Long-term cognitive trajectories and heterogeneity in patients with schizophrenia and their unaffected siblings.

OBJECTIVE: This study aimed to assess the heterogeneity and stability of cognition in patients with a non-affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands. METHOD: Assessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group-based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance. RESULTS: Five stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients' alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003). CONCLUSIONS: The cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes.

Familial liability to psychosis is a risk factor for multimorbidity in people with psychotic disorders and their unaffected siblings.

BACKGROUND: Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity. METHODS: We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was defined as the presence of two or more complaints/diseases in the same individual. Generalized linear mixed model (GLMM) were used to investigate the effects of gender, age (adolescent, young, older) and familial liability (patients, siblings, controls) and their interactions on multimorbidity. RESULTS: Familial liability had a significant effect on multimorbidity of either complaints or diseases. Patients had a higher prevalence of multimorbidity of complaints compared to siblings (OR 2.20, 95% CI 1.79-2.69, P<0.001) and to controls (3.05, 2.35-3.96, P<0.001). In physical health multimorbidity, patients (OR 1.36, 95% CI 1.05-1.75, P=0.018), but not siblings, had significantly higher prevalence than controls. Similar finding were observed for multimorbidity of lifetime diseases, including psychiatric diseases. Significant results were observed for complaints and disease multimorbidity across gender and age groups. CONCLUSION: Multimorbidity is a common burden, significantly more prevalent in patients and their unaffected siblings. Familial liability to psychosis showed an independent effect on multimorbidity; gender and age are also important factors determining multimorbidity.

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

OBJECTIVE: Impaired insight is an important and prevalent symptom of psychosis. It remains unclear whether cognitive disturbances hamper improvements in insight. We investigated the neurocognitive, social cognitive, and clinical correlates of changes in insight. METHOD: One hundred and fifty-four patients with a psychotic disorder were assessed at baseline (T0 ) and after three years (T3 ) with the Birchwood Insight Scale, the Positive And Negative Syndrome Scale, measures of neurocognition and social cognition. Linear regression analyses were conducted to examine to what extend neurocognition, social cognition, clinical symptoms and phase of illness could uniquely predict insight change. Subsequently, changes in these factors were related to insight change. RESULTS: Better neurocognitive performance and fewer clinical symptoms at baseline explained insight improvements. The additional effect of clinical symptoms over and above the contribution of neurocognition was significant. Together, these factors explained 10% of the variance. Social cognition and phase of illness could not predict insight change. Changes in clinical symptoms, but not changes in neurocognitive performance were associated with insight change. CONCLUSION: Neurocognitive abilities may predict, in part, the development of insight in psychosis.

Cognitive subtypes in non-affected siblings of schizophrenia patients: characteristics and profile congruency with affected family members.

BACKGROUND: Although cognitive subtypes have been suggested in schizophrenia patients, similar analyses have not been carried out in their non-affected siblings. Subtype classification may provide more insight into genetically driven variation in cognitive function. We investigated cognitive subtypes in siblings. METHOD: Cluster analyses were performed in 654 non-affected siblings, on a cognitive battery that included tests of attention, intellectual function and episodic memory. Resulting subtypes in the siblings were analyzed for cognitive, demographic and clinical characteristics and compared with those of their probands. RESULTS: Three sibling subtypes of cognitive function were distinguished: 'normal', 'mixed' and 'impaired'. Normal profile siblings (n = 192) were unimpaired on cognitive tests, in contrast to their proband (n = 184). Mixed profile siblings (n = 228) and their probands (n = 222) had a more similar performance pattern. Impaired profile siblings had poorer functional outcomes (n = 234) and their profile was almost identical to that of their proband (n = 223). Probands with cognitively impaired siblings could be distinguished from other schizophrenia patients by their own cognitive performance. They also had poorer clinical characteristics, including achievement of symptomatic remission. CONCLUSIONS: Unaffected siblings of patients with schizophrenia are heterogeneous with respect to cognitive function. The poorer the cognitive profile of the sibling, the higher the level of correspondence with the proband. The sibling's cognitive subtype was predictive for disease course in the proband. Distinguishing cognitive subtypes of unaffected siblings may be of relevance for genetic studies.

Cannabis and cognitive performance in psychosis: a cross-sectional study in patients with non-affective psychotic illness and their unaffected siblings.

BACKGROUND: The relationship between cannabis use and cognitive functioning in patients with psychosis has yielded contradictory findings. In individuals at genetic high risk for psychosis, information is sparse. The aim of this study was to assess the association between recency and frequency of cannabis use and cognitive functioning in patients with psychosis and their unaffected siblings. METHOD: We conducted a cross-sectional study in 956 patients with non-affective psychosis, 953 unaffected siblings, and 554 control subjects. Participants completed a cognitive test battery including assessments of verbal learning, set shifting, sustained attention, processing speed, working memory, acquired knowledge, reasoning and problem solving and social cognition. Cannabis use was assessed by urinalysis and by the Composite International Diagnostic Interview. Using random-effect regression models the main effects of cannabis (recency and frequency) and the interaction with status (patient, sibling, control) on cognitive functioning were assessed. RESULTS: Current cannabis use was associated with poorer performance on immediate verbal learning, processing speed and working memory (Cohen's d -0.20 to -0.33, p<0.005). Lifetime cannabis use was associated with better performance on acquired knowledge, facial affect recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005). There was no significant interaction between cannabis and status on cognitive functioning. CONCLUSIONS: Lifetime cannabis-using individuals might constitute a subgroup with a higher cognitive potential. The residual effects of cannabis may impair short-term memory and processing speed.

Cognitive alterations in patients with non-affective psychotic disorder and their unaffected siblings and parents.

OBJECTIVE: The purpose of this study was to examine a range of cognitive measures as candidate phenotypic liability markers for psychosis in a uniquely large sample of patients with psychosis, their unaffected relatives and control subjects. METHOD: Patients with non-affective psychosis (n = 1093), their unaffected siblings (n = 1044), parents (n = 911), and controls (n = 587) completed a comprehensive cognitive test battery. Cognitive functioning was compared using tests of verbal learning and memory, attention/vigilance, working memory, processing speed, reasoning and problem solving, acquired knowledge, and social cognition. Age- and gender-adjusted z-scores were compared between groups using mixed-model analyses of covariance. Clinically relevant impairment (-1 and -2 SD from control mean) was compared between subject groups. RESULTS: Patients performed significantly worse than controls in all cognitive domains (z-range -0.26 to -1.34). Siblings and parents showed alterations for immediate verbal learning, processing speed, reasoning and problem solving, acquired knowledge, and working memory (z-range -0.22 to -0.98). Parents showed additional alterations for social cognition. Prevalence of clinically relevant impairment in relatives ranged from 50% (-1 SD criterion) to 10% (-2 SD criterion). CONCLUSION: Cognitive functioning is a candidate intermediate phenotype given significant small to large alterations in patients and intermediate alterations in first-degree relatives.