The continuum of quasi-psychotic beliefs and experiences in the Australian general public

When surveyed, many individuals without psychosis report a range of beliefs and experiences that are shared by patients with psychosis. This study aimed to examine quasi-psychotic beliefs and experiences in a sample of well Australians. 303 individuals were recruited from a defined catchment area as part of the Brisbane Psychosis Study. All subjects were screened with a modified SCAN in order to exclude psychoses. The Peters Delusional Inventory (PDI 40 items), items from the Chapmans' Psychosis Proneness Scale (PPS), the Communication Awareness Scale (CAS: a measure of awareness of thought disorder), items related to perceptions and beliefs from various schizotypy questionnaires and the Social Desirability (SD) items from the EPQ were administered. There was a significant negative correlation between age and total score on the PDI. There were significant positive correlations between the PDI, the PPS, the CAS and the items related to perception. There were no significant gender differences on any of the scores apart from SD (females had higher scores). Those with a positive family history of mental illness other than schizophrenia (n = 118) scored significantly higher on the PDI and scores related to perception, however they were no different on SD or the Psychosis Proneness items. There were no group differences on any of these items when those with a positive family history of schizophrenia (n = 27) were compared to the rest of the group. Well individuals who endorse delusional beliefs also tend to endorse items related to abnormal perceptions and awareness of thought disorder. The results of the study support the concept of a 'continuum of beliefs and experiences' in the general community that should inform our neurocognitive models of the symptoms of psychosis. The Stanley Foundation supported this project.

Working memory in schizophrenia and mania: Correlation with symptoms during the acute and subacute phases

Objective: The aims of this study were to examine working memory in the acute-subacute phase of schizophrenia and mania and to examine correlations between working memory and specific symptom domains. Method: Visuospatial working memory and symptom profiles were assessed in three groups (schizophrenia group, n=19; mania, n=12; controls, n=19) on two occasions separated by 4 weeks. Results: Both patient groups had significant deficits on working memory compared to the well controls and the schizophrenia and mania groups were equally impaired. All groups showed equivalent improvement over time. In the patient groups, impaired working memory was significantly correlated with the presence of both negative symptoms and positive thought disorder. Conclusion: Impaired wet-king memory is found in both schizophrenia and mania during the acute-subacute phases. Further research is required in order to clarify the neurocognitive mechanisms linking impaired working memory with both negative symptoms and positive thought disorder.

Molecular genetics of schizophrenia

1. Schizophrenia is a chronic, disabling brain disease that affects approxmately 1% of the world's population. It is characterized by delusions, hallucinations and formal thought disorder, together with a decline in socio-occupational functioning. While the causes for schizophrenia remain unknown, evidence from family, twin and adoption studies clearly demonstrates that it aggregates in families, with this clustering largely attributable to genetic rather than cultural or environmental factors. Identifying the genes involved, however, has proven to be a difficult task because schizophrenia is a complex trait characterized by an imprecise phenotype, the existence of phenocopies and the presence of low disease penetrance, 2. The current working hypothesis for schizophrenia causation is that multiple genes of small to moderate effect confer compounding risk through interactions with each other and with non-genetic risk factors, The same genes may be commonly involved in conferring risk across populations or they may vary in number and strength between different populations. To search for evidence of such genetic loci, both candidate gene and genome-wide linkage studies have been used in clinical cohorts collected from a variety of populations. Collectively, these works provide some evidence for the involvement of a number of specific genes (e.g. the 5-hydroxytryptamine (5-HT) type 2a receptor (5-HT2a) gene and the dopamine D-3 receptor gene) and as yet unidentified factors localized to specific chromosomal regions, including 6p, 6q, 8p, 13q and 22q, These data provide suggestive, but no conclusive, evidence for causative genes. 3. To enable further progress there is a need to: (i) collect fine-grained clinical datasets while searching the schizophrenia phenotype for subgroups or dimensions that may provide a more direct route to causative genes; and (ii) integrate recent refinements in molecular genetic technology, including modern composite marker maps, DNA expression assays and relevant animal models, while using the latest analytical techniques to extract maximum information in order to help distinguish a true result from a false-positive finding.

Working memory correlates of three symptom clusters in schizophrenia

This study was designed to examine whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. Symptom dimension ratings were assigned to 52 outpatients with schizophrenia (ICD-10 criteria), using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them Simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. Severity of positive symptoms was uncorrelated with performance on any of the measures examined. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Maintaining and updating semantic context in schizophrenia: an investigation of the effects of multiple remote primes

Conflicting findings regarding the ability of people with schizophrenia to maintain and update semantic contexts have been due, arguably, to vagaries within the experimental design employed (e.g. whether strongly or remotely associated prime-target pairs have been used, what delay between the prime and the target was employed, and what proportion of related prime-target pairs appeared) or to characteristics of the participant cohort (e.g. medication status, chronicity of illness). The aim of the present study was to examine how people with schizophrenia maintain and update contextual information over an extended temporal window by using multiple primes that were either remotely associated or unrelated to the target. Fourteen participants with schizophrenia and 12 healthy matched controls were compared across two stimulus onset asynchronies (SOAs) (short and long) and two relatedness proportions (RP) (high and low) in a crossed design. Analysis of variance statistics revealed significant two- and three-way interactions between Group and SOA, Group and Condition, SOA and RP, and Group, SOA and RP. The participants with schizophrenia showed evidence of enhanced remote priming at the short SOA and low RP, combined with a reduction in the time course over which context could be maintained. There was some sensitivity to biasing contextual information at the short SOA, although the mechanism over which context served to update information appeared to be different from that in the controls. The participants with schizophrenia showed marked performance decrements at the long SOA (both low and high RP). Indices of remote priming at the short (but not the long) SOA correlated with both clinical ratings of thought disorder and with increasing length of illness. The results support and extend the hypothesis that schizophrenia is associated with concurrent increases in tonic dopamine activity and decreases in phasic dopamine activity. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Enhancing experiential learning via virtual environments

Research indicates Virtual Reality (VR) is delivering on it's promised potential to provide enhanced training and education outcomes. A significant research project, at the University of Queensland, has constructed a number of virtual contexts in which the phenomena experienced by patients who have psychosis are reproduced for use in psychiatry education. Symptoms of psychosis reproduced include delusions, hallucinations and thought disorder. The new software enables psychiatry students to experience the inner world of a patient with psychosis. Lecturers in psychiatry report VR has the potential to enhance student's abilities to actually 'feel' the types of emotions and physiological reactions a hallucination precipitates in a patient. The current work of the project and stages of software development will be demonstrated. The virtual environments provide a new method of delivering experiential learning opportunities to higher education classrooms.

Functional MR Imaging of visuo-spatial network in Autism Spectrum Disorder

Individuals with Autism Spectrum Disorder (ASD) are generally thought to have impaired attentional and executive function upon which all their cognitive and behaviour functions are based. Mental Rotation is a recognized visuo-spatial task, involving spatial working memory, known to involve activation in the fronto-parietal networks. To elucidate the functioning of fronto-parietal networks in ASD, the aim of this study was to use fMRI techniques with a mental rotation task, to characterize the underlying functional neural system. Sixteen male participants (seven highfunctioning autism or Asperger's syndrome; nine ageand performance IQ-matched controls) underwent fMRI. Participants were presented with 18 baseline and 18 rotation trials, with stimuli rotated 3- dimensionaUy (45°-180°). Data were acquired on a 3- Tesla scanner. The most widely accepted area reported to be involved in processing of visuo-spatial information. Posterior Parietal Cortex, was found to be activated in both groups, however, the ASD group showed decreased activation in cortical and subcortical frontal structures that are highly interconnected, including lateral and medial Brodmann area 6, frontal eye fields, caudate, dorsolateral prefrontal cortex and anterior cingulate. The suggested connectivity between these regions indicates that one or more circuits are impaired as a result of the disorder. In future it is hoped that we are able to identify the possible point of origin of this dysfunction, or indeed if the entire network is dysfunctional.

Blunted growth hormone response to clonidine in post-traumatic stress disorder

Hyperactivity of the sympathetic and noradrenergic systems is thought to be a feature of post-traumatic stress disorder (PTSD). Assessment of noradrenergic receptor function can be undertaken by measuring the growth hormone (GH) response to the alpha(2)-agonist clonidine. The aim of this study was to examine whether subjects with combat-related PTSD (with or without co-morbid depression) have a blunted growth hormone response to clonidine, compared to a combat-exposed control group. Twenty-three Vietnam veterans suffering from PTSD alone, 27 suffering from PTSD and co-morbid depression, and 32 veteran controls with no psychiatric illness were administered 1.5 mug/kg clonidine i.v. Plasma growth hormone was measured every 20 min for 120 min. The growth hormone response to clonidine was significantly blunted in the non-depressed PTSD group compared to both the depressed PTSD group and the control group as measured by peak growth hormone, delta growth hormone and AUC growth hormone. Subjects with PTSD and no co-morbid depressive illness show a blunted growth hormone response to clonidine. This suggests that post-synaptic alpha(2)-receptors are subsensitive. This finding is consistent with other studies showing increased noradrenergic activity in PTSD. (C) 2003 Elsevier Ltd. All rights reserved.

Glucocorticoid receptor polymorphisms and post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is reported in some studies to be associated with increased glucocorticoid (GC) sensitivity. Two common glucocorticoid receptor (GR) potymorphisms (N363S and 8cll) appear to contribute to the population variance in GC sensitivity. There is some evidence that there may be a genetic predisposition to PTSD. Hence we studied 118 Vietnam war veterans with PTSD for (i) GR polymorphisms, particularly the N363S and the Bcll polymorphisms which are thought to be GC sensitising, and (ii) two measures of GC sensitivity, the tow-dose 0.25 mg dexamethasone suppression test (LD-DST) and the dermal vasoconstrictor assay (DVVA). The DST and GR polymorphisms were also performed in 42 combat exposed Vietnam war veterans without PTSD. Basal plasma cortisol levels were not significantly different in PTSD (399.5 +/- 19.2 nmol/L, N=75) and controls (348.6 +/- 23.0 nmol/L, N = 33) and the LD-DST resulted in similar cortisol suppression in both groups (45.6 +/- 3.2 vs. 40.8 +/- 4.1%). The cortisol suppression in PTSD patients does not correlate with Clinician Administered PTSD Scores (CAPS), however there was a significant association between the Bcll GG genotype and low basal cortisol levels in PTSD (P=0.048). The response to the DVVA was similar to controls (945 +/- 122, N = 106 vs. 730 +/- 236, N = 28, P = 0.42). PTSD patients with the GG genotype, however, tended to be more responsive to DVVA and in this group the DVVA correlated with higher CAPS scores. The only exon 2 GR polymorphisms detected were the R23K and N363S. Heterozygosity for the N363S variant in PTSD, at 5.1% was not more prevalent than in other population studies of the N363S polymorphism in Caucasians (6.0-14.8%). The GG genotype of the Bcll polymorphism found to be associated with increased GC sensitivity in many studies showed a tendency towards increased response with DVVA and correlated with higher CAPS scores. In conclusion, the N363S and Bcll GR polymorphisms were not more frequent in PTSD patients than controls and reported population frequencies. Our PTSD group did not display GC hypersensitivity, as measured by the LD-DST and DVVA. In a subset of PTSD patients with the Bcll GG genotype, CAPS scores and basal cortisol Levels were negatively correlated. (C) 2004 Elsevier Ltd. All rights reserved.

Obsessive-compulsive disorder across developmental trajectory: Cognitive processing of threat in children, adolescents and adults

Background. While the cognitive theory of obsessive-compulsive disorder (OCD) is one of the most widely accepted accounts of the maintenance of the disorder in adults, no study to date has systematically evaluated the theory across children, adolescence and adults with OCD. Method. This paper investigated developmental differences in the cognitive processing of threat in a sample of children, adolescents and adults with OCD. Using an idiographic assessment approach, as well as self-report questionnaires, this study evaluated cognitive appraisals of responsibility, probability, severity, thought-action fusion (TAF), thought-suppression, self-doubt and cognitive control. It was hypothesised that there would be age related differences in reported responsibility for harm, probability of harm, severity of harm, thought suppression, TAR self-doubt and cognitive control. Results. Results of this study demonstrated that children with OCD reported experiencing fewer intrusive thoughts, which were less distressing and less uncontrollable than those experienced by adolescents and adults with OCD. Furthermore, responsibility attitudes, probability biases and thought suppression strategies were higher in adolescents and adults with OCD. Cognitive processes of TAF, perceived severity of harm, self-doubt and cognitive control were found to be comparable across age groups. Conclusions. These results suggest that the current cognitive theory of OCD needs to address developmental differences in the cognitive processing of threat. Furthermore, for a developmentally sensitive theory of OCD, further investigation is warranted into other possible age related maintenance factors. Implications of this investigation and directions for future research are discussed.

Serious criminal offending and mental disorder - Case linkage study

Background A relationship exists between mental disorder and offending behaviours but the nature and extent of the association remains in doubt. Method Those convicted in the higher courts of Victoria between 1993 and 1995 had their pyschiatric history explored by case linkage to a register listing virtually all contacts with the public psychiatric services. Results Prior psychiatric contact was found in 25% or offenders, but the personality disorder and substance misuse accounted for much of this relationship. Schizophrenia and affective disorders were also over-represented, particularly those with coexisting substance misuse. Conclusions The increased offending in schizophrenia and affective illness is modest and may often be mediated by coexisting substance misuse. The risk of a serious crime being committed by someone with a major mental illness is small and does not justify subjecting them, as a group, to either increased institutional containment or greater coercion.

Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice

Previously we described activating mutations of h beta(c), the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, h beta(c)FI Delta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the h beta(c)FI Delta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in h beta(c) may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic h beta(c) activation has the potential to contribute to pathological events in the central nervous system.

Effect of disorder on quantum phase transitions in anisotropic XY spin chains in a transverse field

We present some exact results for the effect of disorder on the critical properties of an anisotropic XY spin chain in a transverse held. The continuum limit of the corresponding fermion model is taken and in various cases results in a Dirac equation with a random mass. Exact analytic techniques can then be used to evaluate the density of states and the localization length. In the presence of disorder the ferromagnetic-paramagnetic or Ising transition of the model is in the same universality class as the random transverse field Ising model solved by Fisher using a real-space renormalization-group decimation technique (RSRGDT). If there is only randomness in the anisotropy of the magnetic exchange then the anisotropy transition (from a ferromagnet in the x direction to a ferromagnet in the y direction) is also in this universality class. However, if there is randomness in the isotropic part of the exchange or in the transverse held then in a nonzero transverse field the anisotropy transition is destroyed by the disorder. We show that in the Griffiths' phase near the Ising transition that the ground-state energy has an essential singularity. The results obtained for the dynamical critical exponent, typical correlation length, and for the temperature dependence of the specific heat near the Ising transition agree with the results of the RSRODT and numerical work. [S0163-1829(99)07125-8].