Antipsychotic treatment resistance in first-episode psychosis: prevalence, subtypes and predictors

Background: 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. Method: 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. Results: 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. Conclusions: 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

Factors associated with dental caries among institutionalized residents with schizophrenia in Taiwan: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Little research has been done on the relationship between dental caries and the personal characteristics of institutionalized residents diagnosed with schizophrenia. This study investigates the individual and treatment factors associated with the dental caries among institutionalized residents with schizophrenia in Taiwan.</p> <p>Methods</p> <p>An oral health survey of institutionalized residents with schizophrenia in the largest public psychiatric hospital was conducted in Taiwan in 2006. Based on this data, multiple logistic analyses were used to determine the relationship between some explanatory variables and the outcome variables of dental caries among subjects with schizophrenia.</p> <p>Results</p> <p>Among the 1,108 subjects with schizophrenia, age was the only variable independently associated with DMFT > 8 (OR = 7.74, 95% CI = 3.86-15.55, p < 0.001 in comparison to residents aged 65 + years vs. 20-44 years; OR = 3.06, 95% CI = 2.03-4.61, p < 0.001 in comparison to residents aged 55-64 years vs. 20-44 years) after making adjustments for other explanatory variables. In addition, those with an education of only elementary school (OR = 1.67, 95% CI = 1.08-2.56, p = 0.021), low income (OR = 1.58, 95% CI = 1.02-2.44, p = 0.039), and length of stay (LOS) of > 10 years (OR = 2.09, 95% CI = 1.30-3.37, p = 0.002) were associated with a care index < 54.7%. Older age, lower educational level, and longer hospital stays were associated with number of remaining teeth being < 24.</p> <p>Conclusions</p> <p>Aging was the most important factor related to a high level of dental caries. Low educational level, low income, and LOS were also associated with the indicators of dental caries among institutionalized subjects with schizophrenia. It is necessary to address the treatment factors such as prolonged stay in institutions when decision-makers are planning for preventive strategies of oral health for institutionalized residents with schizophrenia.</p

Using motivational techniques to reduce cardiometabolic risk factors in long term psychiatric inpatients: A naturalistic interventional study

Background People with severe mental illness have markedly reduced life expectancy; cardiometabolic disease is a major cause. Psychiatric hospital inpatients have elevated levels of cardiometabolic risk factors and are to a high degree dependent of the routines and facilities of the institutions. Studies of lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients are few. The current study aimed at assessing the feasibility and effects of a lifestyle intervention including Motivational Interviewing (MI) on physical activity levels, cardiometabolic risk status and mental health status in psychotic disorder inpatients. Methods Prospective naturalistic intervention study of 83 patients at long term inpatient psychosis treatment wards in South-Eastern Norway. Patients were assessed 3–6 months prior to, at start and 6 months after a life-style intervention program including training of staff in MI, simple changes in routines and improvements of facilities for physical exercise. Assessments were done by clinical staff and included level of physical activity, motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as well as anthropometric and biochemical markers of cardiometabolic risk. A mixed model was applied to analyze change over time. Results A total of 88% of patients received MI interventions, with a mean of 2.5 MI interventions per week per patient. The physical activity level was not increased, but activity level was positively associated with motivation and negatively associated with positive symptoms. Triglyceride levels and number of smokers were significantly reduced and a significant decrease in symptom levels was observed. Conclusions The current results suggest that a simple, low cost life-style intervention program focusing on motivational change is feasible and may reduce symptoms and improve lifestyle habits in psychosis patients in long term treatment facilities. Similar programs may easily be implemented in other psychiatric hospitals.submittedVersio

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass

Impact of a nurse-led intervention to improve screening for cardiovascular risk factors in people with severe mental illnesses. Phase-two cluster randomised feasibility trial of community mental health teams

Background: People with severe mental illnesses (SMI) are at increased risk of cardiovascular disease (CVD). Clinical guidelines recommend regular screening for CVD risk factors. We evaluated a nurse led intervention to improve screening rates across the primary-secondary care interface.Methods: Six community mental health teams (CMHTs) were randomised to receive either the nurse led intervention plus education pack (n = 3) or education pack only (n = 3). Intervention (6 months): The nurse promoted CVD screening in primary care and then in CMHTs. Patients who remained unscreened were offered screening by the nurse. After the intervention participants with SMI were recruited from each CMHT to collect outcome data. Main outcome: Numbers screened during the six months, confirmed in General Practice notes.Results: All six CMHTs approached agreed to randomisation. 121 people with SMI participated in outcome interviews during two waves of recruitment (intervention arm n = 59, control arm n = 62). Participants from both arms of the trial had similar demographic profiles and rates of previous CVD screening in the previous year, with less than 20% having been screened for each risk factor. After the trial, CVD screening had increased in both arms but participants from the intervention arm were significantly more likely to have received screening for blood pressure (96% vs 68%; adjusted Odds Ratio (OR) 13.6; 95% CI: 3.5-38.4), cholesterol (66.7% vs 26.9%, OR 6.1; 3.2-11.5), glucose (66.7% vs 36.5% OR 4.4; 2.7-7.1), BMI (92.5% vs 65.2% OR 6.5; 2.1-19.6), and smoking status (88.2% vs 57.8% OR 5.5; 3.2-9.5) and have a 10 year CVD risk score calculated (38.2% vs 10.9%) OR 5.2 1.8-15.3). Within the intervention arm approximately half the screening was performed in general practice and half by the trial nurse.Conclusions: The nurse-led intervention was superior, resulting in an absolute increase of approximately 30% more people with SMI receiving screening for each CVD risk factor. The feasibility of the trial was confirmed in terms of CMHT recruitment and the intervention, but the response rate for outcome collection was disappointing; possibly a result of the cluster design. The trial was not large or long enough to detect changes in risk factors.Trial Registration: International Standard Randomised Controlled Trial Registration Number (ISRCTRN) 58625025

Mineral Composition is Altered by Osteoblast Expression of an Engineered Gs-Coupled Receptor

Activation of the Gs G protein–coupled receptor Rs1 in osteoblasts increases bone mineral density by 5- to 15-fold in mice and recapitulates histologic aspects of fibrous dysplasia of the bone. However, the effects of constitutive Gs signaling on bone tissue quality are not known. The goal of this study was to determine bone tissue quality in mice resulting from osteoblast-specific constitutive Gs activation, by the complementary techniques of FTIR spectroscopy and synchrotron radiation micro-computed tomography (SRμCT). Col1(2.3)-tTA/TetO-Rs1 double transgenic (DT) mice, which showed osteoblast-specific constitutive Gs signaling activity by the Rs1 receptor, were created. Femora and calvariae of DT and wild-type (WT) mice (6 and 15 weeks old) were analyzed by FTIR spectroscopy. WT and DT femora (3 and 9 weeks old) were imaged by SRμCT. Mineral-to-matrix ratio was 25% lower (P = 0.010), carbonate-to-phosphate ratio was 20% higher (P = 0.025), crystallinity was 4% lower (P = 0.004), and cross-link ratio was 11% lower (P = 0.025) in 6-week DT bone. Differences persisted in 15-week animals. Quantitative SRμCT analysis revealed substantial differences in mean values and heterogeneity of tissue mineral density (TMD). TMD values were 1,156 ± 100 and 711 ± 251 mg/cm3 (mean ± SD) in WT and DT femoral diaphyses, respectively, at 3 weeks. Similar differences were found in 9-week animals. These results demonstrate that continuous Gs activation in murine osteoblasts leads to deposition of immature bone tissue with reduced mineralization. Our findings suggest that bone tissue quality may be an important contributor to increased fracture risk in fibrous dysplasia patients

The -1997 G/T and Sp1 Polymorphisms in the Collagen Type I alpha1 (COLIA1) Gene in Relation to Changes in Femoral Neck Bone Mineral Density and the Risk of Fracture in the Elderly: The Rotterdam Study

The COLIA1 Sp1 polymorphism has been associated with bone mineral density (BMD) and fracture. A promoter polymorphism, -1997 G/T, also has been associated with BMD. In this study, we examined whether these polymorphisms alone and in the form of haplotypes influence bone parameters and fracture risk in a large population-based cohort of elderly Caucasians. We determined the COLIA1 -1997 G/T (promoter) and Sp1 G/T (intron) polymorphisms in 6,280 individuals and inferred haplotypes. Femoral neck BMD and BMD change were compared across COLIA1 genotypes at baseline and follow-up (mean 6.5 years). We also investigated the relationship between the COLIA1 polymorphisms and incident nonvertebral fractures, which were recorded during a mean follow-up period of 7.4 years. Vertebral fractures were assessed by radiographs on 3,456 genotyped individuals. Femoral neck BMD measured at baseline was 3.8% lower in women carrying two copies of the T-Sp1 allele (P for trend = 0.03). No genotype dependent differences in BMD loss were observed. In women homozygous for the T allele of the Sp1 polymorphism, the risk of fragility fracture increased 2.3 times (95% confidence interval 1.4–3.9, P = 0.001). No such association was observed with the promoter polymorphism. In men, no association with either the Sp1 or the -1997 G/T promoter polymorphism was seen with BMD or fracture. High linkage disequilibrium (LD; D′ = 0.99, r2 = 0.03) exists between the two studied polymorphisms. We observed three haplotypes in our population: haplotype 1 (Gpromoter–Gintron) frequency (f) = 69%, haplotype 2 (Gpromoter–Tintron) f = 17.6%, and haplotype 3 (Tpromoter–Gintron) f = 13.4%. Haplotype 2 was associated with a 2.1-fold increased risk of fragility fracture in women (95% confidence interval 1.2–3.7, P = 0.001). We confirm that the COLIA1 Sp1 polymorphism influences BMD and the risk of fracture in postmenopausal Caucasian women. In contrast, we found no independent effect of the -1997 G/T promoter polymorphism on BMD or fracture

In Vivo Evaluation of the Presence of Bone Marrow in Cortical Porosity in Postmenopausal Osteopenic Women

This is the first observational study examining cortical porosity in vivo in postmenopausal osteopenic women and to incorporate data from two different imaging modalities to further examine the nature of cortical porosity. The goal of this study was to combine high-resolution peripheral computed tomography (HR-pQCT) images, which contain high spatial resolution information of the cortical structure, and magnetic resonance (MR) images, which allow the visualization of soft tissues such as bone marrow, to observe the amount of cortical porosity that contains bone marrow in postmenopausal osteopenic women. The radius of 49 and the tibia of 51 postmenopausal osteopenic women (age 56 ± 3.7) were scanned using both HR-pQCT and MR imaging. A normalized mutual information registration algorithm was used to obtain a three-dimensional rigid transform which aligned the MR image to the HR-pQCT image. The aligned images allowed for the visualization of bone marrow in cortical pores. From the HR-pQCT image, the percent cortical porosity, the number of cortical pores, and the size of each cortical pore was determined. By overlaying the aligned MR and HR-pQCT images, the percent of cortical pores containing marrow, the number of cortical pores containing marrow, and the size of each cortical pore containing marrow were measured. While the amount of cortical porosity did not vary greatly between subjects, the type of cortical pore, containing marrow vs. not containing marrow, varied highly between subjects. The results suggest that cortical pore spaces contain components of varying composition, and that there may be more than one mechanism for the development of cortical porosity