Jan Richard

A cognitive neuroscience based computerized battery for efficient measurement of individual differences: Standardization and initial construct validation

There is increased need for efficient computerized methods to collect reliable data on a range of cognitive domains that can be linked to specific brain systems. Such need arises in functional neuroimaging studies, where individual differences in cognitive performance are variables of interest or serve as confounds. In genetic studies of complex behavior, which require particularly large samples, such trait measures can serve as endophenotypes. Traditional neuropsychological tests, based on clinical pathological correlations, are protracted, require extensive training in administration and scoring, and leave lengthy paper trails (double-entry for analysis). We present a computerized battery that takes an average of 1h and provides measures of accuracy and speed on 9 neurocognitive domains. They are cognitive neuroscience-based in that they have been linked experimentally to specific brain systems with functional neuroimaging studies. We describe the process of translating tasks used in functional neuroimaging to tests for assessing individual differences. Data are presented on each test with samples ranging from 139 (81 female) to 536 (311 female) of carefully screened healthy individuals ranging in age from 18 to 84. Item consistency was established with acceptable to high Cronbach alpha coefficients. Inter-item correlations were moderate to high within domain and low to nil across domains, indicating construct validity. Initial criterion validity was demonstrated by sensitivity to sex differences and the effects of age, education and parental education. These results encourage the use of this battery in studies needing an efficient assessment of major neurocognitive domains such as multi-site genetic studies and clinical trials.

Development of abbreviated nine-item forms of the Raven's standard progressive matrices test.

The Raven’s Standard Progressive Matrices (RSPM) is a 60-item test for measuring abstract reasoning, considered a nonverbal estimate of fluid intelligence, and often included in clinical assessment batteries and research on patients with cognitive deficits. The goal was to develop and apply a predictive model approach to reduce the number of items necessary to yield a score equivalent to that derived from the full scale. The approach is based on a Poisson predictive model. A parsimonious subset of items that accurately predicts the total score was sought, as was a second nonoverlapping alternate form for repeated administrations. A split sample was used for model fitting and validation, with cross-validation to verify results. Using nine RSPM items as predictors, correlations of .9836 and .9782 were achieved for the reduced forms and .9063 and .8978 for the validation data. Thus, a 9-item subset of RSPM predicts the total score for the 60-item scale with good accuracy. A comparison of psychometric properties between 9-item forms, a published 30-item form, and the 60-item set is presented. The two 9-item forms provide a 75% administration time savings compared with the 30-item form, while achieving similar item- and test-level characteristics and equal correlations to 60-item based scores.

Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS): Evidence for Impairment and Heritability of Neurocognitive Functioning in Families of Schizophrenia Patients

OBJECTIVE Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. METHOD Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. RESULTS The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. CONCLUSION Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies.

Facial emotion perception differs in young persons at genetic and clinical high-risk for psychosis

A large body of literature has documented facial emotion perception impairments in schizophrenia. More recently, emotion perception has been investigated in persons at genetic and clinical high-risk for psychosis. This study compared emotion perception abilities in groups of young persons with schizophrenia, clinical high-risk, genetic risk and healthy controls. Groups, ages 13-25, included 24 persons at clinical high-risk, 52 first-degree relatives at genetic risk, 91 persons with schizophrenia and 90 low risk persons who completed computerized testing of emotion recognition and differentiation. Groups differed by overall emotion recognition abilities and recognition of happy, sad, anger and fear expressions. Pairwise comparisons revealed comparable impairments in recognition of happy, angry, and fearful expressions for persons at clinical high-risk and schizophrenia, while genetic risk participants were less impaired, showing reduced recognition of fearful expressions. Groups also differed for differentiation of happy and sad expressions, but differences were mainly between schizophrenia and control groups. Emotion perception impairments are observable in young persons at-risk for psychosis. Preliminary results with clinical high-risk participants, when considered along findings in genetic risk relatives, suggest social cognition abilities to reflect pathophysiological processes involved in risk of schizophrenia.

Adjunctive cognitive remediation for schizophrenia using yoga: an open, non-randomized trial

Background: Yoga therapy (YT) improves cognitive function in healthy individuals, but its impact on cognitive function among persons with schizophrenia (SZ) has not been investigated. Objective: To evaluate the adjunctive YT for cognitive domains impaired in SZ. Methods: Patients with SZ received YT or treatment as usual (TAU; n = 65, n = 23, respectively). Accuracy and speed for seven cognitive domains were assessed using a computerised neurocognitive battery (CNB), thus minimising observer bias. Separately, YT was evaluated among patients with bipolar I disorder (n = 40), major depressive disorder (n = 37) and cardiology outpatients (n = 68). All patients also received routine pharmacotherapy. Patients were not randomised to YT or TAU. Results: In comparison with the SZ/TAU group, the SZ/YT group showed significantly greater improvement with regard to measures of attention following corrections for multiple comparisons; the changes were more prominent among the men. In the other diagnostic groups, differing patterns of improvements were noted with small-to-medium effect sizes. Conclusions: Our initial analyses suggest nominally significant improvement in cognitive function in SZ with adjunctive therapies such as YT. The magnitude of the change varies by cognitive domain and may also vary by diagnostic group.

Neurocognitive Performance Stability in a Multiplex Multigenerational Study of Schizophrenia

Certain cognitive measures are heritable and differentiate individuals at risk for schizophrenia from unaffected family members and healthy comparison subjects. These deficits in neurocognitive performance in patients with schizophrenia appear stable in the short-term. However, the duration of most, but not all, longitudinal studies is modest and the majority have relied on traditional average performance measures to examine stability. Using a computerized neurocognitive battery (CNB), we assessed mean performance (accuracy and speed) and intra-individual variability (IIV) in a longitudinal study aimed to examine neurocognitive stability in European-American multiplex families with schizophrenia. Thirty-four patients with schizophrenia, 65 unaffected relatives, and 45 healthy comparison subjects completed the same computerized neurocognitive assessment over approximately 5 years. Measures of mean performance showed that patients had stable accuracy performance but were slower in many neurocognitive domains over time as compared with unaffected family members and healthy subjects. Furthermore, patients and family members showed dissociable patterns of change in IIV for speed across cognitive domains: compared with controls, patients showed higher across-task IIV in performance compared with family members, who showed lower across-task IIV. Patients showed an increase in IIV over time, whereas family members showed a decrease. These findings suggest that measures of mean performance and IIV of speed during a CNB may provide useful information about the genetic susceptibility in schizophrenia.

Facial emotion recognition in adolescents with psychotic-like experiences: a school-based sample from the general population.

BACKGROUND Psychotic symptoms, also termed psychotic-like experiences (PLEs) in the absence of psychotic disorder, are common in adolescents and are associated with increased risk of schizophrenia-spectrum illness in adulthood. At the same time, schizophrenia is associated with deficits in social cognition, with deficits particularly documented in facial emotion recognition (FER). However, little is known about the relationship between PLEs and FER abilities, with only one previous prospective study examining the association between these abilities in childhood and reported PLEs in adolescence. The current study was a cross-sectional investigation of the association between PLEs and FER in a sample of Irish adolescents. METHOD The Adolescent Psychotic-Like Symptom Screener (APSS), a self-report measure of PLEs, and the Penn Emotion Recognition-40 Test (Penn ER-40), a measure of facial emotion recognition, were completed by 793 children aged 10-13 years. RESULTS Children who reported PLEs performed significantly more poorly on FER (β=-0.03, p=0.035). Recognition of sad faces was the major driver of effects, with children performing particularly poorly when identifying this expression (β=-0.08, p=0.032). CONCLUSIONS The current findings show that PLEs are associated with poorer FER. Further work is needed to elucidate causal relationships with implications for the design of future interventions for those at risk of developing psychosis.

Computerized neurocognitive profile in young people with 22q11.2 deletion syndrome compared to youths with schizophrenia and At‐Risk for psychosis

Adults with 22q11.2 Deletion syndrome (22q11DS) have increased prevalence of schizophrenia features. Our goal is to compare the neurocognitive profile in 22q11DS, schizophrenia and individuals at risk for schizophrenia. Twenty‐one 22q11DS patients (8–32 years, mean 14.9 years, 15M, 6F) were matched to four comparison groups on age: low risk (n = 21), first‐degree family members of schizophrenia patients (genetic risk, n = 20), individuals exhibiting putatively prodromal symptoms (clinical risk, n = 19), and patients with schizophrenia (n = 21). All participants received semi‐structured interviews [Diagnostic Interview for Genetic Studies (DIGS) and the Structured Interview for Prodromal Syndromes (SIPS)], and a computerized neurocognitive battery (CNB) measuring the following domains: Abstraction and Mental Flexibility, Attention, Working Memory, Verbal Memory, Face Memory, Spatial Memory, Language, Spatial Processing, Sensorimotor Dexterity, and Emotion Processing. Sixty percent of 22q11DS participants met SIPS criteria for prodromal symptoms and one participant met criteria for paranoid schizophrenia. Thirty‐eight percent met criteria for Depressive Disorders. All 22q11DS participants successfully completed the CNB. 22q11DS participants were significantly less accurate in nearly all domains, but had similar speed of response compared to the other groups. Their profile resembled that of the psychosis groups in accuracy and speed, except for more pronounced deficits in accuracy for face memory and emotion processing. Subthreshold psychotic symptoms are present in a high proportion of 22q11DS participants. Deficits shown in the CNB are more pronounced for accuracy than speed relative to the psychosis groups with similar profiles. Similar deficits have been described in the 22q11DS population using non‐computerized measures, which require increased testing time.

Do we recognize facial expressions of emotions from persons with schizophrenia

OBJECTIVES Impaired facial emotion expression is central to schizophrenia. Extensive work has quantified these differences, but it remains unclear how patient expressions are perceived by their healthy peers and other non-trained individuals. This study examined how static facial expressions of posed and evoked emotions of patients and controls are recognized by naïve observers. METHODS Facial photographs of 6 persons with stable schizophrenia and 6 matched healthy controls expressing five universal emotions (happy, sad, anger, fear, and disgust) and neutral were selected from a previous data set. Untrained raters (N=420) viewed each photo and identified the expressed emotion. Repeated measures ANOVAs were used to assess differences in accuracy and error patterns between patient and control expressions. RESULTS Expressions from healthy individuals were more accurately identified than those from schizophrenia patients across all conditions, except for posed sadness and evoked neutral faces, in which groups did not differ, and posed fear, in which patient expressions were more accurately identified than control expressions. Analysis of incorrect responses revealed misidentifications as neutral were most common across both groups but significantly more likely among patients. CONCLUSION Present findings demonstrate that patient expressions of emotion are poorly perceived by naïve observers and support the concept of affective flattening in schizophrenia. These results highlight the real world implications of impairments in emotion expression and may shed light on potential mechanisms of impaired social functioning in schizophrenia.

Principal Components of Heritability From Neurocognitive Domains Differ Between Families With Schizophrenia and Control Subjects

Objective: Various measures of neurocognitive function show mean differences among individuals with schizophrenia (SZ), their relatives, and population controls. We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls. Methods: African-Americans with SZ or schizoaffective disorder (SZA) (n = 514), their relatives (n = 1092), and adult controls (n = 300) completed diagnostic interviews and computerized neurocognitive tests. PCH were estimated from 9 neurocognitive domains. Three PCH, PCH1–PCH3, were modeled to determine if status (SZ, relative, and control), other psychiatric covariates, and education were significant predictors of mean values. A small-scale linkage analysis was also conducted in a subset of the sample. Results: PCH1, PCH2, and PCH3 account for 72% of the genetic variance. PCH1 represents 8 of 9 neurocognitive domains, is most highly correlated with spatial processing and emotion recognition, and has unadjusted heritability of 68%. The means for PCH1 differ significantly among SZ, their relatives, and controls. PCH2, orthogonal to PCH1, is most closely correlated with working memory and has an unadjusted heritability of 45%. Mean PCH2 is different only between SZ families and controls. PCH3 apparently represents a heritable component of neurocognition similar across the 3 diagnostic groups. No significant linkage evidence to PCH1–PCH3 or individual neurocognitive measures was discovered. Conclusions: PCH1 is highly heritable and genetically correlated with SZ. It should prove useful in future genetic analyses. Mean PCH2 differentiates SZ families and controls but not SZ and unaffected family members.