Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis

Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling “deficit schizophrenia.” The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies.

French version of the Family Attitude Scale : psychometric properties and relation of attitudes to the respondent's psychiatric status

The Family Attitude Scale (FAS) is a self-report measure of critical or hostile attitudes and behaviors towards another family member, and demonstrates an ability to predict relapse in psychoses. Data are not currently available on a French version of the scale. The present study developed a French version of the FAS, using a large general population sample to test its internal structure, criterion validity and relationships with the respondents' symptoms and psychiatric diagnoses, and examined the reciprocity of FAS ratings by respondents and their partners. A total of 2072 adults from an urban population undertook a diagnostic interview and completed self-report measures, including an FAS about their partner. A subset of participants had partners who also completed the FAS. Confirmatory factor analyses revealed an excellent fit by a single-factor model, and the FAS demonstrated a strong association with dyadic adjustment. FAS scores of respondents were affected by their anxiety levels and mood, alcohol and anxiety diagnoses, and moderate reciprocity of attitudes and behaviors between the partners was seen. The French version of the FAS has similarly strong psychometric properties to the original English version. Future research should assess the ability of the French FAS to predict relapse of psychiatric disorders.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Cortisol and dehydroepiandrosterone-sulphate levels correlate with symptom severity in first-episode psychosis

Dehydroepiandrosterone (DHEA) and its sulphate form (DHEA) are neuroactive steroids with antiglucocorticoid properties. An imbalance in the ratio of cortisol to DHEA(S) has been implicated in the pathophysiology of stress-related psychiatric disorders. This study prospectively investigated circulating cortisol, DHEAS and their ratio in first-episode psychosis (FEP) patients compared to healthy controls, and their relationship to perceived stress, psychotic, negative and mood symptoms. METHODS: Blood cortisol and DHEAS levels were obtained in 39 neuroleptic-naïve or minimally-treated FEP patients and 25 controls. Twenty-three patients and 15 controls received repeat assessments after 12 weeks. Perceived stress was assessed using the Perceived Stress Scale and symptoms were assessed in patients using standard rating scales. RESULTS: At baseline, no differences were observed in cortisol, DHEAS or the cortisol/DHEAS ratio between patients and controls. There were also no group differences in the change in these biological variables during the study period. Within FEP patients, decreases in cortisol and the cortisol/DHEAS ratio over time were directly related to the improvement in depression (r = 0.45; p = 0.031, r = 0.52; p = 0.01), negative (r = 0.51; p = 0.006, r = 0.55; p = 0.008) and psychotic symptoms (cortisol only, r = 0.53; p = 0.01). Perceived stress significantly correlated with DHEAS (r = 0.51; p = 0.019) and the cortisol/DHEAS ratio (r = -0.49; p = 0.024) in controls, but not patients, possibly reflecting an impaired hormonal response to stress in FEP patients. CONCLUSIONS: These findings further support the involvement of the stress system in the pathophysiology of psychotic disorders, with implications for treatment strategies that modulate these neurosteroids.

How well are Australian children doing in the first year of school : a demographic analysis

Background: The transition to school is a sensitive period for children in relation to school success. In the early school years, children need to develop positive attitudes to school and have experiences that promote academic, behavioural and social competence. When children begin school there are higher expectations of responsibility and independence and in the year one class, there are more explicit academic goals for literacy and numeracy and more formal instruction. Most importantly, children’s early attitudes to learning and learning styles have an impact on later educational outcomes. Method: Data were drawn from The Longitudinal Study of Australian Children (LSAC). LSAC is a cross-sequential cohort study funded by the Australian Government. In these analyses, Wave 2 (2006) data for 2499 children in the Kindergarten Cohort were used. Children, at Wave 2, were in the first year of formal school. They had a mean age of 6.9 years (SD= 0.26). Measures included a 6-item measure of Approaches to Learning (task persistence, independence) and the Academic Rating Scales for language and literacy and mathematical thinking. Teachers rated their relationships with children on the short form of the STRS. Results: Girls were rated by their teachers as doing better than boys on Language and literacy, Approaches to learning; and they had a better relationship with their teacher. Children from an Aboriginal or Torres Strait Island (ATSI) background were rated as doing less well on Language and Literacy and Mathematical thinking and on their Approaches to learning. Children from high Socio Economic Position families are doing better on teacher rated Language and Literacy, Mathematical thinking, Approaches to learning and they had a better relationship with their teacher. Conclusions: Findings highlight the importance of key demographic variables in understanding children’s early school success.

How well are Australian children doing in the first year of school?

Background: The transition to school is a sensitive period for children in relation to school success. In the early school years, children need to develop positive attitudes to school and have experiences that promote academic, behavioural and social competence. When children begin school there are higher expectations of responsibility and independence and in the year one class, there are more explicit academic goals for literacy and numeracy and more formal instruction. Most importantly, children’s early attitudes to learning and learning styles have an impact on later educational outcomes. Method: Data were drawn from The Longitudinal Study of Australian Children (LSAC). LSAC is a cross-sequential cohort study funded by the Australian Government. In these analyses, Wave 2 (2006) data for 2499 children in the Kindergarten Cohort were used. Children, at Wave 2, were in the first year of formal school. They had a mean age of 6.9 years (SD= 0.26). Measures included a 6-item measure of Approaches to Learning (task persistence, independence) and the Academic Rating Scales for language and literacy and mathematical thinking. Teachers rated their relationships with children on the short form of the STRS. Results: Girls were rated by their teachers as doing better than boys on Language and literacy, Approaches to learning; and they had a better relationship with their teacher. Children from an Aboriginal or Torres Strait Island (ATSI) background were rated as doing less well on Language and Literacy and Mathematical thinking and on their Approaches to learning. Children from high Socio Economic Position families are doing better on teacher rated Language and Literacy, Mathematical thinking, Approaches to learning and they had a better relationship with their teacher. Conclusions: Findings highlight the importance of key demographic variables in understanding children’s early school success.

Evaluation of on-road driving in people with hemianopia and quadrantanopia

OBJECTIVE: To examine whether some drivers with hemianopia or quadrantanopia display safe driving skills on the road compared with drivers with normal visual fields. ---------- METHOD: An occupational therapist evaluated 22 people with hemianopia, 8 with quadrantanopia, and 30 with normal vision for driving skills during naturalistic driving using six rating scales. ---------- RESULTS: Of drivers with normal vision, >90% drove flawlessly or had minor errors. Although drivers with hemianopia were more likely to receive poorer ratings for all skills, 59.1%–81.8% performed with no or minor errors. A skill commonly problematic for them was lane keeping (40.9%). Of 8 drivers with quadrantanopia, 7 (87.5%) exhibited no or minor errors. ---------- CONCLUSION: This study of people with hemianopia or quadrantanopia with no lateral spatial neglect highlights the need to provide individual opportunities for on-road driving evaluation under natural traffic conditions if a person is motivated to return to driving after brain injury.

Interactional competence in a paired speaking test : features salient to raters

Paired speaking tests are now commonly used in both high-stakes testing and classroom assessment contexts. The co-construction of discourse by candidates is regarded as a strength of paired speaking tests, as candidates have the opportunity to display a wider range of interactional competencies, including turn taking, initiating topics and engaging in extended discourse with a partner, rather than an examiner. However, the impact of the interlocutor in such jointly negotiated discourse and the implications for assessing interactional competence are areas of concern. This article reports on the features of interactional competence that were salient to four trained raters of 12 paired speaking tests through the analysis of rater notes, stimulated verbal recalls and rater discussions. Findings enabled the identification of features of the performance noted by raters when awarding scores for interactional competence, and the particular features associated with higher and lower scores. A number of these features were seen by the raters as mutual achievements, which raises the issue of the extent to which it is possible to assess individual contributions to the co-constructed performance. The findings have implications for defining the construct of interactional competence in paired speaking tests and operationalising this in rating scales.

Product labelling can confer sustained increases in expected and actual satiety

Expected satiety has been shown to play a key role in decisions around meal size. Recently it has become clear that these expectations can also influence the satiety that is experienced after a food has been consumed. As such, increasing the expected and actual satiety a food product confers without increasing its caloric content is of importance. In this study we sought to determine whether this could be achieved via product labelling. Female participants (N=75) were given a 223-kcal yoghurt smoothie for lunch. In separate conditions the smoothie was labelled as a diet brand, a highly-satiating brand, or an ‘own brand’ control. Expected satiety was assessed using rating scales and a computer-based ‘method of adjustment’, both prior to consuming the smoothie and 24 hours later. Hunger and fullness were assessed at baseline, immediately after consuming the smoothie, and for a further three hours. Despite the fact that all participants consumed the same food, the smoothie branded as highly-satiating was consistently expected to deliver more satiety than the other ‘brands’; this difference was sustained 24 hours after consumption. Furthermore, post-consumption and over three hours, participants consuming this smoothie reported significantly less hunger and significantly greater fullness. These findings demonstrate that the satiety that a product confers depends in part on information that is present around the time of consumption. We suspect that this process is mediated by changes to expected satiety. These effects may potentially be utilised in the development of successful weight-management products.

An introduction to the application of (case 1) best–worst scaling in marketing research

We review and discuss recent developments in best–worst scaling (BWS) that allow researchers to measure items or objects on measurement scales with known properties. We note that BWS has some distinct advantages compared with other measurement approaches, such as category rating scales or paired comparisons. We demonstrate how to use BWS to measure subjective quantities in two different empirical examples. One of these measures preferences for weekend getaways and requires comparing relatively few objects; a second measures academics' perceptions of the quality of academic marketing journals and requires comparing a significantly large set of objects. We conclude by discussing some limitations and future research opportunities related to BWS.

Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Spectrum of ankylosing spondylitis in Portugal. Development of BASDAI, BASFI, BASMI and mSASSS reference centile charts

The availability of population-specific normative data regarding disease severity measures is essential for patient assessment. The goals of the current study were to characterize the pattern of ankylosing spondylitis (AS) in Portuguese patients and to develop reference centile charts for BASDAI, BASFI, BASMI and mSASSS, the most widely used assessment tools in AS. AS cases were recruited from hospital outpatient clinics, with AS defined according to the modified New York criteria. Demographic and clinical data were recorded. All radiographs were evaluated by two independent experienced readers. Centile charts for BASDAI, BASFI, BASMI and mSASSS were constructed for both genders, using generalized linear models and regression models with duration of disease as independent variable. A total of 369 patients (62.3% male, mean ± (SD) age 45.4 ± 13.2 years, mean ± (SD) disease duration 11.4 ± 10.5 years, 70.7% B27-positive) were included. Family history of AS in a first-degree relative was reported in 17.6% of the cases. Regarding clinical disease pattern, at the time of assessment 42.3% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopatic disease. Anterior uveitis (33.6%) was the most common extra-articular manifestation. The centile charts suggest that females reported greater disease activity and more functional impairment than males but had lower BASMI and mSASSS scores. Data collected through this study provided a demographic and clinical profile of patients with AS in Portugal. The development of centile charts constitutes a useful tool to assess the change of disease pattern over time and in response to therapeutic interventions.

The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized stsytems for temporal tracking of appetite ratings.

This present paper reviews the reliability and validity of visual analogue scales (VAS) in terms of (1) their ability to predict feeding behaviour, (2) their sensitivity to experimental manipulations, and (3) their reproducibility. VAS correlate with, but do not reliably predict, energy intake to the extent that they could be used as a proxy of energy intake. They do predict meal initiation in subjects eating their normal diets in their normal environment. Under laboratory conditions, subjectively rated motivation to eat using VAS is sensitive to experimental manipulations and has been found to be reproducible in relation to those experimental regimens. Other work has found them not to be reproducible in relation to repeated protocols. On balance, it would appear, in as much as it is possible to quantify, that VAS exhibit a good degree of within-subject reliability and validity in that they predict with reasonable certainty, meal initiation and amount eaten, and are sensitive to experimental manipulations. This reliability and validity appears more pronounced under the controlled (but more arti®cial) conditions of the laboratory where the signal : noise ratio in experiments appears to be elevated relative to real life. It appears that VAS are best used in within-subject, repeated-measures designs where the effect of different treatments can be compared under similar circumstances. They are best used in conjunction with other measures (e.g. feeding behaviour, changes in plasma metabolites) rather than as proxies for these variables. New hand-held electronic appetite rating systems (EARS) have been developed to increase reliability of data capture and decrease investigator workload. Recent studies have compared these with traditional pen and paper (P&P) VAS. The EARS have been found to be sensitive to experimental manipulations and reproducible relative to P&P. However, subjects appear to exhibit a signi®cantly more constrained use of the scale when using the EARS relative to the P&P. For this reason it is recommended that the two techniques are not used interchangeably

Unraveling the complexity of driving while intoxicated: a study into the prevalence of psychiatric and substance abuse comorbidity

Objective Research is beginning to provide an indication of the co-occurring substance abuse and mental health needs for the driving under the influence (DUI) population. This study aimed to examine the extent of such psychiatric problems among a large sample size of DUI offenders entering treatment in Texas. Methods This is a study of 36,373 past year DUI clients and 308,714 non-past year DUI clients admitted to Texas treatment programs between 2005 and 2008. Data were obtained from the State's administrative dataset. Results Analysis indicated that non-past year DUI clients were more likely to present with more severe illicit substance use problems, while past year DUI clients were more likely to have a primary problem with alcohol. Nevertheless, a cannabis use problem was also found to be significantly associated with DUI recidivism in the last year. In regards to mental health status, a major finding was that depression was the most common psychiatric condition reported by DUI clients, including those with more than one DUI offence in the past year. This cohort also reported elevated levels of Bipolar Disorder compared to the general population, and such a diagnosis was also associated with an increased likelihood of not completing treatment. Additionally, female clients were more likely to be diagnosed with mental health problems than males, as well as more likely to be placed on medications at admission and more likely to have problems with methamphetamine, cocaine, and opiates. Conclusions DUI offenders are at an increased risk of experiencing comorbid psychiatric disorders, and thus, corresponding treatment programs need to cater for a range of mental health concerns that are likely to affect recidivism rates.