Cognition In Schizophrenia Spectrum Disorders Research Articles

Multivariate Association Between Functional Connectivity Gradients and Cognition in Schizophrenia Spectrum Disorders

BackgroundSchizophrenia spectrum disorders (SSDs), which are characterized by social cognitive deficits, have been associated with dysconnectivity in unimodal (e.g., visual, auditory) and multimodal (e.g., default mode and frontoparietal) cortical networks. However, little is known about how such dysconnectivity is related to social and nonsocial cognition and how such brain-behavior relationships associate with clinical outcomes of SSDs. MethodsWe analyzed cognitive (nonsocial and social) measures and resting-state functional magnetic resonance imaging data from the SPINS [Social Processes Initiative in Neurobiology of the Schizophrenia(s)] study (247 stable participants with SSDs and 172 healthy control participants, ages 18–55 years). We extracted gradients from parcellated connectomes and examined the association between the first 3 gradients and the cognitive measures using partial least squares correlation (PLSC). We then correlated the PLSC dimensions with functioning and symptoms in the SSD group. ResultsThe SSD group showed significantly lower differentiation on all 3 gradients. The first PLSC dimension explained 68.53% (p < .001) of the covariance and showed a significant difference between the SSD and the control group (bootstrap p < .05). PLSC showed that all cognitive measures were associated with gradient scores of unimodal and multimodal networks (gradient 1); auditory, sensorimotor, and visual networks (gradient 2); and perceptual networks and the striatum (gradient 3), which were less differentiated in SSDs. Furthermore, the first dimension was positively correlated with negative symptoms and functioning in the SSD group. ConclusionsThese results suggest a potential role of lower differentiation of brain networks in cognitive and functional impairments in SSDs.

Heterogeneity in functional connectivity: Dimensional predictors of individual variability during rest and task fMRI in psychosis

BackgroundIndividuals with schizophrenia spectrum disorders (SSD) often demonstrate cognitive impairments, associated with poor functional outcomes. While neurobiological heterogeneity has posed challenges when examining social cognition in SSD, it provides a unique opportunity to explore brain-behavior relationships. The aim of this study was to investigate the relationship between individual variability in functional connectivity during resting state and the performance of a social task and social and non-social cognition in a large sample of controls and individuals diagnosed with SSD. MethodsNeuroimaging and behavioral data were analyzed for 193 individuals with SSD and 155 controls (total n = 348). Individual variability was quantified through mean correlational distance (MCD) of functional connectivity between participants; MCD was defined as a global ‘variability score’. Pairwise correlational distance was calculated as 1 – the correlation coefficient between a given pair of participants, and averaging distance from one participant to all other participants provided the mean correlational distance metric. Hierarchical regressions were performed on variability scores derived from resting state and Empathic Accuracy (EA) task functional connectivity data to determine potential predictors (e.g., age, sex, neurocognitive and social cognitive scores) of individual variability. ResultsGroup comparison between SSD and controls showed greater SSD MCD during rest (p = 0.00038), while no diagnostic differences were observed during task (p = 0.063). Hierarchical regression analyses demonstrated the persistence of a significant diagnostic effect during rest (p = 0.008), contrasting with its non-significance during the task (p = 0.50), after social cognition was added to the model. Notably, social cognition exhibited significance in both resting state and task conditions (both p = 0.01). ConclusionsDiagnostic differences were more prevalent during unconstrained resting scans, whereas the task pushed participants into a more common pattern which better emphasized transdiagnostic differences in cognitive abilities. Focusing on variability may provide new opportunities for interventions targeting specific cognitive impairments to improve functional outcomes.

Clinical and computational speech measures are associated with social cognition in schizophrenia spectrum disorders.

In this study, we compared three domains of social cognition (emotion processing, mentalizing, and attribution bias) to clinical and computational language measures in 63 participants with schizophrenia spectrum disorders. Based on the active inference model for discourse, we hypothesized that emotion processing and mentalizing, but not attribution bias, would be related to language disturbances. Clinical ratings for speech disturbance assessed disorganized and underproductive dimensions. Computational features included speech graph metrics, use of modal verbs, use of first-person pronouns, cosine similarity of adjacent utterances, and measures of sentiment; these were represented by four principal components. We found that higher clinical ratings for disorganized speech were predicted by greater impairments in both emotion processing and mentalizing, and that these relationships remained significant when accounting for demographic variables, overall psychosis symptoms, and verbal ability. Similarly, a computational speech component reflecting insular speech was consistently predicted by impairment in emotion processing. There were notable trends for computational speech components reflecting underproductive speech and decreased content-rich speech predicting mentalizing ability. Exploratory longitudinal analyses in a small subset of participants (n=17) found that improvements in both emotion processing and mentalizing predicted improvements in disorganized speech. Attribution bias did not demonstrate strong relationships with language measures. Altogether, our findings are consistent with the active inference model of discourse and suggest greater emphasis on treatments that target social cognitive and language systems.

0692 Relationships Between Sleep and Social Cognitive Biases in Schizophrenia-Spectrum and Bipolar Disorders

Abstract Introduction People with schizophrenia-spectrum disorders (SSDs) and bipolar disorders (BDs) experience difficulty with social cognition, or the mental processes that underlie social interactions, but determinants of social cognitive impairment are still under investigation. Research suggests that poor sleep quality is related to reduced social cognitive ability in BDs, but it is unclear if sleep quality is related to social cognition in SSDs and if sleep may be related to different types of social cognition (e.g., emotion recognition, biases) in different ways. This study aimed to examine relationships between sleep and different types of social cognition in SSDs and BDs. Given known relationships between blaming and untrustworthiness biases and paranoia in these populations, paranoia was also examined as potential mediator of these relationships. Methods Participants (SSDs n=91; BDs with psychotic features n=87) completed tasks of social cognitive ability (e.g., facial and multi-modal emotion recognition, attributional bias, untrustworthiness bias). Participants self-reported their sleep quality. Paranoia was assessed via clinical interview. Results In the BD group, poor sleep quality (r=-.23, p=.04) and shorter sleep duration (r=-.25, p=.02) were associated with a bias towards untrustworthiness. For those with SSDs, increased use of sleep medication was associated with poorer multi-modal emotion recognition (r=-.22, p=.04). Additionally, poor sleep quality and overall poor sleep were associated with increased blaming (r=.22, p=.03; r=.21, p=.04) and untrustworthiness biases (r=-.24, p=.03; r=-.24, p=.03) in this group. Higher daytime tiredness was also associated with untrustworthiness bias (r=-.23, p=.03) in SSDs. Regarding mediation results, paranoia did serve as a mediator in the relationships between sleep and blaming and untrustworthiness biases across the sample. Conclusion Results suggest that poor sleep quality is linked to increased attributional and untrustworthiness biases, and that these relationships may be at least partially explained by paranoia symptoms. Of note, however, is that indirect effect sizes in mediation models were small. Contrary to expectations, poor sleep quality was not consistently associated with reduced social cognitive ability in the current sample. Findings from the current study require further exploration and replication. Support (if any) This work was supported by the National Institute of Mental Health (grant number R01 MH116902-04 awarded to C.A.D).

A-174 Measurement invariance reveals Brief Assessment of Cognition in Schizophrenia (BACS) Token Motor subtest differs in U.S.-based black and white samples

Abstract Objective: The Brief Assessment of Cognition in Schizophrenia (BACS) is widely used to assess cognition in schizophrenia spectrum disorders (SZ). However, norms were developed using a sample of 85% white and 15% black participants. Validation of the BACS across cultures have yielded mixed results suggesting that subtests may function differently. Measurement invariance can be used to assess item consistency across groups. The present study examined the measurement invariance of six BACS subtests using models with increasing constraints across 2 different U.S.-based cultural groups (i.e., black and white). Methods: Participants were 429 black and 475 white individuals diagnosed with SZ from the Bipolar Schizophrenia Network for Intermediate Phenotypes consortium. Results: The Comparative Fit Index (CFI) was used to assess model fit. A change in CFI between models of increasing constraint (i.e., &amp;lt;/= 0.01) is acceptable (Cheung &amp; Rensvold, 2002). Baseline configural invariance (CFI=.983) was achieved. The CFI of the weak model (CFI=.967) exceeded the cut-off difference suggesting subtests do not achieve weak invariance. Partial invariance tests revealed that the Token Motor subtest was not equivalent across groups, leading to a 5-subtest partial weak invariance model. Conclusions: With the exception of the Token Motor subtest, findings suggest that subtests function similarly across these two racial groups. The Token Motor subtest has both the lowest internal consistancy and factor loadings on the BACS and has been removed from the BACS composite score. Future research should examine the utility of the Token Motor test across clinical and cultural groups.

A nation-wide twin study of social cognition in schizophrenia spectrum disorders

We examined social cognition in 32 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs concordant or discordant for a schizophrenia spectrum diagnosis and healthy control (HC) twin pairs (29 MZ/20 DZ). All participants were recruited through the Danish registers. Patients showed several deficits in the ability to detect sarcasm. Impairments were also observed in the unaffected MZ co-twins, indicating that social cognitive deficits could be a genetic vulnerability indicator of the disease. Worse social cognition was associated with lower intelligence and higher levels of psychopathology in patients.

Adverse Childhood Experiences and Neurocognition in Schizophrenia Spectrum Disorders: Age at First Exposure and Multiplicity Matter.

Adverse childhood experiences (ACEs) might be related to cognitive impairments observed in schizophrenia spectrum disorders (SSD). However, it remains unknown what aspects of ACEs are associated with cognitive impairments in SSD. Therefore, we aimed to investigate the association between various characteristics of ACEs (age at first exposure, severity, and multiplicity) and cognition in SSD and healthy controls (HCs). We enrolled 127 individuals with SSD and 56 HCs. Cognitive performance was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Childhood Experience of Care and Abuse Questionnaire was administered to record a history of ACEs. The following characteristics of ACEs were analyzed: multiplicity, severity, and age at first exposure. Individuals with SSD had significantly lower scores on all RBANS domains. Multiplicity and severity of ACEs were significantly higher in patients with SSD compared to HCs. In both groups, greater multiplicity of ACEs was associated with lower scores of global cognition and delayed memory. Additionally, in subjects with SSD, greater multiplicity and younger age at first exposure were associated with lower scores of attention. The present findings indicate that greater multiplicity and younger age at first exposure are the most important aspects of ACEs contributing to cognitive impairments observed in SSD. Moreover, ACEs might exert differential impact on cognition in SSD and HCs.

A Systematic Review of Cognition-Brain Morphology Relationships on the Schizophrenia-Bipolar Disorder Spectrum.

The nature of the relationship between cognition and brain morphology in schizophrenia-spectrum disorders (SSD) and bipolar disorder (BD) is uncertain. This review aimed to address this, by providing a comprehensive systematic investigation of links between several cognitive domains and brain volume, cortical thickness, and cortical surface area in SSD and BD patients across early and established illness stages. An initial search of PubMed and Scopus databases resulted in 1486 articles, of which 124 met inclusion criteria and were reviewed in detail. The majority of studies focused on SSD, while those of BD were scarce. Replicated evidence for specific regions associated with indices of cognition was minimal, however for several cognitive domains, the frontal and temporal regions were broadly implicated across both recent-onset and established SSD, and to a lesser extent BD. Collectively, the findings of this review emphasize the significance of both frontal and temporal regions for some domains of cognition in SSD, while highlighting the need for future BD-related studies on this topic.

The impact of smoking status on cognition and brain morphology in schizophrenia spectrum disorders.

Cigarette smoking is associated with worse cognition and decreased cortical volume and thickness in healthy cohorts. Chronic cigarette smoking is prevalent in schizophrenia spectrum disorders (SSD), but the effects of smoking status on the brain and cognition in SSD are not clear. This study aimed to understand whether cognitive performance and brain morphology differed between smoking and non-smoking individuals with SSD compared to healthy controls. Data were obtained from the Australian Schizophrenia Research Bank. Cognitive functioning was measured in 299 controls and 455 SSD patients. Cortical volume, thickness and surface area data were analysed from T1-weighted structural scans obtained in a subset of the sample (n = 82 controls, n = 201 SSD). Associations between smoking status (cigarette smoker/non-smoker), cognition and brain morphology were tested using analyses of covariance, including diagnosis as a moderator. No smoking by diagnosis interactions were evident, and no significant differences were revealed between smokers and non-smokers across any of the variables measured, with the exception of a significantly thinner left posterior cingulate in smokers compared to non-smokers. Several main effects of smoking in the cognitive, volume and thickness analyses were initially significant but did not survive false discovery rate (FDR) correction. Despite the general absence of significant FDR-corrected findings, trend-level effects suggest the possibility that subtle smoking-related effects exist but were not uncovered due to low statistical power. An investigation of this topic is encouraged to confirm and expand on our findings.

The Relationship between Negative Symptoms and Both Emotion Management and Non-social Cognition in Schizophrenia Spectrum Disorders.

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.

Oxytocin does not improve emotional prosody recognition in schizophrenia-spectrum disorders

Schizophrenia-spectrum disorders (SSD) are associated with deficits in emotional prosody recognition. Whether administration of oxytocin can improve emotional prosody recognition accuracy in SSD is unknown. Sixty individuals with SSD and ninety-seven controls completed a placebo-controlled, double-blind, cross-over trial examining the effects of oxytocin on emotional prosody recognition accuracy. Compared to controls, SSD was associated with poorer emotional prosody recognition accuracy, regardless of stimulus valence or intensity, suggesting a generalized deficit. Oxytocin had no effect on emotional prosody recognition in either group, which is consistent with previous work suggesting that oxytocin only improves high-level social cognition in SSD.

Does childhood trauma influence cognitive functioning in schizophrenia? The association of childhood trauma and cognition in schizophrenia spectrum disorders.

Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect.

Metabolic Disturbances are Associated With Impaired Social Cognition in Schizophrenia Spectrum Disorders

Metabolic syndrome and diabetes in individuals with schizophrenia have been linked to more severe nonsocial cognitive deficits, but the effect of metabolic disturbances on social cognition in schizophrenia spectrum disorders (SSD) is not well understood.

The role of glutamate and GABA in cognitive dysfunction in schizophrenia and mood disorders – A systematic review of magnetic resonance spectroscopy studies

Epidemiologic, genetic, and neurobiological studies suggest considerable overlap between schizophrenia and mood disorders. Importantly, both disorders are associated with a broad range of cognitive deficits as well as altered glutamatergic and GABAergic neurometabolism. We conducted a systematic review of magnetic resonance spectroscopy (MRS) studies investigating the relationship between glutamatergic and GABAergic neurometabolites and cognition in schizophrenia spectrum disorders and mood disorders. A literature search in Pubmed of studies published before April 15, 2019 was conducted and 37 studies were deemed eligible for systematic review. We found that alterations in glutamatergic and GABAergic neurotransmission have been identified relatively consistently in both schizophrenia and mood disorders. However, because of the vast heterogeneity of published studies in terms of illness stage, medication exposure, MRS acquisition parameters and data post-processing strategies, we still do not understand the relationship between those neurotransmitters and cognitive dysfunction in mental illness, which is a critical initial step for rational drug development. Our findings emphasize the need for coordinated multi-center studies that characterize cognitive function and its biological substrates in large and well-defined clinical populations, using harmonized imaging sequences and analytical methods with the goal to elucidate the underlying pathophysiological mechanisms and to inform future clinical trials.

P.688 Emotional recognition as treatment outcome in first-episode psychosis: Association with HSPA1B polymorphisms

Schizophrenia-spectrum disorders (SSD) are associated with deficits in emotional prosody recognition. Whether administration of oxytocin can improve emotional prosody recognition accuracy in SSD is unknown. Sixty individuals with SSD and ninety-seven controls completed a placebo-controlled, double-blind, cross-over trial examining the effects of oxytocin on emotional prosody recognition accuracy. Compared to controls, SSD was associated with poorer emotional prosody recognition accuracy, regardless of stimulus valence or intensity, suggesting a generalized deficit. Oxytocin had no effect on emotional prosody recognition in either group, which is consistent with previous work suggesting that oxytocin only improves high-level social cognition in SSD.

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.

Traditional test administration and proactive interference undermine visual-spatial working memory performance in schizophrenia-spectrum disorders

ABSTRACTIntroductionWorking-memory (WM) is a core cognitive deficit among individuals with Schizophrenia Spectrum Disorders (SSD). However, the underlying cognitive mechanisms of this deficit are less known. This study applies a modified version of the Corsi Block Test to investigate the role of proactive interference in visuospatial WM (VSWM) impairment in SSD.MethodsHealthy and SSD participants completed a modified version of the Corsi Block Test involving both high (typical ascending set size from 4 to 7 items) and low (descending set size from 7 to 4 items) proactive interference conditions.ResultsThe results confirmed that the SSD group performed worse overall relative to a healthy comparison group. More importantly, the SSD group demonstrated greater VSWM scores under low (Descending) versus high (Ascending) proactive interference; this pattern is opposite to that of healthy participants.ConclusionsThis differential pattern of performance supports that proactive interference associated with the traditional administration format contributes to VSWM impairment in SSD. Further research investigating associated neurocognitive mechanisms and the contribution of proactive interference across other domains of cognition in SSD is warranted.

Treatment of social cognition in schizophrenia: Current status and future directions

Efforts to develop psychosocial interventions that specifically target social cognition in schizophrenia spectrum disorders began nearly two decades ago. The field has matured considerably since then and has engendered a great deal of optimism about this treatment approach. Indeed, the efficacy of social cognitive interventions, especially those that address multiple domains of social cognition, has received substantial support. This article critically evaluates the current evidence for social cognitive interventions, identifies limitations and open questions, and suggests priorities and directions for further research. Limitations of available studies include a frequent lack of methodological rigor, suboptimal selection of endpoints, and sparse evidence for generalization to functional improvements. We highlight several emerging psychosocial and non-psychosocial approaches that may enhance the efficacy of social cognitive interventions and promote generalization to improvements in real world functioning. We conclude that cautious optimism is warranted as the field moves forward into the next wave of social cognitive treatment studies.

Non-verbal behaviour and social cognition in schizophrenia spectrum disorders

Non-verbal behaviour and social cognition in schizophrenia spectrum disorders

Cognitive impairment in schizophrenia spectrum personality

Among the most prevalent and debilitating features of disorders on the schizophrenia spectrum are cognitive impairments. However, the pattern and severity of these impairments differ among individuals and across illnesses. The extent to which cognitive dysfunction occurs throughout the spectrum informs us about the pathophysiology of schizophrenia, the potential for treatment, and implications for the course of the illness. This article reviews the most recent findings on cognition in schizophrenia spectrum disorders, focusing on schizotypal personality disorder. Implications and directions for future research are offered.