Association between cognitive phenotype in unaffected siblings and prospective 3- and 6-year clinical outcome in their proband affected by psychosis.

BACKGROUND: Cognitive alterations are a central and heterogeneous trait in psychotic disorders, driven by environmental, familial and illness-related factors. In this study, we aimed to prospectively investigate the impact of high familial risk for cognitive alterations, unconfounded by illness-related factors, on symptomatic outcomes in patients. METHODS: In total, 629 probands with non-affective psychosis and their sibling not affected by psychosis were assessed at baseline, 3- and 6-year follow-up. Familial cognitive risk was modeled by three cognitive subtypes ('normal', 'mixed' and 'impaired') in the unaffected siblings. Generalized linear mixed models assessed multi-cross-sectional associations between the sibling cognitive subtype and repeated measures of proband symptoms across all assessments. Between-group differences over time were assessed by adding an interaction effect of time and sibling cognitive subtype. RESULTS: Probands affected by psychosis with a sibling of the impaired cognitive subtype were less likely to be in symptomatic remission and showed more disorganization across all time points. When assessing differences over time, probands of siblings with the impaired cognitive subtype showed less remission and less improvement of disorganization after 3 and 6 years relative to the other subtypes. They also showed less reduction of positive, negative and excitement symptoms at 6-year follow-up compared to probands with a sibling of the normal cognitive subtype. CONCLUSIONS: Cross-sibling pathways from higher levels of familial cognitive vulnerability to worse long-term outcomes may be informative in identifying cognition-related environmental and genetic risks that impact psychotic illness heterogeneity over time.

Working memory in schizophrenia: a systematic study of specific modalities and processes.

Although many researchers agree that working memory (WM) impairments are a core symptom of schizophrenia, it remains unclear how the disturbances on specific WM components relate to one another. In this study, we presented a Delayed-Matching-To-Sample task to 24 schizophrenia patients and 24 healthy controls, matched on demographical variables. Verbal and visuospatial WM performance was investigated with pseudowords and Chinese characters as stimuli, respectively. Processing demands (maintenance and manipulation, measured with delay and mental rotation) were low or high. Reaction time and accuracy were recorded. All experimental factors had significant effects. In general, patients were slower and less accurate than controls. Patients were especially slower on verbal tasks but they were not less accurate. Accuracy differences did not increase when either maintenance or manipulation demands increased alone but they did when both maintenance and manipulation demands increased simultaneously. These findings indicate that performance impairment in patients was non-specific and that no specific deficit of any WM component was observed.

The validity of the DSM-IV diagnostic classification system of non-affective psychoses.

OBJECTIVE: The schizophrenia and other non-affective disorders categories listed in the DSM-IV, are currently under revision for the development of the fifth edition. The aim of the present study is to demonstrate the validity of these categories by investigating possible differences between diagnostic patient subgroups on various measures. METHODS: 1064 patients with a diagnosis of non-affective psychosis (schizophrenia N = 731 (paranoid type 82%), schizoaffective N = 63, schizophreniform N = 120, psychosis not otherwise specified/brief psychotic disorder N = 150) participated in this study. Dependent variables were demographic and clinical characteristics, severity of psychopathology, premorbid and current functioning, and indicators of quality of life. RESULTS: Within the diagnostic group of schizophrenia, no significant differences were observed between paranoid schizophrenia, disorganized, and undifferentiated schizophrenia. Patients with schizophrenia experienced more severe psychopathology and had poorer levels of current functioning compared to patients with psychosis not otherwise specified or brief psychotic disorder. Differences between schizophrenia and schizoaffective disorder were less clear. CONCLUSION: Our results do not support the validity of schizophrenia subtypes. Schizophrenia can be distinguished from brief psychotic disorder and psychotic disorder not otherwise specified. These findings may fuel the actual DSM-V discussion.

Effectiveness and cost-effectiveness of cognitive adaptation training as a nursing intervention in long-term residential patients with severe mental illness: study protocol for a randomized controlled trial.

BACKGROUND: Despite the well-known importance of cognitive deficits for everyday functioning in patients with severe mental illness (SMI), evidence-based interventions directed at these problems are especially scarce for SMI patients in long-term clinical facilities. Cognitive adaptation Training (CAT) is a compensatory approach that aims at creating new routines in patients' living environments through the use of environmental supports. Previous studies on CAT showed that CAT is effective in improving everyday functioning in outpatients with schizophrenia. The aim of this study is to evaluate the effect of CAT as a nursing intervention in SMI patients who reside in long-term clinical facilities. METHODS/DESIGN: This is a multicenter cluster randomized controlled trial comparing CAT (intervention group) as a nursing intervention to treatment as usual (control group). The primary goal is to evaluate the effectiveness of CAT on everyday functioning. Secondary outcomes are quality of life, empowerment and apathy. Further, an economic evaluation will be performed. The study has a duration of one year, with four follow-up assessments at 15, 18, 21 and 24 months for the intervention group. DISCUSSION: There is a need for evidence-based interventions that contribute to the improvement of the functional recovery of long-term residential patients. If our hypotheses are confirmed, it may be recommended to include CAT in the guidelines for SMI care and to implement the method in standardized care. TRIAL REGISTRATION: Nederlands Trial Register (identifier: NTR3308 ). Date registered: 12 February 2012.

Premorbid adjustment profiles in psychosis and the role of familial factors.

Disease heterogeneity in patients with psychotic disorder may be explained by distinct profiles of premorbid adjustment. The current study explored premorbid adjustment profiles in patients with psychotic disorders, associations with cognitive and clinical characteristics after disease onset, and the role of familial factors. A total of 666 patients with psychosis (predominantly schizophrenia), 673 siblings, 575 parents, and 585 controls were included in this study. Cluster analyses were performed on the patients' scores of the Premorbid Adjustment Scale (PAS), using information on domains (social, academic) and age epochs (childhood, early adolescence, late adolescence). Resulting profiles were compared with characteristics in patients and their unaffected relatives. Six clusters, labeled normal, social intermediate, academic decline, overall decline, overall intermediate, and overall impaired adjustment, were identified in patients. Patients in different clusters differed from each other on cognitive, clinical, and functional characteristics after disease onset. Heterogeneity in the patient population may be explained in part by the adjustment profile prior to disease onset. This is in line with theories that propose different etiologies in the development of psychosis. Patient profiles were expressed in unaffected siblings, suggesting a role for familial factors.

Improving functional outcomes for schizophrenia patients in the Netherlands using Cognitive Adaptation Training as a nursing intervention - A pilot study.

Cognitive Adaptation Training (CAT) improves functional outcomes in schizophrenia outpatients living in the United States. The effectiveness of CAT for patients living outside the US as well as for long-term hospitalized patients remains to be determined. In addition, it has not yet been studied whether CAT can be successful if patients receive the treatment from psychiatric nurses. This pilot study investigated the effectiveness and feasibility of CAT as a nursing intervention in the Netherlands. Thirty schizophrenia patients (long-term hospitalized patients: 63%) participated in this study. Sixteen patients received treatment as usual (TAU)+CAT, and fourteen patients received TAU. Patients in CAT participated in the treatment for eight months, consisting of weekly home-visits by a psychiatric nurse, supervised by a psychologist. After eight months, CAT interventions were integrated in the usual treatment. Outcome measures were the Multnomah Community Ability Scale (MCAS), the Social and Occupational Functioning Scale (SOFAS), and the Negative Symptom Assessment-Motivation subscale (NSA-M). For inpatients, work-related activities were also tracked for 16 months after baseline. Patients receiving TAU+CAT had better scores on the MCAS (trend), compared to TAU patients. Moreover, inpatients' work-related activities increased in TAU+CAT, relative to TAU inpatients, reaching significance after ten months. Improvements on the SOFAS and NSA-M were not significant. These results indicate that CAT as a nursing intervention may improve outcomes in patients with schizophrenia living in the Netherlands, including long-term hospitalized patients. However, since the current study was designed for exploratory purposes, larger randomized controlled studies are needed to confirm our results and to investigate the long-term effects of CAT as a nursing intervention systematically.

Cognitive adaptation training provided to chronically hospitalized patients with schizophrenia in the Netherlands: two case reports.

Cognitive adaptation training (CAT) improves functional outcome in outpatients with schizophrenia living in the United States of America. The efficacy of CAT has never been demonstrated for patients living in a residential facility. We describe how CAT was delivered to two chronically hospitalized patients with schizophrenia living in The Netherlands. CAT was delivered for 8 months, and consisted of weekly home visits by a psychiatric nurse. Both patients improved on measures of functional outcome used in the US studies. These results indicate that CAT may improve outcomes, even in patients that have been hospitalized for several years.

Genetic Risk and Outcome of Psychosis (GROUP), a multi-site longitudinal cohort study focused on gene-environment interaction: objectives, sample characteristics, recruitment and assessment methods.

OBJECTIVE: A longitudinal focus on gene-environment vulnerability and resilience in both patients, their unaffected family members and non-related controls offers the opportunity to elucidate etiological and pathogenetic factors influencing the onset and course of psychotic disorders. The current paper delineates the objectives, sample characteristics, recruitment and assessment procedures of the Genetic Risk and Outcome of Psychoses (GROUP) study. METHODS: A naturalistic longitudinal cohort study with assessments at baseline, after three and six years of follow-up. The study is conducted by a consortium of four university psychiatric centres, with their affiliated mental health care institutions in the Netherlands covering more than 7.5 million inhabitants. Extensive assessment of genetic factors, environmental factors, (endo)phenotypes, and outcome. RESULTS: At baseline, 1120 patients, 1057 siblings, 919 parents and 590 healthy controls were included. CONCLUSION: The GROUP study will contribute to insight in risk and protective factors in the aetiology of non-affective psychotic disorders, and in the variation in their course and outcome.

Insight in psychosis: relationship with neurocognition, social cognition and clinical symptoms depends on phase of illness.

Reduced insight has been reported in a majority of patients with a psychotic disorder. Most studies have focused on associations with neurocognition, neglecting relations with social cognition. Two hundred seventy patients with nonaffective psychosis participated in this study, which was part of the GROUP (Genetic Risk and OUtcome of Psychosis)-project. Linear regression analyses were performed to investigate the predictive value of composite measures of neurocognition, social cognition, and clinical symptoms. The moderating effect of phase of illness was also investigated. Insight was measured with a composite measure, based on the insight item on the Positive And Negative Syndrome Scale (PANSS) and the Birchwood Insight Scale (BIS). Insight on the BIS and the PANSS correlated significantly (r = .406). All independent variables correlated with the insight composite measure. The additional effect of social cognition and clinical symptoms were both significant. Phase of illness was a moderating variable: In patients with recent-onset psychosis (ROP), none of the independent variables explained variance. In patients with multiple episode or chronic psychosis, both social cognition and clinical symptoms had additional effects and explained insight, along with neurocognition, together explaining 20% of the variance. These findings indicate that multiple factors are associated with insight in psychosis. Specifically, associations of insight with social cognitive and clinical symptom measures were observed, over and above a contribution of neurocognition. This supports theories that imply a role for deficient emotion recognition and mentalizing in reduced insight. Further studies need to investigate insight in ROP into more detail.