals with Axis II disorders, Cluster B type uniquely affect group dynamics, which suggest clinical considerations foreffective treatment planning, maintenance, and outcomes.

Understanding the risk of hypoglycaemia in older individuals with diabetes

Introduction: Although older individuals are more prone to hypoglycaemia, it is not known if they have sufficient understanding of the risks of hypoglycaemia or the factors that predispose to it. We evaluated the effectiveness of hypoglycaemia education and examined the factors that increased susceptibility to hypoglycaemia among older people with diabetes. Methods: Forty-five patients (male/female) aged >65 years and known to have diabetes were identified through outpatient clinics at a secondary care hospital. Information relating to education received, awareness of hypoglycaemia and associated risk factors was collected using a standard questionnaire. Additionally, data regarding demographics, treatment regimes, patient attitudes, hypoglycaemic awareness and risks and barriers to self-management of diabetes was collected. Patients were categorised as low, moderate and high risk based on their responses. Independent sample t-tests and Analysis of Variance were carried out to identify factors contributing to high hypoglycaemic risk. Results: Overall, 70% of the patients reported receiving education about hypoglycaemia from health professionals and 95% of them reported good understanding of hypoglycaemia and were able to self-test. Proportion of women receiving education was, however, lower than men (52% women versus 88% men). Compared with men, women were less likely to recognise (59 versus 73%), or act appropriately to a hypoglycaemic episode (59 versus 78%). The mean number of hypoglycaemic episodes per year (41 versus 12) and the duration of hypoglycaemia (9.9 versus 6.3 min) was also greater among women compared with men. The duration of diabetes (P = 0.018), female gender, type 1 diabetes (0.002) and lack awareness of medications causing hypos (P = 0.006) were strong predictors of hypoglycaemia risk. Conclusions: There are significant gaps in education around hypoglycaemia in older people with diabetes. Women, people with longer duration and type 1 diabetes in particular, need additional attention and future educational initiatives need to address these issues.