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To evaluate long-term treatment with ziprasidone versus haloperidol (up to 196 weeks), as assessed by PANSS negative score and and its association with quality-of-life (QLS).
The study included two treatment periods: (i) a 40-week, randomized, double-blind phase comparing ziprasidone (ZIP 80-160 mg/d given BID, N=227; ZIP 80-120 mg/d given QD, N=221) versus haloperidol (HAL 5-20 mg/d, N=151), followed by (ii) a 3-year, double-blind extension phase on the same double-blind medications (ZIP BID N=72, ZIP QD N=67, and HAL N=47, respectively). We adapted the Andreasen et al. approach to define negative symptom remission based on attainment of a score ≤3 (mild or less) for at least 6 months on all 7 PANSS negative symptom items. MMRM and GEE models were applied to analyze mean changes in PANSS negative, negative symptom remission rate, and QLS scores over time.
In the 40-week core study, ziprasidone was associated with greater improvement in efficacy and QLS outcomes than haloperidol, but the differences were not statistically significant (p>0.05). However, MMRM analysis of PANSS negative and QLS scores over 196 weeks demonstrated differential treatment effects favoring ziprasidone (80-160 mg/d BID vs. haloperidol) (all p<0.05). Ziprasidone-treated subjects (given BID) were significantly more likely to achieve negative symptom remission (46%) than haloperidol-treated (32%) subjects (p<0.05) during the continuation phase; while ziprasidone given QD (46%) showed a trend to enhanced remission (p<0.08).
These findings support the potential for enhanced social and functional outcomes during long-term treatment with an atypical antipsychotic agent.
The increased prevalence of metabolic syndrome in people with severe mental illness (SMI) is well documented. The International Diabetes Federation (IDF) criteria for metabolic syndrome are three or more of the following: waist circumference ( 80 cm (females), (94 cm (males) OR BMI (30, triglycerides >1.7 mmol/l or on treatment, raised blood pressure (systolic >130 mg Hg or diastolic >85 mm Hg, OR on treatment for hypertension), raised fasting blood glucose (.5.6 mmol/l) OR diagnosed type II diabetes) and reduced HDL cholesterol (< 1.03 mmol/l) OR on treatment.
The IMPACT RCT is a Department of Health funded trial of a health promotion intervention (HPI) delivered by care co-ordinators to people with SMI across South London, Kent and Sussex. The intervention is focussed on improving health by addressing modifiable lifestyle factors such as diet, physical activity, obesity, cigarette smoking, alcohol and substance use.
We investigated the prevalence of metabolic syndrome in a sample of 212 patients for whom we had relevant baseline measures.
Data (weight, BMI, waist circumference, blood pressure, fasting HDL cholesterol, triglycerides and glucose levels) were analysed on 212 patients.
45% of the sample met IDF criteria for metabolic syndrome. Mean BMI was 30.6, glucose 6.4 mmol/L, triglycerides 2.0 mmol/L, HDL 1.2 (mmol/L), waist circumference 105.8 cm, and BP 122/82 mm Hg.
Metabolic syndrome was highly prevalent in this sample, significantly increasing the risk of physical morbidity and potentially lowering life expectancy. There is an unmet need for health promotion interventions in order to lower morbidity and mortality risk in these populations.
The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown.
Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics.
A total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR = 4.825) of developing psychotic disorders, and a reduced risk (HR = 0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P < 0.001).
In the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes.
In the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup.
While incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.
In recent years the association between sexual dysfunction (SD) and obesity in the general population has drawn major attention. Although sexual dysfunction is common in psychosis, its relationship with weight gain and obesity remains unclear.
To investigate the association between sexual dysfunction and obesity in a cohort of patients with first episode psychosis.
Sexual function was assessed in a cohort of patients with first episode psychosis using the Sexual Function Questionnaire (SFQ). Anthropometric measures, including weight, BMI, waist, waist–hip ratio were investigated. Additionally, leptin and testosterone were investigated in male patients.
A total of 116 patients (61 males and 55 females) were included. Of these 59% of males and 67.3% of females showed sexual dysfunction (SD) according to the SFQ. In males, higher SFQ scores were significantly correlated with higher BMI (Std. β = 0.36, P = 0.01), higher leptin levels (Std. β = 0.34, P = 0.02), higher waist–hip ratio (Std. β = 0.32, P = 0.04) and lower testosterone levels (Std. β = −0.44, P = 0.002). In contrast, in females, SFQ scores were not associated with any of these factors.
While sexual dysfunction is present in both female and male patients with their first episode of psychosis, only in males is sexual dysfunction associated with increased BMI and waist–hip ratio. The association between SD, BMI, low levels of testosterone and high levels of leptin suggest that policies that lead to healthier diets and more active lifestyles can be beneficial at least, to male patients.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
This Research Communication describes an investigation of the nutritional depletion of total mixed rations (TMR) by pest birds. We hypothesized that species-specific bird depredation of TMR can alter the nutritional composition of the ration and that these changes can negatively impact the performance of dairy cows. Blackbirds selected the high energy fraction of the TMR (i.e., flaked corn) and reduced starch, crude fat and total digestible nutrients during controlled feeding experiments. For Holsteins producing 37·1 kg of milk/d, dairy production modeling illustrated that total required net energy intake (NEI) was 35·8 Mcal/d. For the reference TMR unexposed to blackbirds and the blackbird-consumed TMR, NEI supplied was 41·2 and 37·8 Mcal/d, and the resulting energy balance was 5·4 and 2·0 Mcal/d, respectively. Thus, Holsteins fed the reference and blackbird-consumed TMR were estimated to gain one body condition score in 96 and 254 d, and experience daily weight change due to reserves of 1·1 and 0·4 kg/d, respectively. We discuss these results in context of an integrated pest management program for mitigating the depredation caused by pest birds at commercial dairies.
We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment.
Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria.
High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS.
In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.
Studies in animals and human subjects indicate that gut-derived bacterial endotoxins may play a critical role in the development of non-alcoholic fatty liver disease (NAFLD). In the present study, we investigated if the liver is also sensitised by other microbial components during the onset of fructose-induced steatosis in a mouse model. C57BL/6 mice were either fed with 30 % fructose solution or tap water (control) with or without antibiotics for 8 weeks. Expression of toll-like receptors (TLR)1–9, TNF-α, inducible NO synthase (iNOS), myeloid differentiation factor 88 (MyD88) and number of F4/80 positive cells in the liver were assessed. Occludin protein, DNA of microbiota in the small and large intestine and retinol binding protein 4 (RBP4) in plasma were analysed using Western blot, DNA fingerprinting and ELISA, respectively. F4/80 positive cells were determined by immunohistochemistry. The accumulation of TAG found in the livers of fructose-fed mice was associated with a significant induction of TLR 1–4 and 6–8. Plasma RBP4 concentration and hepatic mRNA expression levels of TNF-α, iNOS, MyD88 and number of F4/80 positive cells of fructose-fed animals were significantly higher than those of controls; however, these effects of fructose were attenuated in antibiotic-treated mice. Whereas protein concentration of occludin was lower in the duodenum of fructose-treated mice, no systematic alterations of microbiota were found in this part of the intestine. Taken together, these data support the hypothesis that (1) an increased intestinal translocation of microbial components and (2) an increased number of F4/80 positive cells and induction of several TLR and dependent pathways (e.g. MyD88 and iNOS) may be involved in the onset of fructose-induced NAFLD.
In people with bulimic eating disorders, exposure to high-calorie foods can result in increases in food craving, raised subjective stress and salivary cortisol concentrations. This cue-induced food craving can be reduced by repetitive transcranial magnetic stimulation (rTMS). We investigated whether rTMS has a similar effect on salivary cortisol concentrations, a measure of hypothalamic–pituitary–adrenal axis (HPAA) activity.
We enrolled twenty-two female participants who took part in a double-blind randomized sham-controlled trial on the effects of rTMS on food craving. Per group, eleven participants were randomized to the real or sham rTMS condition. The intervention consisted of one session of high-frequency rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC). Salivary cortisol concentrations were assessed at four time points throughout the 90-min trial. To investigate differences in post-rTMS concentrations between the real and sham rTMS groups, a random-effects model including the pre-rTMS cortisol concentrations as covariates was used.
Salivary cortisol concentrations following real rTMS were significantly lower compared with those following sham rTMS. In this sample, there was also a trend for real rTMS to reduce food craving more than sham rTMS.
These results suggest that rTMS applied to the left DLPFC alters HPAA activity in people with a bulimic disorder.
Bulimic eating disorders are common among female students, yet the majority do not access effective treatment. Internet-based cognitive-behavioural therapy (iCBT) may be able to bridge this gap.
Seventy-six students with bulimia nervosa (BN) or eating disorder not otherwise specified (EDNOS) were randomly assigned to immediate iCBT with e-mail support over 3 months or to a 3-month waiting list followed by iCBT [waiting list/delayed treatment control (WL/DTC)]. ED outcomes were assessed with the Eating Disorder Examination (EDE) at baseline, 3 months and 6 months. Other outcomes included depression, anxiety and quality of life.
Students who had immediate iCBT showed significantly greater improvements at 3 and 6 months than those receiving WL/DTC in ED and other symptoms.
iCBT with e-mail support is efficacious in students with bulimic disorders and has lasting effects.
To investigate whether young adults born very preterm (VPT) (<33 weeks) are at increased risk for psychiatric illness in adulthood and whether a family history of psychiatric disorder further increases this risk.
We assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule – Revised.
Young adults born VPT had an increased risk for psychiatric disorder compared to controls (OR = 3.1, 95% CI = 1.1–8.6, p = 0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR = 5.2, 95% CI = 1.8–14.9, p = 0.002).
Individuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.
This review systematically appraised the research evidence for local versus global information processing to test the hypothesis that people with eating disorders (ED) had weak central coherence.
Searches on Medline, EMBASE, PsycINFO and ISI Web of Science databases were conducted in November 2006 and subsequently updated in September 2007. Each search was conducted in two steps: (1) neuropsychological tasks measuring central coherence and (2) words related to cognitive functioning in eating disorders. Data were summarized in a meta-analysis if the number of studies for a given test was >5.
Data were extracted from 16 studies. Meta-analyses were conducted for four tasks obtaining moderate effect sizes. The majority of studies found global processing difficulties across the ED spectrum. The results are less clear regarding local processing.
People with ED have difficulties in global processing. It is less certain as to whether they have superior local processing. Currently, there is insufficient evidence to refute the weak central coherence hypothesis.
A multi-faceted, multi-institutional laboratory astrophysics program is carried out at the Livermore electron beam ion trap facility, which is a mature spectroscopic source with unsurpassed controls and capabilities, and an unparalleled assortment of spectroscopic equipment, including a full complement of grating and crystal spectrometers and a 6x6 micro-calorimeter array. Recent results range from the calibration of x-ray diagnostics, including the Fe XVII and Fe XXV emission lines, extensive lists of L-shell ions, the first laboratory simulation and fit of a cometary x-ray emission spectrum, and the discovery of new spectral diagnostics for measuring magnetic field strengths.