Exploring Heterogeneity on the Wisconsin Card Sorting Test in Schizophrenia Spectrum Disorders: A Cluster Analytical Investigation.

OBJECTIVES: The Wisconsin Card Sorting Test (WCST) is a complex measure of executive function that is frequently employed to investigate the schizophrenia spectrum. The successful completion of the task requires the interaction of multiple intact executive processes, including attention, inhibition, cognitive flexibility, and concept formation. Considerable cognitive heterogeneity exists among the schizophrenia spectrum population, with substantive evidence to support the existence of distinct cognitive phenotypes. The within-group performance heterogeneity of individuals with schizophrenia spectrum disorder (SSD) on the WCST has yet to be investigated. A data-driven cluster analysis was performed to characterise WCST performance heterogeneity. METHODS: Hierarchical cluster analysis with k-means optimisation was employed to identify homogenous subgroups in a sample of 210 schizophrenia spectrum participants. Emergent clusters were then compared to each other and a group of 194 healthy controls (HC) on WCST performance and demographic/clinical variables. RESULTS: Three clusters emerged and were validated via altered design iterations. Clusters were deemed to reflect a relatively intact patient subgroup, a moderately impaired patient subgroup, and a severely impaired patient subgroup. CONCLUSIONS: Considerable within-group heterogeneity exists on the WCST. Identification of subgroups of patients who exhibit homogenous performance on measures of executive functioning may assist in optimising cognitive interventions. Previous associations found using the WCST among schizophrenia spectrum participants should be reappraised. (JINS, 2019, 25, 750-760).

The effects of a muscarinic receptor 1 gene variant on executive and non-executive cognition in schizophrenia spectrum disorders.

Individuals with schizophrenia who are homozygous at the c.267C > A (rs2067477) single nucleotide polymorphism within the muscarinic M1 receptor gene have been reported to perform less well on the Wisconsin Card Sorting Test (WCST). We investigated if rs2067477 genotype variation influenced WCST performance and non-executive cognition cross-diagnostically in a sample of 147 schizophrenia spectrum participants (SSD) and 294 healthy controls. We were unable to detect any significant differences in executive and non-executive cognitive performance across genotype. A broader genetic focus should be considered when investigating the association between the muscarinic system and cognition in SSD.

The effects of a muscarinic receptor 1 gene variant on cortical thickness and surface area in schizophrenia.

Individuals with schizophrenia who are homozygous at the c.267C>A single nucleotide polymorphism (rs2067477) within the cholinergic muscarinic M1 receptor gene have been reported to perform less well on the Wisconsin Card Sorting Test and demonstrate reduced grey matter volume in the right precentral gyrus. We investigated if rs2067477 genotype variation influenced cortical thickness and cortical surface area in a sample of 176 schizophrenia/schizoaffective disorder patients using FreeSurfer. We were unable to detect any significant changes to either surface-based measure of brain structure across genotype. Future studies should expand the focus and include SNPs that are in linkage disequilibrium with rs2067477.

Evidence that eye-movement profiles do not explain slow binocular rivalry rate in bipolar disorder: support for a perceptual endophenotype.

OBJECTIVES: Presenting conflicting images simultaneously, one to each eye, produces perceptual alternations known as binocular rivalry (BR). Slow BR rate has been proposed as an endophenotype for bipolar disorder (BD) for use in large-scale genome-wide association studies. However, the trait could conceivably reflect eye movement (EM) dysfunction in BD rather than anomalous perceptual processing per se. To address this question, we examined the relationship between EM profiles and BR rate for various stimulus types in BD and healthy subjects. We also examined differences in EM profiles between these groups. METHODS: Employing a repeated-measures within-subjects design, 20 BD outpatients and 20 age- and sex-matched healthy controls completed EM tasks and separate BR tasks involving a range of stimuli with different drift speeds. The association between each EM measure and BR rate was examined with correlational analyses for all stimulus conditions in both groups. Between-group comparisons were performed to determine any differences in those EM measures. Corresponding Bayesian analyses were also conducted. RESULTS: There were no EM measures that showed a significant relationship with BR rate in either the BD group or the healthy group (P≥7.87×10-3 ), where those EM measures were also significantly different between the BD and healthy groups (P≥1.32 × 10-2 ). These findings were verified with Bayes factors. CONCLUSIONS: The results provide evidence that EM profiles do not explain the slow BR endophenotype for BD, thus indicating that the trait reflects anomalous perceptual processing per se. This perceptual trait can be employed in clinical, genetic, mechanistic and pathophysiological studies.

No Relationship Between Binocular Rivalry Rate and Eye-Movement Profiles in Healthy Individuals: A Bayes Factor Analysis.

Binocular rivalry (BR) is an intriguing phenomenon in which conflicting images are presented, one to each eye, resulting in perceptual alternations between each image. The rate of BR has been proposed as a potential endophenotype for bipolar disorder because (a) it is well established that this highly heritable psychiatric condition is associated with slower BR rate than in controls, and (b) an individual's BR rate is approximately 50% genetically determined. However, eye movements (EMs) could potentially account for the slow BR trait given EM anomalies are observed in psychiatric populations, and there has been report of an association between saccadic rate and BR rate in healthy individuals. Here, we sought to assess the relationship between BR rate and EMs in healthy individuals (N = 40, mean age = 34.4) using separate BR and EM tasks, with the latter measuring saccades during anticipatory, antisaccade, prosaccade, self-paced, free-viewing, and smooth-pursuit tasks. No correlation was found between BR rate and any EM measure for any BR task (p > .01) with substantial evidence favoring this lack of association (BF(01) > 3). This finding is in contrast to previous data and has important implications for using BR rate as an endophenotype. If replicated in clinical psychiatric populations, EM interpretations of the slow BR trait can be excluded.

Inpatient views and experiences before and after implementing a totally smoke-free policy in the acute psychiatry hospital setting.

In the present study, we examined the views and experiences of patients admitted to an acute psychiatry unit before and after the implementation of a totally smoke-free policy. Forty-six inpatients completed a questionnaire assessing their views before the smoking ban. Another 52 inpatients completed a questionnaire assessing their views and experiences after the smoking ban. Before the totally smoke-free policy, 69.6% smoked, with 67.7% smoking more when admitted to the psychiatry ward. Before the smoking ban, 54.4% reported that the totally smoke-free policy would be 'negative' or 'very negative,' and 30.5% said it would be 'positive' or 'very positive.' After the totally smoke-free policy, 57.7% smoked heavily before hospital (mean cigarettes/day = 24.9), with consumption dramatically reducing following admission to a totally smoke-free psychiatric unit (mean cigarettes/day = 8.3). After the totally smoke-free policy, 36.5% reported that it was 'negative' or 'very negative,' and 50% reported that it was 'positive' or 'very positive.' Overall, inpatients reported improved acceptance of the policy following implementation. Inpatients stated that the most difficult thing about the smoking ban was experiencing increased negative emotions, while the most positive aspect was the improved physical environment of the ward. Inpatients who smoke must be appropriately supported using a range of strategies, and in the present study, we suggest relevant clinical implications.

The muscarinic system, cognition and schizophrenia.

An increasing body of evidence has implicated the central muscarinic system as contributing to a number of symptoms of schizophrenia and serving as a potential target for pharmaceutical interventions. A theoretical review is presented that focuses on the central muscarinic system's contribution to the cognitive symptoms of schizophrenia. The aim is to bridge the void between pertinent neuropsychological and neurobiological research to provide an explanatory account of the role that the central muscarinic system plays in the symptoms of schizophrenia. First, there will be a brief overview of the relevant neuropsychological schizophrenia literature, followed by a concise introduction to the central muscarinic system. Subsequently, we will draw from animal, neuropsychological and pharmacological literature, and discuss the findings in relation to cognition, schizophrenia and the muscarinic system. Whilst unifying the multiple domains of research into a concise review will act as a useful line of enquiry into the central muscarinic systems contribution to the symptoms of schizophrenia, it will be made apparent that more research is needed in this field.

Gender differences in characteristics and outcomes of smokers diagnosed with psychosis participating in a smoking cessation intervention.

While research has identified gender differences in characteristics and outcomes of smokers in the general population, no studies have examined this among smokers with psychosis. This study aimed to explore gender differences among 298 smokers with psychosis (schizophrenia, schizoaffective and bipolar affective disorder) participating in a smoking intervention study. Results revealed a general lack of gender differences on a range of variables for smokers with psychosis including reasons for smoking/quitting, readiness and motivation to quit, use of nicotine replacement therapy, and smoking outcomes including point prevalence or continuous abstinence, and there were no significant predictors of smoking reduction status according to gender at any of the follow-up time-points. The current study did find that female smokers with psychosis were significantly more likely than males to report that they smoked to prevent weight gain. Furthermore, the females reported significantly more reasons for quitting smoking and were more likely to be driven by extrinsic motivators to quit such as immediate reinforcement and social influence, compared to the male smokers with psychosis. Clinical implications include specifically focussing on weight issues and enhancing intrinsic motivation to quit smoking for female smokers with psychosis; and strengthening reasons for quitting among males with psychosis.

The perceived risks and benefits of quitting in smokers diagnosed with severe mental illness participating in a smoking cessation intervention: gender differences and comparison to smokers without mental illness.

INTRODUCTION AND AIMS: This study aimed to examine the perceived risks and benefits of quitting in smokers diagnosed with psychosis, including potential gender differences and comparisons to smokers in the general population. DESIGN AND METHODS: Data were collected from 200 people diagnosed with psychosis participating in a randomised controlled trial testing the effectiveness of a multi-component intervention for smoking cessation and cardiovascular disease risk reduction in people with severe mental illness. Results were compared with both treatment and non-treatment seeking smokers in the general population. RESULTS: Male and female smokers with psychosis generally had similar perceived risks and benefits of quitting. Females rated it significantly more likely that they would experience weight gain and negative affect upon quitting than males diagnosed with psychosis. Compared with smokers in the general population also seeking smoking cessation treatment, this sample of smokers with psychosis demonstrated fewer gender differences and lower ratings of perceived risks and benefits of quitting. The pattern of risk and benefit ratings in smokers diagnosed with psychosis was similar to those of non-treatment seeking smokers in the general population. DISCUSSION AND CONCLUSIONS: These results increase our understanding of smoking in people with severe mental illness, and can directly inform smoking interventions to maximise successful abstinence for this group of smokers. For female smokers with psychosis, smoking cessation interventions need to address concerns regarding weight gain and negative affect. Intervention strategies aimed at enhancing beliefs about the benefits of quitting smoking for both male and female smokers with psychosis are necessary.

Saccadic impairment in schizophrenia with prominent negative symptoms.

Motor disturbances are frequently reported in schizophrenia, particularly in association with negative symptoms, and may reflect frontostriatal dysfunction. This study investigated the timing of self-paced and reprogrammed saccades in 21 patients with schizophrenia, 11 with and 10 without prominent negative symptoms, as compared with 14 healthy controls. Results indicated that schizophrenia patients with increased negative symptoms scores had increased intraindividual variability in their timing of self-paced and reprogrammed saccades and performed saccades with increased peak velocities. It is possible that increased variability may reflect frontostriatal impairments and increased peak velocity may reflect serotonin changes or prefrontal cortex dysfunction.

Estrogen in severe mental illness: a potential new treatment approach.

CONTEXT: Accumulating evidence suggests that estrogens may have therapeutic effects in severe mental illnesses, including schizophrenia, via neuromodulatory and neuroprotective activity. OBJECTIVE: To compare the efficacy of adjunctive transdermal estradiol with that of adjunctive placebo in the treatment of acute psychotic symptoms. DESIGN: Randomized, double-blind study. SETTING: Patients were recruited from inpatient acute hospital wards and outpatient clinics of 2 metropolitan Melbourne general hospitals. PARTICIPANTS: One hundred two women of childbearing age with schizophrenia. All participants were in an acute or chronic phase of their illness; 73 participants were outpatients and the rest were inpatients. Intervention Patients were randomized to receive 100 microg of transdermal estradiol (n = 56) or transdermal placebo (n = 46) for 28 days. MAIN OUTCOME MEASURES: Psychopathological symptoms were assessed weekly with the Positive and Negative Syndrome Scale. RESULTS: The addition of 100 microg of transdermal estradiol significantly reduced positive (P < .05) and general psychopathological (P < .05) symptoms during the 28-day trial period compared with women receiving antipsychotic medication alone. CONCLUSION: Estradiol appears to be a useful treatment for women with schizophrenia and may provide a new adjunctive therapeutic option for severe mental illness. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00206570.