Erica Neill

Characterizing cognitive heterogeneity on the schizophrenia–bipolar disorder spectrum

BACKGROUND Current group-average analysis suggests quantitative but not qualitative cognitive differences between schizophrenia (SZ) and bipolar disorder (BD). There is increasing recognition that cognitive within-group heterogeneity exists in both disorders, but it remains unclear as to whether between-group comparisons of performance in cognitive subgroups emerging from within each of these nosological categories uphold group-average findings. We addressed this by identifying cognitive subgroups in large samples of SZ and BD patients independently, and comparing their cognitive profiles. The utility of a cross-diagnostic clustering approach to understanding cognitive heterogeneity in these patients was also explored. METHOD Hierarchical clustering analyses were conducted using cognitive data from 1541 participants (SZ n = 564, BD n = 402, healthy control n = 575). RESULTS Three qualitatively and quantitatively similar clusters emerged within each clinical group: a severely impaired cluster, a mild-moderately impaired cluster and a relatively intact cognitive cluster. A cross-diagnostic clustering solution also resulted in three subgroups and was superior in reducing cognitive heterogeneity compared with disorder clustering independently. CONCLUSIONS Quantitative SZ-BD cognitive differences commonly seen using group averages did not hold when cognitive heterogeneity was factored into our sample. Members of each corresponding subgroup, irrespective of diagnosis, might be manifesting the outcome of differences in shared cognitive risk factors.

Schizotypal Traits are Associated with Poorer Executive Functioning in Healthy Adults.

Previous research has shown mild forms of the neurocognitive impairments seen in schizophrenia among healthy individuals exhibiting high schizotypal traits. This study aimed to explore associations between schizotypy and cognitive performance in an adult community sample. Ninety-five females and 79 males completed the Oxford–Liverpool Inventory of Feelings and Experiences (O-LIFE), which measures four separable aspects of schizotypy: cognitive disorganization, unusual experiences, introvertive anhedonia, and impulsive non-conformity. Subsequently, participants were administered a neurocognitive battery incorporating measures of executive skills including inhibition, cognitive flexibility, reasoning, and problem solving along with measures of attention and processing speed and both verbal and spatial working memory. In line with predictions, the current study found that higher scores on the subscales of unusual experiences, cognitive disorganization, and impulsive non-conformity related to worse performance on a measure of inhibition. Additionally, as introvertive anhedonia increased, both attention and processing speed and reasoning and problem-solving performance became more impaired. In conclusion, this study extends schizotypy literature by examining the subscales of the O-LIFE, and enables inferences to be drawn in relation to cognitive impairment in schizophrenia.

Category fluency in schizophrenia research: Is it an executive or semantic measure?

Introduction The semantic fluency task is described as a measure of semantic function and utilised in schizophrenia (SZ) research to demonstrate semantic deficits. Two meta-analyses support the efficacy of this task in measuring semantic function in SZ; however, a more recent meta-analysis suggests that executive dysfunction is the predominant determinant of semantic fluency performance in this group. By (1) matching the semantic and executive fluency tasks on discriminant validity, and (2) including an additional fluency task containing both semantic and executive elements (animals by size), this study aimed to determine whether semantic fluency is in fact an appropriate measure of semantic function in SZ. Methods Forty-two SZ participants and 40 healthy controls performed 3 fluency tasks: executive (F, A, S), semantic (body parts), and semantic/executive (animals by size). Performance on these tasks was analysed in two ways, (1) based on discriminant validity and (2) by matching output between the semantic and semantic/executive fluency tasks. Results When the semantic and executive fluency tasks were matched, executive fluency performance was either (1) mildly impaired or (2) not impaired in SZ. Both semantic and semantic/executive performance was impaired in SZ regardless of calculation. Group differences on the semantic/executive task remained when executive function was controlled for, but disappeared when semantic fluency effects were controlled for. Conclusions The findings support earlier meta-analyses in finding that the semantic fluency task is a robust measure of semantic memory function in SZ.

Assessing the Relationship between Semantic Processing and Thought Disorder Symptoms in Schizophrenia

Aberrant semantic processing has been linked to the etiology of formal thought disorder (TD) symptoms in schizophrenia. In this cross-sectional study, two prominent theories, overactivation and disorganized structure of semantic memory (SM), were examined in relation to TD symptoms using the continuum approach across two established semantic tasks (direct/indirect semantic priming and categorical fluency). The aim was to examine the validity of the two TD theories in relation to TD symptoms in schizophrenia. Greater direct and indirect priming, fluency productivity and category errors were expected if the data supported the overactivation theory. Reduced fluency productivity and increased category errors would be characteristic of disorganized storage. Fifty-seven schizophrenia/schizoaffective disorder patients and 48 controls completed a clinical assessment and the semantic tasks. There was significantly reduced direct priming in patients compared to controls (p<.05), while indirect priming was not significantly different; there was no association between TD and degree of priming. Patients produced more category-inappropriate words (p<.005) than controls, which was related to increasing severity of circumstantiality. The pattern of results was more indicative of a disorganized SM storage problem in this sample. This phenomenon may underlie some TD symptoms in general schizophrenia. The findings strengthen the relationship between SM deficits and TD symptoms, though this appears to differ between individual symptoms. The authors discuss the value of the continuum approach in addressing research questions in TD etiology. Given low levels of TD in this study, replication of these findings in a sample with greater TD is desirable.

Does cognitive performance map to categorical diagnoses of schizophrenia, schizoaffective disorder and bipolar disorder? A discriminant functions analysis

OBJECTIVES Despite known overlaps in the pattern of cognitive impairments in individuals with bipolar disorder (BD), schizophrenia (SZ) and schizoaffective disorder (SZA), few studies have examined the extent to which cognitive performance validates traditional diagnostic boundaries in these groups. METHOD Individuals with SZ (n=49), schizoaffective disorder (n=33) and BD (n=35) completed a battery of cognitive tests measuring the domains of processing speed, immediate memory, semantic memory, learning, working memory, executive function and sustained attention. RESULTS A discriminant functions analysis revealed a significant function comprising semantic memory, immediate memory and processing speed that maximally separated patients with SZ from those with BD. Initial classification scores on the basis of this function showed modest diagnostic accuracy, owing in part to the misclassification of SZA patients as having SZ. When SZA patients were removed from the model, a second cross-validated classifier yielded slightly improved diagnostic accuracy and a single function solution, of which semantic memory loaded most heavily. CONCLUSIONS A cluster of non-executive cognitive processes appears to have some validity in mapping onto traditional nosological boundaries. However, since semantic memory performance was the primary driver of the discrimination between BD and SZ, it is possible that performance differences between the disorders in this cognitive domain in particular, index separate underlying aetiologies.

Investigating word associations in a schizotypy sample: Contrasting implicit and explicit processing

Introduction Schizotypy is a useful schizophrenia analogue that controls for confounding factors such as medication and general intellectual decline. In the current study this analogue approach was used to examine implicit/explicit and direct/indirect semantic memory function. This is the first study to examine both implicit and explicit semantic access in the same schizotypy sample. Methods Participants completed four semantic tasks: (1) implicit indirect priming, (2) implicit direct priming, (3) explicit object (indirect) task, and (4) explicit association (direct) task. The schizophrenia literature suggests that semantic impairments are associated with thought disorder. As such, participants were divided into low (n=18) and high (n=18) schizotypy groups based on their responses to a thought disorder subscale of the Oxford Liverpool Inventory of Feelings and Experiences (O-Life) scale. Results In terms of implicit performance, the high schizotypy group demonstrated increased direct priming but nonsignificant indirect priming. The low schizotypy group demonstrated no significant difference in direct and indirect priming. Performance on the explicit tasks was equivalent between the two groups for direct stimuli. On the indirect explicit task, high schizotypy was associated with an increase in errors. Conclusions Increased direct priming in high schizotypy is equivalent to that seen in schizophrenia, which has been interpreted as increased spreading of activation. Abnormal performance using the indirect stimuli was found across implicit and explicit versions. The relevance of these findings to schizophrenia are discussed.

Executive functioning in schizophrenia: The result of impairments in lower order cognitive skills?

Executive functioning (EF) impairments are common in schizophrenia. There are two propositions regarding the causes of these impairments: (1) executive impairments are the result of the compounding effects of deficits in lower order cognitive skills (e.g. processing speed, attention) or (2) EF impairments exist in their own right regardless of lower order skills. It is difficult to examine the separable effects of lower order cognitive skills on EF given the overlap required to complete most neuropsychological measures. One battery designed to parcel out the contributions of lower order skills from EF is the Delis-Kaplan Executive Function System (D-KEFS). Inhibition and switching specifically were examined using the D-KEFS versions of the Stroop and Trails task. No group differences in task performance after controlling for lower level skills would provide evidence for a generalised cognitive deficit. Group differences remaining after controlling for these influences would suggest a disproportionate deficit. Results supported both propositions. On both tasks, group differences reflecting slowed reaction time in the schizophrenia group disappeared when lower order skills were controlled for. Differences between groups performance in errors were only evident on the most complex versions of each task with more errors made by the schizophrenia group. These results suggest that (1) both RT and error data are needed to provide a full picture of performance and (2) the relationship between lower order and EF is too complex to provide support for one or the other proposal.

Comparing implicit and explicit semantic access of direct and indirect word pairs in schizophrenia to evaluate models of semantic memory

Semantic memory deficits in schizophrenia (SZ) are profound, yet there is no research comparing implicit and explicit semantic processing in the same participant sample. In the current study, both implicit and explicit priming are investigated using direct (LION-TIGER) and indirect (LION-STRIPES; where tiger is not displayed) stimuli comparing SZ to healthy controls. Based on a substantive review (Rossell and Stefanovic, 2007) and meta-analysis (Pomarol-Clotet et al., 2008), it was predicted that SZ would be associated with increased indirect priming implicitly. Further, it was predicted that SZ would be associated with abnormal indirect priming explicitly, replicating earlier work (Assaf et al., 2006). No specific hypotheses were made for implicit direct priming due to the heterogeneity of the literature. It was hypothesised that explicit direct priming would be intact based on the structured nature of this task. The pattern of results suggests (1) intact reaction time (RT) and error performance implicitly in the face of abnormal direct priming and (2) impaired RT and error performance explicitly. This pattern confirms general findings regarding implicit/explicit memory impairments in SZ whilst highlighting the unique pattern of performance specific to semantic priming. Finally, priming performance is discussed in relation to thought disorder and length of illness.

Using ketamine to model semantic deficits in schizophrenia

Semantic deficits constitute a core cognitive abnormality in schizophrenia. In the current study, the N-methyl-d-aspartate receptor antagonist ketamine was administered to healthy individuals acutely while they performed semantic processing tasks that included word pairs of differing degrees of semantic relatedness. Two dimensions of semantic processing were investigated: (1) explicit versus implicit processing, that is, unconscious versus conscious processing of semantic relationships and (2) direct versus indirect processing, that is, word pairs that are closely (LION-TIGER) or distantly (LION-STRIPES) related. The immediate effects of ketamine (0.8 mg/kg per hour during 80 minutes with approximate target plasma levels of 200 ng/mL) were examined in a placebo-controlled double-blind repeated-measures group design with 19 participants. It was predicted that ketamine would disrupt access to semantic memory as evidenced in schizophrenia, especially the indirectly related word pairs. In addition, implicit processing and explicit processing were predicted to be differentially affected. Ketamine administration did result in an abnormal performance in the reaction time responses to implicitly presented indirectly related word pairs (ie, greater priming) and reduced accuracy for explicit pairs. Performance on the directly related word pair tasks (both implicit and explicit) was similar across ketamine and placebo conditions, except for the suggestion of abnormal semantic matching in the accuracy data in the implicit task. This study confirms that implicit indirect semantic processing is changed under the influences of ketamine akin to schizophrenia. Future research comparing a schizophrenia group and a ketamine group directly about these tasks is needed to determine the similarity of impairments.

Methodological Considerations in the Recruitment and Analysis of Schizotypy Samples

The schizotypy analog allows researchers to control for many of the confounding factors associated with schizophrenia (e.g., medication/illicit drug use and health complications) (1–3). There are, however, still extraneous factors that should be considered when schizotypy samples are employed. The purpose of this article is to highlight some of the areas of consideration including age, education, relative status, abuse history, and religion.