Cognitive impairment as a risk factor for psychosis

2005

CONTENTS ABBREVIATIONS LIST OF ORIGINAL PUBLICATIONS 1 INTRODUCTION 2 REVIEW OF THE LITERATURE 2.1 SCHIZOPHRENIC DISORDERS 2.1.1 Schizophrenia 2.1.2 Schizophreniform disorder 2.1.3 Schizoaffective disorder 2.1.4 Schizotypal and schizoid personality disorder 2.2 COGNITIVE IMPAIRMENT AND SYMPTOMS IN SCHIZOPHRENIA 2.3 COGNITIVE DYSFUNCTIONS IN SCHIZOPHRENIA 2.3.1 Attention 2.3.2 Declarative memory 2.3.3 Working memory 2.3.4 Executive function 2.4 SPECTRUM DISORDERS AND COGNITIVE IMPAIRMENTS 2.5 SCHIZOPHRENIA AND BIPOLAR DISORDER-SIMILAR OR DIFFERENT COGNITIVE IMPAIRMENT? 2.6 PSYCHOPHARMACOLOGICAL TREATMENT AND COGNITION IN SCHIZOPHRENIA 2.7 ETIOLOGY OF SCHIZOPHRENIA 2.7.1 The neurodevelopmental theory of schizophrenia 2.7.2 Environmental factors 2.7.3 Genetic factors 2.7.4 Epigenetic effects 2.8 STRUCTURAL AND FUNCTIONAL BRAIN ABNORMALITIES IN SCHIZOPHRENIA 2.9 COGNITIVE DYSFUNCTIONS IN RELATIVES OF PATIENTS WITH SCHIZOPHRENIA 2.10 STRUCTURAL AND FUNCTIONAL BRAIN ABNORMALITIES IN RELATIVES OF SCHIZOPHRENIA PATIENTS 2.11 ENDOPHENOTYPES IN THE GENE SEARCH 2.11.1 The concept of endophenotype 2.11.2 Neuropsychological endophenotypes 2.11.3 Quantitative trait loci and schizophrenia 8 3 AIMS OF THE STUDY 4 SUBJECTS AND METHODS 4.1 THE STUDY PROJECT 4.2 SUBJECTS 4.2.1 Subjects in the Study I 4.2.2 Subjects in the Study II 4.2.3 Subjects in the Study III 4.2.4 Subjects in the Study IV 4.2.5 Subjects in the Study V 4.3 THE NEUROPSYCHOLOGICAL TEST PROCEDURES 4.4 STATISTICAL ANALYSES 4.4.1 Statistical analyses in the Study I 4.4.2 Statistical analyses in the Study II 4.4.3 Statistical analyses in the Study III 4.4.4 Statistical analyses in the Study IV 4.4.5 Statistical analyses in the Study V 4.4.5.1 Cluster analysis 4.4.5.2 Visualization of the clusters 4.4.5.3 Difference testing between the clusters 5 RESULTS 5.1 HERITABILITY OF COGNITIVE FUNCTIONS AND THE NUMBER OF THEIR RESPECTIVE LOCI (STUDY I) 5.1.1 Heritability 5.1.2 Number of QTLs 5.2 EFFECT OF FAMILIAL LOADING ON THE COGNITIVE FUNCTIONS AMONG RELATIVES OF SCHIZOPHRENIA PATIENTS (STUDY II) 5.3 EFFECT OF AGE OF ONSET ON COGNITIVE FUNCTIONS IN SCHIZOPHRENIA (STUDY III) 5.3.1 Effect of age of onset 5.3.2 Fixed effect contributions 5.4 GENOMEWIDE QTL-ANALYSIS OF COGNITIVE TRAIT COMPONENTS IN SCHIZOPHRENIA (STUDY IV) 5.4.1 Genomewide search 5.4.2 Genomewide p-values 9 5.5 COGNITIVE CLUSTERS AMONG FAMILIES REPRESENTING FAMILIAL SCHIZOPHRENIA (STUDY V) 5.5.1 The cluster solution 5.5.2 Demographic and clinical characteristics 5.5.3 Neuropsychological variables 5.5.4 Effect of education 6 DISCUSSION 6.1 ARE COGNITIVE DYSFUNCTIONS HERITABLE IN SCHIZOPHRENIA? 6.2 COGNITIVE FUNCTIONING IN THE HEALTHY RELATIVES OF

Psychiatry Research, 1994

This study was designed to identify the types of neuropsychological deficits that are unique to familial and nonfamilial forms of schizophrenia. Seventy-two patients who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder, mainly schizophrenic, were divided into two groups on the basis of the presence or absence of a family history of psychosis. The two groups were then compared for differences on six neuropsychological parameters as well as for differences in psychotic symptoms. Multivariate analyses indicated that schizophrenic patients with a family history of psychosis showed significantly higher levels of overall neuropsychological deficit and significantly greater deficits on tests of motor-control and abstraction and problem-solving. Factor analyses indicate that schizophrenic patients with a family history of psychosis show a pattern of specific neuropsychological deficits, while schizophrenic patients without a family history show a pattern of more consistent cognitive deficits. The results of this study indicate that recent-onset schizophrenic patients with and without a family history of psychosis show distinctly different patterns of neuropsychological dysfunction. These data suggest that abnormalities in the dorsolateral prefrontal cortex and nonprimary motor areas may be associated with an increased familial risk for psychotic disorder.

Comprehensive Psychiatry, 2006

Objective: Our purpose in undertaking the present study was to explore the existence of specific areas of cognitive deficits within the context of generalized poor performance in a group of Greek patients with schizophrenia. We also sought to identify any patients who might be cognitively normal. Method: Participants were 70 patients with schizophrenia and 42 healthy control subjects. The 2 groups were matched on age and male-female ratio but differed in their level of education. A battery of neuropsychological tests was selected to assess executive functions/abstraction, fluency, verbal and spatial working memory, verbal and nonverbal memory, attention, visuospatial ability, and psychomotor speed. Results: Patients with schizophrenia performed more poorly than healthy control subjects, when we controlled for differences in level of education, on executive functions, working memory, verbal memory, nonverbal memory, fluency, visuospatial ability, and attention. In contrast, no significant differences were found between the 2 groups on psychomotor speed. Patients showed a more pronounced deficit on executive functions, verbal and visual memory, and visuospatial ability. Overall, 13% to 62% of the patients with schizophrenia scored within 1 SD of the mean z scores of healthy control group depending on the cognitive domains examined. In the entire sample of patients with schizophrenia, however, no individual scored within 1 SD of the mean z scores of the control group in all cognitive domains. Conclusions: We found a generalized deficit in cognitive functioning in a group of patients with schizophrenia. We failed to find any individual patients who were healthy across all cognitive areas. The current neuropsychological profile, indicating widespread impairment, is comparable to that reported in the international literature and thus appears to be characteristic of schizophrenia. Our findings of increased difficulties with executive functions, verbal and visual memory, and visuospatial ability support previous suggestions of generalized brain dysfunction in the pathophysiology of schizophrenia. D

Molecular Psychiatry

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range =-0.45 to-0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES =-0.14 to-0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range =-0.88 to-0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range =-0.13 to-0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range =-0.21 to-0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Psychiatry Research, 2013

Cognitive deficits have been found to be more prevalent in psychotic than in other disorders. Longitudinal research has shown that these deficits were generally already existent before onset of illness and are therefore not necessarily attributable to neurodegenerative processes. This study investigated whether both low IQ and markers of premorbid cognitive dysfunction independently contribute to an increased risk for psychoses. In a cross-sectional study about 50,000 young Swiss males completed a survey of intellectual problems in childhood/adolescence and other vulnerability factors during military call-up in 2005/2006. Subsequently, military IQ assessments were carried out on the entire sample. Diagnostic assessments were conducted according to International Classification of Diseases-10th edition (ICD-10). Low, especially performance, IQ was highly associated with an increased risk for psychotic disorders after adjusting for preexisting cognitive deficits and covariates, while in other disorders this association was less marked. Furthermore, preexisting intellectual problems emerged as important risk factors for psychoses. Our results confirm the importance of low IQ as characteristic of psychoses. Although premorbid intellectual deficits are common in people who go on to develop psychosis, neurodegenerative disease processes may also precipitate further declines in fluid cognitive functions. Assessment of cognitive functioning should be taken into account in early detection of psychoses. M. Müller). Please cite this article as: Müller, M., et al., Precursors of cognitive impairments in psychotic disorders: A population-based study. Psychiatry Research (2013), http://dx.