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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. (JINS, 2015, 21, 629–638)

Self-report surveys were conducted in Australia between May 2020 and April 2024, allowing for an analysis of perceived psychological resilience in those with and without suicidal ideation (SI) during and after the COVID-19 pandemic. Linear mixed models were used to describe the factors associated with psychological resilience in these populations and in people experiencing transitions between SI states. Of the 1145 people who responded more than once to the survey, 879 (77%) always reported “never SI”, 84 (7%) always reported SI, while 182 (16%) reported SI for only some of their surveys. People who moved between SI states reported significantly lower psychological resilience than those who reported “never SI”, but significantly higher psychological resilience than those reporting SI in all their surveys. For participants always reporting SI, greater psychological resilience was significantly associated with greater hopefulness and quality of life, and less sleep than usual. In people who moved between SI states, greater psychological resilience was significantly associated with greater hopefulness, less psychological distress and lower likelihood of mental illness. Only participants with “never SI” reported better psychological resilience alongside consistent sleep and exercise quantities. These results have important implications for suicide prevention in Australia. However, bidirectional associations require further investigation.

Abstract Background Schizophrenia is associated with deficits in both episodic and semantic memory however, our understanding of how the deficits in each system independently contribute to overall memory performance is poorly understood. The Hopkins Verbal Learning Task (HVLT) is a memory task using a single word list. To perform the task successfully, participants need to use both episodic and semantic abilities. Both episodic and semantic clustering scores can be calculated which provide nuanced information about the memory encoding and retrieval techniques used by those performing the task. Methods Sixty schizophrenia patients and sixty healthy controls were compared in their performance on the HVLT. In addition to analysing immediate recall, learning slope, delayed recall and recognition, semantic and episodic clustering were also compared. Further, given the link between thought disorder and semantic function, this symptom was correlated with memory performance measures. Results The schizophrenia group demonstrated worse performance across learning trials, delayed recall, and recognition indicating a generalised memory problem. Clustering scores were used to probe into semantic and episodic function specifically. The schizophrenia group demonstrated normal episodic clustering in the face of significantly impaired semantic clustering. Further, semantic clustering performance positively correlated with all general memory measures whilst episodic clustering did not. Finally, thought disorder did not correlate with any HVLT performance measure apart from semantic clustering. Discussion It is difficult to tease apart the contributions of semantic and episodic memory impairments to poor overall memory function in schizophrenia. In this study, we have first demonstrated intact episodic clustering in the face of impaired semantic clustering. Then, by correlating semantic and episodic clustering scores with general memory performance measures, we were able to demonstrate that semantic memory performance is more significantly related to overall memory performance than episodic performance. Finally, this result supports the specificity of the relationship between thought disorder and semantic memory impairment.

BackgroundUnusual thought processes, often referred to as delusion proneness, are not unique to clinical populations. Understanding the factors that contribute to delusion proneness has important theoretical and clinical implications in prodromal psychosis.MethodsThis study ascertained the presence of delusion proneness and associated levels of distress, preoccupation and conviction in a large sample of healthy participants (N=258, M= 33.62 years, SD =12.04), and subsequently investigated two aspects of personal worldview in predicting delusion proneness: Locus of control (LOC) and core positive and negative schemas of the self and others. This data was collected via an online survey.ResultsStepwise regression analyses indicated that negative schemas of others predicted the presence of delusion proneness (p<.001) and associated levels of distress (p= .012) and preoccupation (p= .025); whilst negative schemas of the self predicted only the presence of delusion proneness (p= .001). Hierarchical regression analysis demonstrated that LOC was not a significant predictor of the presence of delusion proneness (p= .141), or associated features of distress (p =.281), preoccupation (p=.220) and conviction (p= .660).DiscussionThe current study found that negative schemas of others accounted for more variance in predicting delusion proneness and aspects of experience (distress and preoccupation) than negative self- schemas. Our study may suggest that therapy focusing on one’s regulation of emotions and assumptions about others in individuals with delusion-like beliefs may be more critical in alleviating delusional symptoms than exclusively focusing on self-schemas.

Abstract Background and Hypothesis Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, yet a significant proportion of individuals on clozapine continue to experience disabling symptoms, despite being treated with an adequate dose. There is a need for adjunct treatments to augment clozapine, notably for negative and cognitive symptoms. One such potential agent is the glutathione precursor N-acetylcysteine (NAC). Study Design A randomized double-blind, multi-center, placebo-controlled trial for clozapine patients with enduring psychotic symptoms (n = 84) was undertaken to investigate the efficacy of adjunctive NAC (2 g daily) for negative symptoms, cognition and quality of life (QoL). Efficacy was assessed at 8, 24, and 52 weeks. Study Results NAC did not significantly improve negative symptoms (P = .62), overall cognition (P = .71) or quality of life (Manchester quality of life: P = .11; Assessment of quality of life: P = .57) at any time point over a 1-year period of treatment. There were no differences in reported side effects between the groups (P = .26). Conclusions NAC did not significantly improve schizophrenia symptoms, cognition, or quality of life in treatment-resistant patients taking clozapine. This trial was registered with “Australian and New Zealand Clinical Trials” on the 30 May, 2016 (Registration Number: ACTRN12615001273572).

Abstract Background Semantic and executive dysfunction are among the most prominent of the cognitive impairments in schizophrenia. Using a cluster analysis (CA) approach, the primacy of semantic and executive dysfunction and their relationship to psychopathology was examined in a two-step investigation. Methods In Study One, 76 schizophrenia/schizoaffective disorder (SZ) patients completed three semantic (category fluency productivity, category errors, Hopkins Verbal Learning Test) and three executive function (inhibition, switching, verbal fluency) measures. Three groups were predicted: semantic-dominant (SD), executive-dominant (ED) and mixed. In Study Two, 52 SZ patients and 48 healthy controls completed the MATRICS Consensus Cognitive Battery (MCCB) alongside the previous semantic/executive battery. Results For Study 1, the CA results confirmed the first two specific groups but revealed a third group unimpaired in both domains (UN). Positive and negative symptoms did not differ between all groups. For Study 2, the CA results confirmed the presence of the same three groups: SD, ED and UN. One-way ANOVAs confirmed that MCCB overall cognitive scores for UN group were significantly higher compared to the SD and ED groups, which did not differ from each other; however, all three clinical groups still performed significantly worse than healthy controls. Psychopathology again did not differ between the three clinical groups. Discussion The findings confirm semantic and executive dysfunction as two main areas of cognitive impairment in SZ while also affirming the presence of cognitively impaired patients without these two primary deficits. Symptomatology patterns do not appear to differ between cognitive impairment profiles, highlighting the complexity of symptomatology mechanisms and cognitive deficits being a discrete entity within the illness. These conclusions have implications for the nosology of schizophrenia and the delivery of cognition-based therapies.

BackgroundSchizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample.MethodsParticipants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length.ResultsTwo clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group.ConclusionsThis study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

Most cognitive studies of bipolar disorder (BD) have examined case-control differences on cognitive tests using measures of central tendency, which do not consider intraindividual variability (IIV); a distinct cognitive construct that reliably indexes meaningful cognitive differences between individuals. In this study, we sought to characterize IIV in BD by examining whether it differs from healthy controls (HCs) and is associated with other cognitive measures, clinical variables, and white matter microstructure. Two hundred and seventeen adults, including 100 BD outpatients and 117 HCs, completed processing speed, sustained attention, working memory, and executive function tasks. A subsample of 55 BD participants underwent diffusion tensor imaging. IIV was operationalized as the individual standard deviation in reaction time on the Continuous Performance Test-Identical Pairs version. BD participants had significantly increased IIV compared to age-matched controls. Increased IIV was associated with poorer mean performance scores on processing speed, sustained attention, working memory, and executive function tasks, as well as two whole-brain white matter indices: fractional anisotropy and radial diffusivity. IIV is increased in BD and appears to correlate with other cognitive variables, as well as white matter measures that index reduced structural integrity and demyelination. Thus, IIV may represent a neurobiologically informative cognitive measure for BD research that is worthy of further investigation.

There is ongoing debate regarding the relationship between clinical symptoms and cognition in schizophrenia spectrum disorders (SSD). The present study aimed to explore the potential relationships between symptoms, with an emphasis on negative symptoms, and social and non-social cognition. Hierarchical cluster analysis with k-means optimisation was conducted to characterise clinical subgroups using the Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms in n = 130 SSD participants. Emergent clusters were compared on the MATRICS Consensus Cognitive Battery, which measures non-social cognition and emotion management as well as demographic and clinical variables. Spearman's correlations were then used to investigate potential relationships between specific negative symptoms and emotion management and non-social cognition. Four distinct clinical subgroups were identified: 1. high hallucinations, 2. mixed symptoms, 3. high negative symptoms, and 4. relatively asymptomatic. The high negative symptom subgroup was found to have significantly poorer emotion management than the high hallucination and relatively asymptomatic subgroups. No further differences between subgroups were observed. Correlation analyses revealed avolition-apathy and anhedonia-asociality were negatively correlated with emotion management, but not non-social cognition. Affective flattening and alogia were not associated with either emotion management or non-social cognition. The present study identified associations between negative symptoms and emotion management within social cognition, but no domains of non-social cognition. This relationship may be specific to motivation, anhedonia and apathy, but not expressive deficits. This suggests that targeted interventions for social cognition may also result in parallel improvement in some specific negative symptoms.

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)