Attilio Rapisarda

Impact of psychiatric comorbidity in individuals at Ultra High Risk of psychosis — Findings from the Longitudinal Youth at Risk Study (LYRIKS)

Recent studies have reported a high prevalence of psychiatric comorbidities in Ultra High Risk (UHR) for psychosis populations. This study examined the prevalence of comorbidity and its impact on symptoms, functioning, cognition and transition to psychosis in the Longitudinal Youth at Risk Study (LYRIKS) sample. The Comprehensive Assessment of At-Risk Mental State (CAARMS) was used to identify UHR individuals and 163 participants were included in the study. Comorbid disorders were identified using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Participants were evaluated on the CAARMS, Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Beck Anxiety Inventory, Global Assessment of Functioning and Brief Assessment of Cognition in Schizophrenia. Clinical, functioning and cognitive characteristics by lifetime and current comorbidity groups were compared using multivariate tests. Independent predictors of comorbidity were identified through logistic regression. Chi-squared tests were used to compare comorbidity rates between those who had developed psychosis at one year and those who had not. We found that 131 UHR participants (80.4%) had a lifetime comorbidity while 82 (50.3%) had a current comorbidity with depressive disorders being the most common. UHR individuals with comorbidity had more severe symptoms, higher distress and lower functioning with no differences in general cognition. Lower functioning was associated with current comorbidity. Eleven participants (6.7%) had developed psychosis after one year and there were no differences in the comorbidity rates between those who developed psychosis and those who did not. Psychiatric comorbidities in the UHR group are associated with adverse clinical outcomes and warrant closer attention.

The Longitudinal Youth at Risk Study (LYRIKS) — An Asian UHR perspective

Numerous studies have been published on the psychosis prodrome and have explored a wide array of its many aspects. However, the set of risk factors identified by these various efforts is not homogenous across studies. This could be due to unique population factors or relatively small sample sizes. Only few studies were conducted on Asian populations, whose socio-cultural characteristics differ - in some cases remarkably - from those in western populations. Singapore is a highly dense city-state in South-east Asia, with low rates of substance abuse. The Longitudinal Youth at Risk Study (LYRIKS) commenced in Singapore in 2008, designed to comprehensively assess a group of ultra high risk (UHR) individuals and identify clinical, social, neuropsychological and biological risk factors unique to the local population. 173 UHR individuals were recruited from this single-site study over 4 years. Here, we detail aspects of the study methodology and report on the baseline social and clinical characteristics of the sample population. 78% of the UHR sample suffered from a psychiatric disorder, with Major Depressive Disorder present in more than half of the sample. The mean Global Assessment of Functioning (GAF) score was 57.4, which indicated a moderate level of impairment. Although the recruited sample did not differ significantly by social and clinical characteristics when compared to previously published reports, the conversion rate to psychosis was 3.5% (n=6) at 6 months. Follow-up measures are currently underway to assess longitudinal incidence of psychosis and impact of risk factors on cognition, functioning and remission.

Formulation of the age-education index: measuring age and education effects in neuropsychological performance

The complex interplay of education, age, and cognitive performance on various neuropsychological tests is examined in the current study. New education indices were formulated and further investigated to reveal how age and education variances work together to account for performance on neuropsychological tests. Participants were 830 English-speaking ethnic Chinese. Neuropsychological measures such as Verbal Memory, Digit Sequencing, Token Motor Task, Semantic Fluency, Symbol Coding, Tower of London, Judgment of Line Orientation, and Matrix Reasoning of the Wechsler Adult Intelligence Scale were administered. Education was measured by total years of education and adjusted years of education, as well as ratios of both measures with age. Age and education were associated with neuropsychological performance. Adjusted years of education was associated with fluency and higher cognitive processes, while the ratio between adjusted years of education and age was associated with tasks implicating working memory. Changes in education modalities implicated tasks requiring language abilities. Education and age represent key neurodevelopmental milestones. In light of our findings, special consideration should to be given when neuropsychological assessments are carried out in cross-cultural contexts and in societies where educational systems and pedagogy tend to be complex.

Applicability of the MATRICS Consensus Cognitive Battery in Singapore

The MATRICS Consensus Cognitive Battery (MCCB) was developed to provide a reliable, valid, and standard battery for clinical trials on cognitive enhancers in schizophrenia. In this study we tested the applicability of the MCCB to Singapore’s English speakers. Healthy ethnic Chinese, Malay, and Indian English speakers (N = 171) of both genders were recruited within three age groups and three levels of education to match as closely as possible the US norming sample, and were administered the MCCB. Descriptive data, T scores, age, gender, education, and ethnicity effects on performance were explored and compared with the US norming study. Age, education, and ethnicity affected the battery’s composite scores, with young and highly educated participants generally outperforming the old, less-educated ones. Male participants outperformed their female counterparts in two out of seven cognitive domains. Although generally lower when compared to the US norming sample, Singaporean scores reflected the same relationship with age, education, and gender, with the exception of a substantially worse performance in the social cognition domain. Differences among the ethnic groups in Singapore—and the poorer performance measured in these groups with respect to the US sample—call for the necessity of an extended norming study in Singapore.

Refining the latent structure of neuropsychological performance in schizophrenia.

BACKGROUND Elucidating the cognitive architecture of schizophrenia promises to advance understanding of the clinical and biological substrates of the illness. Traditional cross-sectional neuropsychological approaches differentiate impaired from normal cognitive abilities but are limited in their ability to determine latent substructure. The current study examined the latent architecture of abnormal cognition in schizophrenia via a systematic approach. METHOD Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were carried out on a large neuropsychological dataset including the Brief Assessment of Cognition in Schizophrenia, Continuous Performance Test, Wisconsin Card Sorting Test, Benton Judgment of Line Orientation Test, and Wechsler Abbreviated Scale of Intelligence matrix reasoning derived from 1012 English-speaking ethnic Chinese healthy controls and 707 schizophrenia cases recruited from in- and out-patient clinics. RESULTS An initial six-factor model fit cognitive data in healthy and schizophrenia subjects. Further modeling, which accounted for methodological variance between tests, resulted in a three-factor model of executive functioning, vigilance/speed of processing and memory that appeared to best discriminate schizophrenia cases from controls. Factor analytic-derived g estimands and conventionally calculated g showed similar case-control discrimination. However, agreement analysis suggested systematic differences between both g indices. CONCLUSIONS Factor structures derived in the current study were broadly similar to those reported previously. However, factor structures between schizophrenia subjects and healthy controls were different. Roles of factor analytic-derived g estimands and conventional composite score g were further discussed. Cognitive structures underlying cognitive deficits in schizophrenia may prove useful for interrogating biological substrates and enriching effect sizes for subsequent work.

The relationship between negative symptom subdomains and cognition.

BACKGROUND Negative symptoms and cognitive deficits in schizophrenia are partially overlapping. However, the nature of the relationship between negative symptoms and cognition remains equivocal. Recent reviews have demonstrated the presence of two negative symptom subdomains, diminished emotional expression (DEE) and avolition. In view of this, we sought to clarify the relationship between negative symptoms and cognitive domains. METHOD A total of 687 participants with schizophrenia were assessed on measures of psychopathology and cognition. Three cognitive factors, namely executive function, fluency/memory and speed/vigilance were computed from the cognitive tests. Confirmatory factor analysis was utilized to examine if a one-factor or two-factor negative model was applicable to our sample. Subsequently, the relationships between negative symptoms and cognition were examined using structural equation modeling. RESULTS Results demonstrated that the two-factor model fitted the data well. While negative symptoms were mildly to moderately associated with cognition, we found that DEE had unique associations with cognition compared to social avolition, contributing to the validity of the constructs and suggesting the possibility of common underlying substrates in negative symptoms and cognition. CONCLUSIONS Our study highlighted the need to classify DEE and social avolition separately as both are necessary in refining the complex relationship between negative symptoms and cognition as well as potentially guiding treatment and management of schizophrenia.

Brief Assessment of Cognition in Schizophrenia: Normative Data in an English-Speaking Ethnic Chinese Sample

There is a dearth of non-Western normative data for neuropsychological batteries designed to measure cognitive deficits in schizophrenia. Here, we provide normative data for English-speaking ethnic Chinese on the widely used Brief Assessment of Cognition in Schizophrenia acquired from 595 healthy community participants between ages 14 and 55. Means and standard deviations of subtests and composite scores were stratified by age group and sex. We also explored linear regression approaches to generate continuous norms adjusted for age, sex, and education. Notable differences in subtest performances were found against a Western comparison sample. Normative data established in the current sample are essential for clinical and research purposes as it serves as a reference source of cognition for ethnic Chinese.

Disrupted latent inhibition in individuals at ultra high-risk for developing psychosis

The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subjects tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.

The Impact of Medication Anticholinergic Burden on Cognitive Performance in People With Schizophrenia

Background Cognitive deficits are prevalent in people with schizophrenia and associated with functional impairments. In addition to antipsychotics, pharmacotherapy in schizophrenia often includes other psychotropics, and some of these agents possess anticholinergic properties, which may impair cognition. The objective of this study was to explore the association between medication anticholinergic burden and cognition in schizophrenia. Methods Seven hundred five individuals with schizophrenia completed a neuropsychological battery comprising Judgment of Line Orientation Test, Wechsler Abbreviated Scale of Intelligence Matrix Reasoning, Continuous Performance Test–Identical Pairs Version, and the Brief Assessment of Cognition in Schizophrenia. Cognitive g and 3 cognitive factor scores that include executive function, memory/fluency, and speed of processing/vigilance, which were derived from a previously published analysis, were entered as cognitive variables. Anticholinergic burden was computed using 2 anticholinergic scales: Anticholinergic Burden Scale and Anticholinergic Drug Scale. Duration and severity of illness, antipsychotic dose, smoking status, age, and sex were included as covariates. Results Anticholinergic burden was associated with poorer cognitive performance in cognitive g, all 3 cognitive domains and most cognitive tasks in multivariate analyses. The associations were statistically significant, but the effect sizes were small (for Anticholinergic Burden Scale, Cohen f2 = 0.008; for Anticholinergic Drug Scale, Cohen f2 = 0.017). Conclusions Although our results showed a statistically significant association between medications with anticholinergic properties and cognition in people with schizophrenia, the impact is of doubtful or minimal clinical significance.

Impact of distress related to attenuated psychotic symptoms in individuals at ultra high risk of psychosis: Findings from the Longitudinal Youth at Risk Study

Recent studies have highlighted that attenuated psychotic symptoms (APS) are an important source of distress in ultra high risk (UHR) individuals and that this distress is related to transition to psychosis (TTP). This study examined distress associated with APS in UHR individuals and investigated its association with TTP.