Associations between the LEP -2548G/A Promoter and Baseline Weight and between LEPR Gln223Arg and Lys656Asn Variants and Change in BMI z Scores in Arab Children and Adolescents Treated with Risperidone.

Data on baseline (antipsychotics-naïve) age, weight, and height, and change in these at 3 subsequent follow-up time points up to 313.6 days (95% CI 303.5-323.7) were collected from 181 risperidone-treated children and adolescents (mean age 12.58 years, SD 4.99, range 2.17-17.7) attending a pediatric neurology clinic in Saudi Arabia. Owing to differences in genotypic distributions in the subsamples, results are reported for the white Arab population (n = 144). Age- and gender-normed body mass index (BMI)-standardized z scores (BMI z) were calculated (LMSgrowth program). Linear regression was performed for baseline weight and BMI z, while change in BMI z was assessed using random effects ordered logistic regression. The following single nucleotide polymorphisms (SNPs) were analyzed: rs7799039 in the LEP promoter, rs1805094 (previously rs8179183), rs1137100 and rs1137101 in the LEPR, and rs1414334 in HTR2C. We found a nominally significant association between rs7799309 and baseline weight, adjusting for height, age, gender, and diagnosis (A/G, p = 0.035, ß = -3.62 vs. G/G). The rs1137101 (G/G, p = 0.018, odds ratio [OR] = 4.13 vs. A/A) and rs1805094 C allele carriers (p = 0.019, OR = 0.51) showed nominally significant associations with change in BMI z categories. Our data support and replicate previous relevant associations for these variants (including with weight gain when on risperidone), whilst being the first report of such associations in patients of Arab ethnicity.

A qualitative study exploring the experience of people with IBD and elevated symptoms of anxiety and low mood and the type of psychological help they would like.

BACKGROUND: People with inflammatory bowel disease (IBD) are at increased risk of developing anxiety and low mood. We sought to explore the experience of people with IBD and moderate-severe symptoms of anxiety/low mood to identify psychological processes which could be targeted in psychological interventions, as well as the kind of psychological support preferred. METHODS: Twenty-five participants with IBD and moderate-severe symptoms of anxiety/low mood were recruited for interview. Template analysis was utilised to analyse interview data. We explored the situations, cognitions and behaviour linked to symptoms of anxiety and low mood by people with IBD, as well as the kind of psychological help preferred. RESULTS: Two themes were identified within participants accounts of symptoms of anxiety; 'under performance' and 'preventing an accident'. Two further themes were identified for symptoms of low mood; 'lack of understanding' and 'stigma'. Expertise and understanding was the main theme identified for the type of psychological help desired. CONCLUSION: The analysis highlights situations, cognitions and behaviour linked to anxiety and low mood by people with IBD and the type of psychological support desired. Our findings link to the knowledge and competencies set for psychological therapist working with long-term conditions.

Randomised controlled trial to improve health and reduce substance use in established psychosis (IMPaCT): cost-effectiveness of integrated psychosocial health promotion.

BACKGROUND: There is mounting evidence that people with severe mental illness have unhealthy lifestyles, high rates of cardiovascular and metabolic diseases, and greater risk of early mortality. This study aimed to assess the cost-effectiveness of a health promotion intervention seeking to improve physical health and reduce substance use in people with psychosis. METHODS: Participants with a psychotic disorder, aged 18-65 years old and registered on an enhanced care approach programme or equivalent were recruited from community mental health teams in six mental health trusts in England. Participants were randomisation to either standard community mental health team care (treatment as usual) or treatment as usual with an integrated health promotion intervention (IMPaCT). Cost-effectiveness and cost-utility analyses from health and social care and societal perspectives were conducted alongside a cluster randomised controlled trial. Total health and social care costs and total societal costs at 12 and 15 months were calculated as well as cost-effectiveness (incremental cost-effectiveness ratios and cost-effectiveness acceptability curves) at 15 months based on quality of life (SF-36 mental and physical health components, primary outcome measures) and quality adjusted life years (QALYs) using two measures, EQ-5D-3 L and SF-36. Data were analysed using bootstrapped regressions with covariates for relevant baseline variables. RESULTS: At 12-15 months 301 participants had full data needed to be included in the economic evaluation. There were no differences in adjusted health and social care costs (£95, 95% CI -£1410 to £1599) or societal costs (£675, 95% CI -£1039 to £2388) between the intervention and control arms. Similarly, there were no differences between the groups in the SF-36 mental component (-0.80, 95% CI -3.66 to 2.06), SF-36 physical component (-0.68, 95% CI -3.01 to 1.65), QALYs estimated from the SF-36 (-0.00, -0.01 to 0.00) or QALYs estimated from the EQ-5D-3 L (0.00, 95% CI -0.01 to 0.02). Cost-effectiveness acceptability curves for all four outcomes and from both cost perspectives indicate that the probability of the health promotion intervention being cost-effective does not exceed 0.4 for willingness to pay thresholds ranging from £0-£50,000. CONCLUSIONS: Alongside no evidence of additional quality of life/clinical benefit, there is also no evidence of cost-effectiveness. TRIAL REGISTRATION: ISRCTN58667926 . Date retrospectively registered: 23/04/2010. Recruitment start date: 01/03/2010.

Influences on uptake of cancer screening in mental health service users: a qualitative study.

BACKGROUND: Cancers are a leading cause of death worldwide. People with mental illness are 30 % more likely to die from cancer than the general population. One reason for this may be low uptake of nationally offered cancer screening tests by people with mental illness. We aimed to identify barriers and facilitators for breast, cervical and bowel cancer screening uptake by people with mental illness in order to inform interventions to promote equal access. METHODS: The interview study was conducted in both urban and rural settings. The study was informed by the Theoretical Domains Framework, using framework analysis and triangulation across participant groups. Participants included 45 mental health service users (service users) eligible for cancer screening, 29 mental health professionals and 11 professionals involved in cancer screening. RESULTS: Themes emerging from the data that affected uptake included knowledge of screening programmes by both service users and healthcare providers; knowledge of, and attitudes towards, mental illness; health service-delivery factors; service users' beliefs and concerns about cancer screening, and practical issues. These are relevant to different stages of the screening process. Service users do not receive invitations to screening or cancer testing kits if they are admitted to hospital. They are not routinely invited for screening if they are not registered with a general practitioner (GP). Lack of integrated care means that mental health staff do not know if someone is overdue for a test and cancer screening is often not considered during health promotion. Barriers including information processing problems, the extent to which the screening process aggravates symptoms, poor staff client relationships and travel difficulties vary between individuals. Screening professionals are motivated to help, but may lack time or training to manage mental health needs. Reactive measures are available, but service users must request help which they may find difficult. CONCLUSIONS: There are specific barriers to cancer screening uptake for mental health service users that prevent equality of care. Interventions that can be personalised are needed at individual, policy and service-delivery levels. Primary and secondary care staff and policy-makers should work together to develop an integrated approach to cancer screening in this population.

A model of memory impairment in schizophrenia: cognitive and clinical factors associated with memory efficiency and memory errors.

BACKGROUND: Memory impairments in patients with schizophrenia have been associated with various cognitive and clinical factors. Hallucinations have been more specifically associated with errors stemming from source monitoring failure. METHODS: We conducted a broad investigation of verbal memory and visual memory as well as source memory functioning in a sample of patients with schizophrenia. Various memory measures were tallied, and we studied their associations with processing speed, working memory span, and positive, negative, and depressive symptoms. RESULTS: Superficial and deep memory processes were differentially associated with processing speed, working memory span, avolition, depression, and attention disorders. Auditory/verbal and visual hallucinations were differentially associated with specific types of source memory error. CONCLUSIONS: We integrated all the results into a revised version of a previously published model of memory functioning in schizophrenia. The model describes the factors that affect memory efficiency, as well as the cognitive underpinnings of hallucinations within the source monitoring framework.

Serial and semantic encoding of lists of words in schizophrenia patients with visual hallucinations.

Previous research has suggested that visual hallucinations in schizophrenia are associated with abnormal salience of visual mental images. Since visual imagery is used as a mnemonic strategy to learn lists of words, increased visual imagery might impede the other commonly used strategies of serial and semantic encoding. We had previously published data on the serial and semantic strategies implemented by patients when learning lists of concrete words with different levels of semantic organisation (Brébion et al., 2004). In this paper we present a re-analysis of these data, aiming at investigating the associations between learning strategies and visual hallucinations. Results show that the patients with visual hallucinations presented less serial clustering in the non-organisable list than the other patients. In the semantically organisable list with typical instances, they presented both less serial and less semantic clustering than the other patients. Thus, patients with visual hallucinations demonstrate reduced use of serial and semantic encoding in the lists made up of fairly familiar concrete words, which enable the formation of mental images. Although these results are preliminary, we propose that this different processing of the lists stems from the abnormal salience of the mental images such patients experience from the word stimuli.

Production of atypical category exemplars in patients with schizophrenia.

Previous studies have revealed semantic memory impairments in patients with schizophrenia, and suggested that certain of these impairments were related to thought disorganization. One explanation offered for this is a broadening of the boundaries of semantic categories in schizophrenia. We selected 16 semantic categories, and required a sample of 41 schizophrenia patients and 43 healthy control subjects to produce one exemplar from each category. The typicality of the subjects' responses was rated. The exemplars produced by the patients were on average less typical than those produced by the healthy controls. No significant association between typicality of the response and thought disorganization was revealed in the patient sample. Affective flattening, alogia, and anhedonia were significantly and inversely associated with the typicality score, that is, higher ratings of these symptoms were associated with more typical responses. Our results suggest that a broadening of semantic category boundaries is observed in patients with schizophrenia, but is unrelated to thought disorganization. This semantic abnormality is not a feature of the patients with high ratings of certain negative symptoms.

Visual hallucinations in schizophrenia: confusion between imagination and perception.

OBJECTIVE: An association between hallucinations and reality-monitoring deficit has been repeatedly observed in patients with schizophrenia. Most data concern auditory/verbal hallucinations. The aim of this study was to investigate the association between visual hallucinations and a specific type of reality-monitoring deficit, namely confusion between imagined and perceived pictures. METHOD: Forty-one patients with schizophrenia and 43 healthy control participants completed a reality-monitoring task. Thirty-two items were presented either as written words or as pictures. After the presentation phase, participants had to recognize the target words and pictures among distractors, and then remember their mode of presentation. RESULTS: All groups of participants recognized the pictures better than the words, except the patients with visual hallucinations, who presented the opposite pattern. The participants with visual hallucinations made more misattributions to pictures than did the others, and higher ratings of visual hallucinations were correlated with increased tendency to remember words as pictures. No association with auditory hallucinations was revealed. CONCLUSIONS: Our data suggest that visual hallucinations are associated with confusion between visual mental images and perception.

Visual memory errors in schizophrenic patients with auditory and visual hallucinations.

Hallucinations have been found associated with false detection or false recognition of acoustic/verbal material in several studies. We investigated whether they were also linked with false recognition of pictures. Furthermore, an association between hallucinations and deficits in remembering temporal context was observed in previous research on schizophrenia. We investigated whether the association extends to deficits in remembering spatial context. Forty-one patients with schizophrenia underwent a visual memory task. Sixteen mixed black-and-white and colored pictures were presented at different locations. Participants had to recognize the pictures among distractors, then to recall the spatial context of the presentation of the target pictures. Results showed that auditory hallucinations were associated with poor recognition of the colored pictures. When recognition efficiency and negative symptoms were statistically controlled, auditory hallucinations were also associated with increased response bias toward false recognition of nontarget pictures, and with errors in remembering the spatial context. No associations with visual hallucinations emerged. Anhedonia was associated with response bias, in the direction opposite to that of hallucinations. In conclusion, the association between hallucinations and response bias extends across modalities to picture recognition. The association between hallucinations and temporal context impairment extends to spatial context.

Temporal context discrimination in patients with schizophrenia: associations with auditory hallucinations and negative symptoms.

BACKGROUND: A deficit in remembering the temporal context of events (a type of source memory) has been observed in schizophrenia, and suggested to be associated with positive symptoms. METHODS: In order to investigate memory for temporal context, we administered a list discrimination task to a sample of schizophrenia patients and a sample of healthy controls. Participants were required to learn two lists of mixed high- and low-frequency words separated by 10 min, then to remember whether each word had been presented in the first or in the second list. RESULTS: The number of misattributions to the wrong list was significantly higher in patients than in healthy controls. However, the group difference was eliminated when recall efficiency was covaried. The number of list misattributions was higher in patients with auditory hallucinations than in the other patients, independently of verbal recall efficiency. By contrast, affective flattening and anhedonia were associated with fewer list misattributions of the high-frequency words. CONCLUSIONS: It is suggested that auditory hallucinations are associated with deficit in processing or remembering the temporal context. Conversely, certain negative symptoms are associated with reduced temporal context errors. The possible neural mechanisms involved in temporal context deficit as well as in these specific clinical symptoms are discussed.

Cortical effects of quetiapine in first-episode schizophrenia: a preliminary functional magnetic resonance imaging study.

BACKGROUND: Quetiapine improves both psychotic symptoms and cognitive function in schizophrenia. The neural basis of these actions is poorly understood. METHODS: Three subject groups underwent a single functional magnetic resonance imaging (fMRI) session: drug-naive (n = 7) and quetiapine-treated samples of patients with schizophrenia (n = 8) and a healthy control group (n = 8). The fMRI session included an overt verbal fluency task and a passive auditory stimulation task. RESULTS: In the verbal fluency task, there was significantly increased activation in the left inferior frontal cortex in the quetiapine-treated patients and the healthy control sample compared with the drug-naive sample. During auditory stimulation, the healthy control group and stably treated group produced significantly greater activation in the superior temporal gyrus than the drug-naive sample. CONCLUSIONS: Quetiapine treatment is associated with altered blood oxygen level-dependent responses in both the prefrontal and temporal cortex that cannot be accounted for by improved task performance subsequent to drug treatment.

Clinical effectiveness in first-episode patients.

Managing patients with first-episode schizophrenia is a challenging task for psychiatrists. Early diagnosis and effective intervention are vital to achieving long-term positive clinical outcomes among first-episode patients. Although these patients are the most responsive to treatment, they are also more susceptible to adverse events. The efficacy and improved tolerability associated with the newer atypical antipsychotics means that these drugs can be used successfully in the treatment and long-term management of schizophrenia from the onset of illness. However, as well as managing the symptoms of the disease, pharmacological treatments need to meet the broader requirements of clinical effectiveness that encompass all of the outcome domains associated with schizophrenia. This article will discuss available data on atypical antipsychotics in first-episode patients and present the primary results from the F1RST (Southwark first-onset psychosis) study, which examined the use of quetiapine for the first-line management of schizophrenia as part of a specialist episode psychosis service.