Home visits in the Danish High Risk and Resilience Study - VIA 7: assessment of the home environment of 508 7-year-old children born to parents diagnosed with schizophrenia or bipolar disorder.

OBJECTIVE: The home environment provided by the caregivers of a child is an influential single factor for development and well-being. We aimed to compare the quality of the home environment of children at familial high risk of schizophrenia or bipolar disorder with population-based controls. METHODS: Danish nationwide registers were used to retrieve a cohort of 522 7-year-old children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) or none of these diagnoses (N = 200). The home environment was assessed using the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory). RESULTS: The proportion of children living in home environments that were evaluated not to meet the needs of a 7-year-old child was significantly larger in the two familial high-risk groups. This was true for 21% of the children with familial predisposition for schizophrenia and 7% of children with familial disposition for bipolar disorder. CONCLUSION: Children born to parents diagnosed with schizophrenia and to a lesser extent bipolar disorder are at an increased risk of growing up in a home environment with an insufficient level of stimulation and support. Identifying families with inadequate home environments is a necessary step towards specialized help and support to at-risk families.

Stability and development of psychotic symptoms and the use of antipsychotic medication - long-term follow-up.

BACKGROUND: Few studies have evaluated the development in the use of antipsychotic medication and psychotic symptoms in patients with first-episode psychosis on a long-term basis. Our objective was to investigate how psychotic symptoms and the use of antipsychotic medication changed over a 10-year period in a cohort of patients with first-episode psychosis. METHOD: The study is a longitudinal prospective cohort study over 10 years with follow-ups at years 1, 2, 5 and 10. A total of 496 patients with first-episode psychosis were included in a multi-centre study initiated between 1998 and 2000 in Copenhagen and Aarhus, Denmark. RESULTS: At all follow-ups, a large proportion (20-30%) of patients had remission of psychotic symptoms without use of antipsychotic medication at the time of the follow-up. Patients who were in this group at the 5-year follow-up had an 87% [95% confidence interval (CI) 77-96%] chance of being in the same group at the 10-year follow-up. This stability was also the case for patients who had psychotic symptoms and were treated with antipsychotic medication at year 5, where there was a 67% (95% CI 56-78%) probability of being in this group at the consecutive follow-up. CONCLUSIONS: A large group of patients with psychotic illness were in remission without the use of antipsychotic medication, peaking at year 10. Overall there was a large degree of stability in disease courses over the 10-year period. These results suggest that the long-term outcome of psychotic illness is heterogeneous and further investigation on a more individualized approach to long-term treatment is needed.

Change in cannabis use, clinical symptoms and social functioning among patients with first-episode psychosis: a 5-year follow-up study of patients in the OPUS trial.

BACKGROUND: Several studies indicate that cannabis use among patients with psychotic disorders is associated with worse outcome, but only a few studies have controlled for baseline condition and medication. METHOD: At 5-year follow-up, interviews were carried out with 314 first-episode psychosis patients included in the OPUS trial. The patients included were in the age range of 18 to 45 years old and 59% were male. Cannabis use was extracted from the Schedule for Clinical Assessment in Neuropsychiatry. At follow-up, the patients were divided into different groups according to the variable cannabis use: abstainers, stoppers, starters and continuers. Psychotic, negative and disorganized dimensions (ranging from zero to five) were calculated for each of the four groups based on the Schedule for the Assessment of Positive and Negative Symptoms in Schizophrenia. RESULTS: Cannabis users were younger (24.6 years v. 27.4 years, p < 0.001) and had a lower level of education. At the 5-year follow-up, users of cannabis had higher scores on the psychotic dimension [difference 0.97, 95% confidence interval (CI) 0.41-1.53, p = 0.001] and lower levels of the Global Assessment of Functioning (difference 8.26, 95% CI 2.13-14.39, p = 0.01). Those who stopped using cannabis between entry and 5-year follow-up had a significantly lower level of psychotic symptoms at 5-year follow-up even after controlling for baseline level of psychotic symptoms and for insufficient antipsychotic medication (adjusted difference in psychotic dimension -1.04, 95% CI -1.77 to -0.31, p = 0.006). CONCLUSIONS: Continuous cannabis use was associated with higher levels of psychotic symptoms after 5 years, and this association was only partly explained by insufficient antipsychotic medication.

Gender differences in first-episode psychosis at 5-year follow-up--two different courses of disease? Results from the OPUS study at 5-year follow-up.

OBJECTIVE: Gender differences in psychosis have been investigated, and the results have contributed to a better understanding of the disease, but many questions are unanswered. In clinical terms, women and men with psychosis differ in terms of access to social support, tendency of substance abuse, level of functioning and symptom patterns. We aimed to investigate how gender differences at onset of psychosis develop during the first 5years of treatment. METHOD: A total of 578 patients with a first-episode psychosis in the schizophrenia spectrum were included in the Danish OPUS trial--a randomized clinical trial comparing 2 years of intensive early-intervention programme with standard treatment. All patients were assessed with validated instruments at inclusion, and after 2 and 5 years. Data were analysed for significant gender differences. RESULTS: Males have significantly higher levels of negative symptoms at all times, and are more likely to live alone and suffer from substance abuse. Females reach higher levels of social functioning at follow-up, and show a greater tendency to be employed or in education than males. Markedly more women than men live with children. More women than men reach a state of recovery and are more compliant with medication. CONCLUSION: There are significant gender differences at 2- and 5-year follow-up in this large cohort of first-episode psychotic patients. Males and females show different symptomatology and different levels of social functioning.

Deinstitutionalization revisited: a 5-year follow-up of a randomized clinical trial of hospital-based rehabilitation versus specialized assertive intervention (OPUS) versus standard treatment for patients with first-episode schizophrenia spectrum disorders.

BACKGROUND: The effects of hospital-based rehabilitation including weekly supportive psychodynamic therapy compared with specialized assertive intervention and standard treatment has not previously been investigated in first-episode psychosis. The aim of the study was to examine long-term effect on use of institutional care of different intensive interventions for patients with first-episode schizophrenia spectrum disorder on use of psychiatric bed days and days in supported housing. METHOD: A total of 94 severely ill patients with first-episode schizophrenia spectrum disorders were included in a special part of the Copenhagen OPUS trial and randomized to either the specialized assertive intervention program (OPUS), standard treatment or hospital-based rehabilitation. RESULTS: It was a stable pattern that patients randomized to hospital-based rehabilitation spent more days in psychiatric wards and in supported housing throughout the 5-year follow-up period compared with the two other groups. Patients in OPUS treatment spent significantly fewer days in psychiatric wards and supported housing in the first 3 years compared with patients in hospital-based rehabilitation. Due to attrition and small sample size, differences in level of psychotic and negative symptoms at 5-year follow-up could not be evaluated. CONCLUSIONS: The study indicates that hospital-based rehabilitation together with weekly supportive psychodynamic therapy was associated with a continued increased use of psychiatric bed days and days in supported housing. The data cannot justify using hospital-based rehabilitation in first-episode psychosis.

The association between pre-morbid adjustment, duration of untreated psychosis and outcome in first-episode psychosis.

BACKGROUND: The association between the duration of untreated psychosis (DUP) and outcome of schizophrenia may be confounded by other factors such as poor pre-morbid adjustment. The aim of the present study was to examine the independent contributions of DUP and of pre-morbid adjustment to the clinical and social outcomes of schizophrenia. METHOD: A longitudinal, prospective, 2-year follow-up study of 423 patients with first-episode schizophrenia-spectrum psychosis was conducted. Patients were comprehensively assessed at entry, 1-year and 2-year follow-up. At entry, DUP was measured by IRAOS (an instrument for the assessment of onset and early course of schizophrenia) and pre-morbid adjustment was measured by the Pre-morbid Adjustment Scale (PAS) as 'pre-morbid social adaptation' and 'pre-morbid school adaptation'. Outcome measures included the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Social Network Schedule and social information. Multiple linear regression models were used for data analysis. RESULTS: The median DUP was 48 weeks, which is long compared to other studies. Longer DUP was independently associated with more psychotic symptoms at entry, 1-year and 2-year follow-up. Poorer pre-morbid social adaptation was independently associated with more negative symptoms and smaller social network at entry and 1-year follow-up. Poorer pre-morbid school adaptation was independently associated with poor vocational outcome at 1-year and 2-year follow-up. CONCLUSIONS: Longer DUP is associated with poorer 2-year outcome of psychosis in schizophrenia-spectrum disorders, when pre-morbid functioning and other prognostic factors are controlled for. Impaired pre-morbid development is independently associated with more negative symptoms and poorer social outcome.

Integrated treatment ameliorates negative symptoms in first episode psychosis--results from the Danish OPUS trial.

PURPOSE: To investigate the effect of integrated treatment on negative, psychotic and disorganised symptoms in patients with first episode psychosis. METHOD: A RCT comparing integrated treatment (IT) with standard treatment (ST) was conducted, including 547 patients, aged 18-45, diagnosed with schizophrenia spectrum disorders. All patients were assessed with SCAN, SAPS and SANS at entry and after 1 and 2 years. The IT consisted of assertive community treatment, multifamily groups, psycho-education and social skills training, and the caseload was 1:10 compared with 1:25 in ST. Since attrition was considerable, a mixed model analysis with repeated measurements was used to examine the possible effects of IT statistically. RESULTS: IT reduced both negative and positive symptoms significantly better than ST. Most marked were the results from the negative dimension, where all five global scores from SANS had a significantly better reduction in IT. Sub-analyses did not single out any one element in the integrated treatment that could explain this result. CONCLUSION: Integrated treatment significantly reduced both negative and psychotic symptoms, assumably due to the different psychosocial treatment elements that were provided in the IT. The results indicate that the integrated approach is crucial, since, most likely, many aspects of the integrated treatment have contributed to the reduction of symptoms.

OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial.

BACKGROUND: Patients with first-episode psychosis comprise a high-risk group in terms of suicide. AIMS: To identify predictive factors for suicidal behaviour and to examine the effect of integrated treatment on suicidal behaviour and hopelessness. METHOD: A total of 341 patients with a first-episode schizophrenia-spectrum disorder were randomised to integrated treatment or treatment as usual. RESULTS: During the 1-year follow-up period, 11% attempted suicide. This was associated with female gender, hopelessness, hallucinations and suicide attempt reported at baseline, with the two latter variables being the only significant ones in the final multivariate model. The integrated treatment reduced hopelessness. CONCLUSIONS: Hallucinations and suicide attempt before inclusion in the study were the most significant predictors of suicide attempt in the follow-up period.

Expression of VLA-integrins and their related basement membrane ligands in gingiva from patients of various periodontitis categories.

Periodontitis is characterized by destruction of dento-gingival fibers and apical migration of the junctional epithelium. Tissue destruction may be associated with altered interactions between epithelium and connective tissue mediated by integrins localized in the basement membrane zone. We examined the expression of alpha2beta1, alpha3beta1, alpha4/alpha5/beta1, alpha6beta4 and their related extracellular matrix (ECM) ligands: laminin-1, laminin-5, and collagen type IV in untreated periodontitis sites of various categories. The expression and location of ECM proteins along the basement membrane were found to be similar between clinically healthy and periodontitis affected tissues. However, ECM proteins were more diffusely distributed in connective tissue (CT) of periodontitis tissues as streak-like/ fibrillar/granular stainings, particularly beneath the pocket epithelium (PE) and around the blood vessels. This may reflect an increase in inflammatory cell migration. The more widespread distribution of integrins alpha2beta1, alpha3beta1 in PE of periodontitis specimens may be related to disease activity and increased rate of keratinocyte proliferation and migration. Moreover, the weaker expression of alpha6beta4 in junctional epithelium (JE) of periodontitis affected tissues may be related to the epithelial detachment from the tooth surface. Clarification of expressions of integrins and their ligands in relation to known clinical disease susceptibility factors may provide information on the onset and progression mechanisms of periodontal disease destruction.

BAX protein is not expressed by basal cell carcinomas.

BAX and related proteins encoded by the BCL2 gene family are involved in the regulation of apoptosis. BAX is an apoptosis-promoting protein. The slow growth of basal cell carcinoma (BCC) has so far been explained by a high apoptotic activity. We investigated immunohistochemically 27 BCCs for expression of the apoptosis-promoting BAX protein. BCC did not express detectable amounts of BAX immunohistochemically. The results indicate that apoptosis in BCC does not involve BAX protein. We propose that the apoptotic pathway in BCC is regulated by either less common members of the BCL2 gene family or bypasses the regulation of the BCL2 gene family.

Can alterations in integrin and laminin-5 expression be used as markers of malignancy?

Development of squamous cell carcinomas (SCCs) involves alterations in the adhesive interactions in the epithelium and invasion through the basement membrane. Therefore, changes in the expression of receptors and ligands involved in cell-cell and cell-matrix adhesion may be essential for the transformation of a premalignant into a malignant lesion. The aim of this study was to examine if expression of specific cell adhesion molecules can be used as markers of malignant development. By immunohistochemistry, we examined the expression pattern of integrins alpha2beta1, alpha3beta1, alpha6beta4 and laminin-5 in biopsies from SCCs (n=18), premalignant lesions (leukoplakias, n=21) and non-premalignant tissue with chronic inflammation (n=11). In poorly differentiated SCCs, patchy loss of alpha3beta1, alpha6beta4 and laminin-5 expression was pronounced at the invasion front, whereas there was a tendency to increased expression of alpha2beta1. Analogous to the SCCs, biopsies from the leukoplakias and the non-premalignant inflammatory tissue showed alterations of the expression of alpha3beta1 and alpha6beta4 in the basal cell layers and of laminin-5. However, a characteristic finding in biopsies from leukoplakias was loss of alpha2beta1 and alpha3beta1 in the suprabasal cells. There was no unequivocal expression of the adhesion molecules distinguishing between inflammatory tissue, premalignant, and malignant lesions.

Differential expression of integrins and laminin-5 in normal oral epithelia.

beta 1 and beta 4 integrins are receptors on epithelial cells mediating cell-extracellular matrix adhesion. Furthermore, alpha 2 beta 1 and alpha 3 beta 1 contribute to cell-cell adhesion. Laminin-5 in epithelial basement membranes (BMs) is a ligand for alpha 6 beta 4 and alpha 3 beta 1. Expression of different integrins and laminin-5 was studied in oral epithelium to characterize regional variations in these adhesion molecules. Monoclonal antibodies directed against alpha 2-alpha 6 beta 1/alpha 6 beta 4 and laminin-5 were examined in cryopreserved biopsies of normal mucosa by immunohistochemistry. Laminin-5 was expressed as a line along the BMs. The junctional epithelium showed a unique phenotype: Laminin-5 was detected in the internal BM at the tooth surface and in the external BM, where excessive laminin-5 was seen in the stroma. alpha 6 beta 4 was expressed in all cells of the junctional epithelium. Integrins alpha 4 beta 1 and alpha 5 beta 1 were not detected in the epithelia, whereas alpha 2 beta 1 and alpha 3 beta 1 showed differential expression. Epithelia with well-developed rete pegs and connective tissue papillae showed polarized alpha 3 beta 1 expression along the BM in the rete pegs, in contrast to negative expression at the tips of the connective tissue papillae. A variation in the suprabasal distribution of alpha 2 beta 1 and alpha 3 beta 1 was observed between epithelia from different regions. alpha 2 beta 1 and alpha 3 beta 1 were detected in basal/parabasal cells in keratinized epithelia, whereas there was increased suprabasal expression in nonkeratinized mucosa. These results indicate inhomogeneity in the basal cell population of oral squamous epithelia and differential expression of integrins, which may reflect differences in the underlying stroma. Laminin-5 deposits in the stroma underneath the junctional epithelium may indicate subclinical gingival inflammation.