Association of cognitive performance with clinical staging in schizophrenia spectrum disorders: a prospective 6-year follow-up study.

BACKGROUND: Clinical staging has been developed to capture the large heterogeneity in schizophrenia spectrum disorders. Including cognitive performance in the staging model may improve its clinical validity. Moreover, cognitive functioning could predict transition across stages. However, current evidence of the association between cognition and clinical staging is inconsistent. Therefore, we aim to assess whether cognitive parameters are associated with clinical stages in a large sample of patients with schizophrenia spectrum disorders and to identify cognitive markers at baseline that are associated with stage-transition at three and six-year follow-up. METHODS: We applied the staging model of Fusar-Poli et al. (2017) in 927 patients with non-affective psychotic disorders, assessed at baseline, and after three and six-year follow-up. Cognitive performance was assessed with a standard test battery. Generalized linear mixed models were used to analyze associations of cognitive performance with staging and stage-transition at follow-up. RESULTS: Findings showed that higher stages of illness were significantly associated with lower processing speed (F = 3.688, p = 0.025) and deficits in working memory (F = 6.365, p = 0.002) across assessments. No associations between cognitive parameters at baseline and stage-transition at three- and six-year follow-up were found. CONCLUSION: We conclude that processing speed and working memory were modestly associated with higher stages of illness in schizophrenia spectrum disorders, thereby slightly improving its clinical validity. However, associations were small and we found no evidence for predictive validity.

[The importance of inter-rater reliability in psychopharmacological trials]. / Het belang van interbeoordelaars­betrouwbaarheid in psychofarmacologisch onderzoek.

BACKGROUND: There are concerns about the declining efficacy of antidepressants and antipsychotics in clinical trials. A potential cause may be found in poor training practices to achieve sufficient inter-rater reliability (IRR). However, it is unknown whether IRR and training procedures are currently reported. AIM: To determine the proportion of publications concerning double-blind randomized controlled trials (RCTs) investigating antipsychotics or antidepressants that report IRR and training procedures. METHOD: We extracted all double-blind RCTs from five large meta-analyses concerning antidepressants and antipsychotics. Further, we conducted a Medline-search for double-blind RCTs investigating antidepressants from January 2016 - January 2020, and antipsychotics from January 2000 - January 2019. RESULTS: In 179 double-blind RCTs with antidepressants, only 4.5% reported an IRR coefficient whereas 27.9% reported on training procedures. Further, in 207 double-blind RCTs with antipsychotics, 11.2% reported an IRR coefficient and 34.8% reported training procedures. CONCLUSION: There is a substantial lack of reporting IRR and training procedures in RCTs with antidepressants and antipsychotics. Considering the implications of insufficient IRR, it is necessary to conduct and report training procedures and IRR. Reporting IRR and training procedures should be made mandatory by editorial boards of scientific journals.

Psychometric properties of the DSM-5 Clinician-Rated Dimensions of Psychosis Symptom Severity.

OBJECTIVE: The Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) was presented in the DSM-5 as a new scale to assess the dimensional aspects of psychosis in daily clinical practice. However, agreement in CRDPSS-ratings among raters in clinical practice remains unknown. We examined the inter-rater reliability (IRR) and convergent validity of the CRDPSS. METHOD: Consecutively recruited outpatients with recent onset schizophrenia spectrum disorders were included between January 2015 and July 2018. We collected multiple CRDPSS measurements of 335 participants, of whom 179 PANSS measurements were available. IRR was determined by comparing the CRDPSS-ratings of psychiatrists with a vis-à-vis contact and CRDPSS observations based on a detailed clinical presentation. IRR was expressed in Krippendorff's alpha and we estimated convergent validity by studying associations with PANSS factors by Spearman's rank correlation coefficient. RESULTS: Inter-rater reliability scores measured in Krippendorff's alpha were low (0.35-0.64) for all items of the CRDPSS, except the item delusions (0.74). A three-factor model was found: 'deficit/motor symptoms', 'positive symptoms' and 'mood symptoms'. Positive associations between CRDPSS factors with PANSS factors were found. CONCLUSION: This study demonstrated that the IRR of the CRDPSS between raters in clinical practice was insufficient. We did find some supporting evidence for convergent validity of the CRDPSS, but these results should be interpreted carefully due to low IRR. Consequently, general implementation in clinical practice should be done with caution and we recommend assessors to be trained.

Satisfaction of psychotic patients with care and its value to predict outcomes.

BACKGROUND: A key indicator of quality of treatment from the patient's perspective is expressed by satisfaction with care. Our aim was to (i) explore satisfaction and its relation to clinical outcome measures; and (ii) explore the predictive value of satisfaction for the course of outcomes over three years. METHODS: Data of 654 patients with a non-affective psychosis included in a naturalistic longitudinal cohort study were analyzed. We included 506 males and 148 females with a mean age of 30.47 (SD 7.24) from The Netherlands. Satisfaction was measured with the self-rating Client Satisfaction Questionnaire-8. A wide range of interviewer-rated (e.g., Positive and Negative Symptom Scale) and self-rated (e.g., World Health Organization Quality of Life); outcomes of low, intermediate and high satisfied patients were compared using ANOVA, Chi2 or Kruskal-Wallis tests. The predictive value of satisfaction level on clinical outcomes after three years was tested using regression models. RESULTS: Satisfaction levels were low (19.4%), intermediate (48.9%) or high (31.7%). High satisfied patients showed significantly better interviewer-rated outcomes, e.g., less severe psychotic symptoms, and self-rated outcomes, e.g., better quality of life, compared to patients with intermediate or low satisfaction. Higher levels of satisfaction with care at baseline predicted a reduction of positive symptoms three years later (B=-.09, P-value=.013). CONCLUSIONS: Satisfaction of patients with psychosis is a valuable monitoring measure since high satisfied patients show more favorable outcomes ranging from psychopathological symptoms to quality of life. Further research into explanations of lower levels of satisfaction is commendable in order to improve outcomes.

Antipsychotic medication and long-term mortality risk in patients with schizophrenia; a systematic review and meta-analysis.

Patients with schizophrenia have a higher mortality risk than patients suffering from any other psychiatric disorder. Previous research is inconclusive regarding the association of antipsychotic treatment with long-term mortality risk. To this aim, we systematically reviewed the literature and performed a meta-analysis on the relationship between long-term mortality and exposure to antipsychotic medication in patients with schizophrenia. The objectives were to (i) determine long-term mortality rates in patients with schizophrenia using any antipsychotic medication; (ii) compare these with mortality rates of patients using no antipsychotics; (iii) explore the relationship between cumulative exposure and mortality; and (iv) assess causes of death. We systematically searched the EMBASE, MEDLINE and PsycINFO databases for studies that reported on mortality and antipsychotic medication and that included adults with schizophrenia using a follow-up design of more than 1 year. A total of 20 studies fulfilled our inclusion criteria. These studies reported 23,353 deaths during 821,347 patient years in 133,929 unique patients. Mortality rates varied widely per study. Meta-analysis on a subgroup of four studies showed a consistent trend of an increased long-term mortality risk in schizophrenia patients who did not use antipsychotic medication during follow-up. We found a pooled risk ratio of 0.57 (LL:0.46 UL:0.76 p value <0.001) favouring any exposure to antipsychotics. Statiscal heterogeneity was found to be high (Q = 39.31, I 2 = 92.37%, p value < 0.001). Reasons for the increased risk of death for patients with schizophrenia without antipsychotic medication require further research. Prospective validation studies, uniform measures of antipsychotic exposure and classified causes of death are commendable.

Increased saccadic rate during smooth pursuit eye movements in patients at Ultra High Risk for developing a psychosis.

Abnormalities in eye tracking are consistently observed in schizophrenia patients and their relatives and have been proposed as an endophenotype of the disease. The aim of this study was to investigate the performance of patients at Ultra High Risk (UHR) for developing psychosis on a task of smooth pursuit eye movement (SPEM). Forty-six UHR patients and twenty-eight age and education matched controls were assessed with a task of SPEM and psychiatric questionnaires. Our results showed that both the corrective and non-corrective saccadic rates during pursuit were higher in the UHR group. There were however no differences in smooth pursuit gain between the two groups. The saccadic rate was related to positive UHR symptoms. Our findings indicate that abnormalities in SPEM are already present in UHR patients, prior to a first psychotic episode. These abnormalities occur only in the saccadic system.