Understanding Cognitive Behavioral Therapy for Psychosis Through the Predictive Coding Framework.

Psychological treatments for persecutory delusions, particularly cognitive behavioral therapy for psychosis, are efficacious; however, mechanistic theories explaining why they work rarely bridge to the level of cognitive neuroscience. Predictive coding, a general brain processing theory rooted in cognitive and computational neuroscience, has increasing experimental support for explaining symptoms of psychosis, including the formation and maintenance of delusions. Here, we describe recent advances in cognitive behavioral therapy for psychosis-based psychotherapy for persecutory delusions, which targets specific psychological processes at the computational level of information processing. We outline how Bayesian learning models employed in predictive coding are superior to simple associative learning models for understanding the impact of cognitive behavioral interventions at the algorithmic level. We review hierarchical predictive coding as an account of belief updating rooted in prediction error signaling. We examine how this process is abnormal in psychotic disorders, garnering noisy sensory data that is made sense of through the development of overly strong delusional priors. We argue that effective cognitive behavioral therapy for psychosis systematically targets the way sensory data are selected, experienced, and interpreted, thus allowing for the strengthening of alternative beliefs. Finally, future directions based on these arguments are discussed.

Delusions are distressing and disabling psychiatric symptoms. Cognitive behavioral therapy for psychosis (CBTp) is the leading psychotherapeutic approach for treating delusions. Predictive coding is a contemporary cognitive neuroscience framework that is increasingly being used to explain mechanisms of delusions. In this article, we attempt to integrate CBTp within the predictive coding framework, outlining how effective CBTp techniques impact aspects of the predictive coding model to contribute to cutting-edge treatment and cognitive neuroscience research on delusions and inform recommendations for treatment advancement.

Belief Updating, Childhood Maltreatment, and Paranoia in Schizophrenia-Spectrum Disorders.

BACKGROUND AND HYPOTHESIS: Exposure to childhood maltreatment-a risk factor for psychosis is associated with paranoia-may impact one's beliefs about the world and how beliefs are updated. We hypothesized that increased exposure to childhood maltreatment is related to volatility-related belief updating, specifically higher expectations of volatility, and that these relationships are strongest for threat-related maltreatment. Additionally, we tested whether belief updating mediates the relationship between maltreatment and paranoia. STUDY DESIGN: Belief updating was measured in 75 patients with schizophrenia-spectrum disorders and 76 nonpsychiatric controls using a 3-option probabilistic reversal learning (3PRL) task. A Hierarchical Gaussian Filter (HGF) was used to estimate computational parameters of belief updating, including prior expectations of volatility (µ03). The Childhood Trauma Questionnaire (CTQ) was used to assess cumulative maltreatment, threat, and deprivation exposure. Paranoia was measured using the Positive and Negative Syndrome Scale (PANSS) and the revised Green et al. Paranoid Thoughts Scale (R-GPTS). RESULTS: Greater exposure to childhood maltreatment is associated with higher prior expectations of volatility in the whole sample and in individuals with schizophrenia-spectrum disorders. This was specific to threat-related maltreatment, rather than deprivation, in schizophrenia-spectrum disorders. Paranoia was associated with both exposure to childhood maltreatment and volatility priors, but we did not observe a significant indirect effect of volatility priors on the relationship between maltreatment and paranoia. CONCLUSIONS: Our study suggests that individuals with schizophrenia-spectrum disorders who were exposed to threatening experiences during childhood expect their environment to be more volatile, potentially facilitating aberrant belief updating and conferring risk for paranoia.

Network Structure of Childhood Trauma, Bodily Disturbances, and Schizotypy in Schizophrenia and Nonclinical Controls.

Background and Hypothesis: Exposure to childhood trauma has been linked to the development of psychosis and bodily self-disturbances, 2 hallmarks of schizophrenia (SZ). Prior work demonstrated that bodily disturbances serve as a bridge between childhood trauma and SZ symptomatology, but the diagnostic specificity of these connections remains unknown. This study uses network analysis to bridge this gap by comparing the interplays between childhood trauma, bodily self-disturbances, and schizotypy in clinical and general populations. Study Design: Networks were constructed to examine the relationships between schizotypy (Schizotypal Personality Questionnaire; SPQ), bodily self-disturbances (Perceptual Aberration Scale; PAS), and childhood trauma (Childhood Trauma Questionnaire, CTQ) in 152 people with SZ and 162 healthy comparison participants (HC). The Fused Graphical Lasso was used to jointly estimate the networks in the 2 groups and the structure and strength of the networks were compared. Node centrality and shortest paths between CTQ, PAS, and schizotypy were examined. Study Results: When comparing SZ and HC, the network of bodily self-disturbances, childhood trauma, and schizotypy were similarly structured, but the network was significantly stronger in SZ than HC. In both groups, bodily self-disturbances were on one of the shortest paths between childhood trauma to schizotypal experiences. Conclusions: Our findings revealed reliable associations between childhood trauma, bodily self-disturbance, and schizotypy, with bodily disturbances acting as a bridge from childhood trauma to schizotypy. The elevated strength of the SZ network indicates a more highly interconnected, and therefore reactive network in which exposure to childhood trauma can more easily activate bodily disturbances and schizotypy.

The insula: Leveraging cellular and systems-level research to better understand its roles in health and schizophrenia.

Schizophrenia is a highly heterogeneous disorder characterized by a multitude of complex and seemingly non-overlapping symptoms. The insular cortex has gained increasing attention in neuroscience and psychiatry due to its involvement in a diverse range of fundamental human experiences and behaviors. This review article provides an overview of the insula's cellular and anatomical organization, functional and structural connectivity, and functional significance. Focusing on specific insula subregions and using knowledge gained from humans and preclinical studies of insular tracings in non-human primates, we review the literature and discuss the functional roles of each subregion, including in somatosensation, interoception, salience processing, emotional processing, and social cognition. Building from this foundation, we then extend these findings to discuss reported abnormalities of these functions in individuals with schizophrenia, implicating insular involvement in schizophrenia pathology. This review underscores the insula's vast role in the human experience and how abnormal insula structure and function could result in the wide-ranging symptoms observed in schizophrenia.

Interplay between childhood trauma, bodily self-disturbances, and clinical phenomena in schizophrenia spectrum disorders: A network analysis.

BACKGROUND: Bodily self-disturbances have long been considered central to schizophrenia. Exposure to childhood trauma has been linked to the development of both psychosis and bodily self-disturbances, yet little work has examined the role of bodily self-disturbances in the relationship between childhood trauma and schizophrenia symptomatology. This study uses network analysis to bridge this gap. METHODS: Networks were constructed to examine relationships between schizophrenia symptoms (Positive and Negative Symptom Scale; PANSS), bodily self-disturbances (Perceptual Aberration Scale; PAS), and self-reported exposure to childhood trauma (Childhood Trauma Questionnaire, Short-Form; CTQ-SF) in 152 people with a schizophrenia-spectrum disorder. Shortest path and bridge analyses were conducted to assess the role of bodily self-disturbances in linking childhood trauma to schizophrenia symptomatology. Three networks were constructed: 1) PAS, childhood trauma, and PANSS sub-scale composites (positive, negative, general); 2) PAS, childhood trauma, and positive symptoms, 3) PAS, childhood trauma, and distress symptoms. RESULTS: Shortest path analysis revealed that bodily self-disturbances were on the shortest path between childhood trauma and positive and general symptoms (Network 1), between trauma and hallucinations (Network 2), and between trauma and depression (Network 3). Bodily self-disturbances were also found to serve as a bridge between childhood trauma and positive symptoms of schizophrenia, particularly delusions and hallucinations. CONCLUSIONS: Using a novel, data-driven approach, we showed that bodily self-disturbances play a key role in linking childhood trauma to positive and co-morbid affective symptoms of schizophrenia. Threat experiences (i.e., abuse) specifically relate to bodily self-disturbances and psychotic symptoms.

Cognitive Control in Schizophrenia: Advances in Computational Approaches.

Psychiatric research is undergoing significant advances in an emerging subspeciality of computational psychiatry, building upon cognitive neuroscience research by expanding to neurocomputational modeling. Here, we illustrate some research trends in this domain using work on proactive cognitive control deficits in schizophrenia as an example. We provide a selective review of formal modeling approaches to understanding cognitive control deficits in psychopathology, focusing primarily on biologically plausible connectionist-level models as well as mathematical models that generate parameter estimates of putatively dissociable psychological or neural processes. We illustrate some of the advantages of these models in terms of understanding both cognitive control deficits in schizophrenia and the potential roles of effort and motivation. Further, we highlight critical future directions for this work, including a focus on establishing psychometric properties, additional work modeling psychotic symptoms and their interaction with cognitive control, and the need to expand both behavioral and neural modeling to samples that include individuals with different mental health conditions, allowing for the examination of dissociable neural or psychological substrates for seemingly similar cognitive impairments across disorders.

Threat Responses in Schizophrenia: A Negative Valence Systems Framework.

PURPOSE OF REVIEW: Emotions are prominent in theories and accounts of schizophrenia but are largely understudied compared to cognition. Utilizing the Research Domain Criteria (RDoC) Negative Valence Systems framework, we review the current knowledge of emotions in schizophrenia. Given the pivotal role of threat responses in theories of schizophrenia and the substantial evidence of altered threat responses, we focus on three components of Negative Valence Systems tied to threat responses: responses to acute threat, responses to potential threat, and sustained threat. RECENT FINDINGS: Individuals with schizophrenia show altered responses to neutral stimuli during acute threat, bed nucleus of the stria terminalis connectivity in response to potential threat, and threat responses associated with sustained threat. Our review concludes that Negative Valence Systems are altered in schizophrenia; however, the level and evidence of alterations vary across the types of threat responses. We suggest avenues for future research to further understand and intervene on threat responses in schizophrenia.

Examining delusional ideation: Relationships with race and socioeconomic status.

Race and socioeconomic status (SES) are commonly cited as risk factors for psychosis and psychotic-like experiences (PLEs). However, few studies have investigated the relationships between race and SES with specific domains of PLEs. Specifically, little work has examined the relationships between race and SES with delusional ideation, severity (preoccupation, conviction, distress), and delusional themes. Using cross-sectional, general population data (N = 727) from the Nathan Kline Institute-Rockland (NKI-Rockland) database, we investigated racial differences in delusional ideation and severity between Black and White participants, including differences in delusional themes. Then, we investigated SES's relationship with delusional thinking and the interaction between race and SES on delusional thinking. Black American participants endorsed higher delusional ideation with stronger severity than White Americans. A significant interaction between race and delusional theme revealed that Black Americans endorse significantly more delusional ideation in themes of grandiosity, religiosity, and referential-guilt. Black Americans endorse greater delusional severity in grandiose and religious ideations. Black Americans endorse stronger preoccupation and conviction - but not distress-in their referential-guilt ideation. SES was not significantly associated with delusional thinking, nor did SES moderate the significant relationships between race and delusional ideation. These results illuminate the clear racial disparity that exist in delusional ideation within a general population, which did not extend to SES in this dataset. Future work should investigate deeper into the contributory factors to these racial disparities, particularly whether they are based in psychological and/or cultural differences or are the result of assessment/measurement bias.

Associations between social engagement, internalizing symptoms, and delusional ideation in the general population.

BACKGROUND: Delusions are a hallmark feature of psychotic disorders and lead to significant clinical and functional impairment. Internalizing symptoms-such as symptoms of depression, anxiety, and trauma exposure-are commonly cited to be related to delusions and delusional ideation and are often associated with deficits in social functioning. While emerging studies are investigating the impact of low social engagement on psychotic-like experiences, little work has examined the relationship between social engagement, internalizing symptoms, and delusional ideation, specifically. METHODS: Using general population data from the Nathan Kline Institute-Rockland (NKI-Rockland) database (N = 526), we examined the relationships between self-reported delusional ideation, internalizing symptoms, and social engagement and tested four indirect effect models to understand how these factors interrelate. RESULTS: Delusional ideation was significantly associated with both increased internalizing symptoms (r = 0.41, p < 0.001) and lower social engagement (r = - 0.14, p = 0.001). Within aspects of social engagement, perceived emotional support showed the strongest relationship with delusional ideation (r = - 0.17, p < 0.001). Lower social engagement was also significantly associated with increased internalizing symptoms (r = - 0.29, p < 0.001). Cross-sectional models suggest that internalizing symptoms have a significant indirect effect on the association between delusional ideation and social engagement. CONCLUSIONS: These findings reveal that elevated delusional ideation in the general population is associated with lower social engagement. Elevated internalizing symptoms appear to play a critical role in reducing engagement, possibly exacerbating delusional thinking. Future work should examine the causal and temporal relationships between these factors.

Relationships between cognitive biases, decision-making, and delusions.

Multiple measures of decision-making under uncertainty (e.g. jumping to conclusions (JTC), bias against disconfirmatory evidence (BADE), win-switch behavior, random exploration) have been associated with delusional thinking in independent studies. Yet, it is unknown whether these variables explain shared or unique variance in delusional thinking, and whether these relationships are specific to paranoia or delusional ideation more broadly. Additionally, the underlying computational mechanisms require further investigation. To investigate these questions, task and self-report data were collected in 88 individuals (46 healthy controls, 42 schizophrenia-spectrum) and included measures of cognitive biases and behavior on probabilistic reversal learning and explore/exploit tasks. Of those, only win-switch rate significantly differed between groups. In regression, reversal learning performance, random exploration, and poor evidence integration during BADE showed significant, independent associations with paranoia. Only self-reported JTC was associated with delusional ideation, controlling for paranoia. Computational parameters increased the proportion of variance explained in paranoia. Overall, decision-making influenced by strong volatility and variability is specifically associated with paranoia, whereas self-reported hasty decision-making is specifically associated with other themes of delusional ideation. These aspects of decision-making under uncertainty may therefore represent distinct cognitive processes that, together, have the potential to worsen delusional thinking across the psychosis spectrum.

Impaired emotional awareness is associated with childhood maltreatment exposure and positive symptoms in schizophrenia.

Objectives: Evidence suggests that emotional awareness-the ability to identify and label emotions-may be impaired in schizophrenia and related to positive symptom severity. Exposure to childhood maltreatment is a risk factor for both low emotional awareness and positive symptoms. Methods: The current investigation examines associations between a performance-based measure of emotional awareness, positive symptom severity, and childhood maltreatment exposure in 44 individuals with a schizophrenia-spectrum disorder and 48 healthy comparison participants using the electronic Levels of Emotional Awareness Scale (eLEAS), Positive and Negative Syndrome Scale (PANSS) and Childhood Trauma Questionnaire (CTQ). Results: Patients demonstrated significant deficits in emotional awareness overall, which was true for both self and others. In patients, lower emotional awareness was significantly associated with more severe positive symptoms. Emotional awareness was significantly impaired in patients with schizophrenia with self-reported maltreatment exposure, relative to other groups. Severity of maltreatment was not significantly associated with emotional awareness or positive symptoms when looking continuously, and there was no significant indirect effect. Conclusion: These data suggest that emotional awareness impairments observed in schizophrenia may be exacerbated by exposure to childhood maltreatment, possibly putting individuals at greater risk for experiencing positive symptoms of psychosis.

Cerebellar Structure and Cognitive Ability in Psychosis.

BACKGROUND: Dysconnectivity theories, combined with advances in fundamental cognitive neuroscience, have led to increased interest in characterizing cerebellar abnormalities in psychosis. Smaller cerebellar gray matter volume has been found in schizophrenia spectrum disorders. However, the course of these deficits across illness stage, specificity to schizophrenia (vs. psychosis more broadly), and relationship to clinical phenotypes, primarily cognitive impairment, remain unclear. METHODS: The Spatially Unbiased Infratentorial toolbox, a gold standard for analyzing human neuroimaging data of the cerebellum, was used to quantify cerebellar volumes and conduct voxel-based morphometry on structural magnetic resonance images obtained from 574 individuals (249 schizophrenia spectrum, 108 bipolar with psychotic features, 217 nonpsychiatric control). Analyses examining diagnosis (schizophrenia spectrum, bipolar disorder), illness stage (early, chronic), and cognitive effects on cerebellum structure in psychosis were performed. RESULTS: Cerebellar structure in psychosis did not differ significantly from healthy participants, regardless of diagnosis and illness stage (effect size = 0.01-0.14). In contrast, low premorbid cognitive functioning was associated with smaller whole and regional cerebellum volumes, including cognitive (lobules VI and VII, Crus I, frontoparietal and attention networks) and motor (lobules I-IV, V, and X; somatomotor network) regions in psychosis (effect size = 0.36-0.60). These effects were not present in psychosis cohorts with average estimated premorbid cognition. CONCLUSIONS: Cerebellar structural abnormalities in psychosis are related to lower premorbid cognitive functioning implicating early antecedents, atypical neurodevelopment, or both in cerebellar dysfunction. Future research focused on identifying the impact of early-life risk factors for psychosis on the development of the cerebellum and cognition is warranted.

Belief Updating and Paranoia in Individuals With Schizophrenia.

BACKGROUND: Persecutory delusions are among the most common delusions in schizophrenia and represent the extreme end of the paranoia continuum. Paranoia is accompanied by significant worry and distress. Identifying cognitive mechanisms underlying paranoia is critical for advancing treatment. We hypothesized that aberrant belief updating, which is related to paranoia in human and animal models, would also contribute to persecutory beliefs in individuals with schizophrenia. METHODS: Belief updating was assessed in 42 participants with schizophrenia and 44 healthy control participants using a 3-option probabilistic reversal learning task. Hierarchical Gaussian Filter was used to estimate computational parameters of belief updating. Paranoia was measured using the Positive and Negative Syndrome Scale and the revised Green et al. Paranoid Thoughts Scale. Unusual thought content was measured with the Psychosis Symptom Rating Scale and the Peters et al. Delusions Inventory. Worry was measured using the Dunn Worry Questionnaire. RESULTS: Paranoia was significantly associated with elevated win-switch rate and prior beliefs about volatility both in schizophrenia and across the whole sample. These relationships were specific to paranoia and did not extend to unusual thought content or measures of anxiety. We observed a significant indirect effect of paranoia on the relationship between prior beliefs about volatility and worry. CONCLUSIONS: This work provides evidence that relationships between belief updating parameters and paranoia extend to schizophrenia, may be specific to persecutory beliefs, and contribute to theoretical models implicating worry in the maintenance of persecutory delusions.

Empathy, Emotion Recognition, and Paranoia in the General Population.

Background: Paranoia is associated with a multitude of social cognitive deficits, observed in both clinical and subclinical populations. Empathy is significantly and broadly impaired in schizophrenia, yet its relationship with subclinical paranoia is poorly understood. Furthermore, deficits in emotion recognition - a very early component of empathic processing - are present in both clinical and subclinical paranoia. Deficits in emotion recognition may therefore underlie relationships between paranoia and empathic processing. The current investigation aims to add to the literature on social cognition and paranoia by: (1) characterizing the relationship between paranoia and empathy, and (2) testing whether there is an indirect effect of emotion recognition on the relationship between empathy and paranoia. Methods: Paranoia, empathy, and emotion recognition were assessed in a non-clinical sample of adults (n = 226) from the Nathan Kline Institute-Rockland (NKI-Rockland) dataset. Paranoia was measured using the Peters Delusions Inventory-21 (PDI-21). Empathy was measured using the Interpersonal Reactivity Index (IRI), a self-report instrument designed to assess empathy using four subscales: Personal Distress, Empathic Concern, Perspective Taking, and Fantasy. Emotion recognition was assessed using the Penn Emotion Recognition Test (ER-40). Structural equation modeling (SEM) was used to estimate relationships between paranoia, the four measures of empathy and emotion recognition. Results: Paranoia was associated with the Fantasy subscale of the IRI, such that higher Fantasy was associated with more severe paranoia (p < 0.001). No other empathy subscales were associated with paranoia. Fantasy was also associated with the emotion recognition of fear, such that higher Fantasy was correlated with better recognition of fear (p = 0.008). Paranoia and emotion recognition were not significantly associated. The Empathic Concern subscale was negatively associated with emotion recognition, with higher empathic concern related to worse overall emotion recognition (p = 0.002). All indirect paths through emotion recognition were non-significant. Discussion: These results suggest that imaginative perspective-taking contributes to paranoia in the general population. These data do not, however, point to robust global relationships between empathy and paranoia or to emotion recognition as an underlying mechanism. Deficits in empathy and emotion recognition observed in schizophrenia may be associated with the broader pathology of schizophrenia, and therefore not detectable with subclinical populations.

Development of Thalamocortical Structural Connectivity in Typically Developing and Psychosis Spectrum Youths.

BACKGROUND: Thalamocortical white matter connectivity is disrupted in psychosis and is hypothesized to play a role in its etiology and associated cognitive impairment. Attenuated cognitive symptoms often begin in adolescence, during a critical phase of white matter and cognitive development. However, little is known about the development of thalamocortical white matter connectivity and its association with cognition. METHODS: This study characterized effects of age, sex, psychosis symptomatology, and cognition in thalamocortical networks in a large sample of youths (N = 1144, ages 8-22 years, 46% male) from the Philadelphia Neurodevelopmental Cohort, which included 316 typically developing youths, 330 youths on the psychosis spectrum, and 498 youths with other psychopathology. Probabilistic tractography was used to quantify percent total connectivity between the thalamus and six cortical regions and assess microstructural properties (i.e., fractional anisotropy) of thalamocortical white matter tracts. RESULTS: Overall, percent total connectivity of the thalamus was weakly associated with age and was not associated with psychopathology or cognition. In contrast, fractional anisotropy of all thalamocortical tracts increased significantly with age, was generally higher in males than females, and was lowest in youths on the psychosis spectrum. Fractional anisotropy of tracts linking the thalamus to prefrontal and posterior parietal cortices was related to better cognitive function across subjects. CONCLUSIONS: By characterizing the pattern of typical development and alterations in those at risk for psychotic disorders, this study provides a foundation for further conceptualization of thalamocortical white matter microstructure as a marker of neurodevelopment supporting cognition and an important risk marker for psychosis.

Characterizing effects of age, sex and psychosis symptoms on thalamocortical functional connectivity in youth.

The thalamus is composed of multiple nuclei densely connected with the cortex in an organized manner, forming parallel thalamocortical networks critical to sensory, motor, and cognitive functioning. Thalamocortical circuit dysfunction has been implicated in multiple neurodevelopmental disorders, including schizophrenia, which also often exhibit sex differences in prevalence, clinical characteristics, and neuropathology. However, very little is known about developmental and sex effects on thalamocortical networks in youth. The present study characterized the effects of age, sex and psychosis symptomatology in anatomically constrained thalamocortical networks in a large community sample of youth (n = 1100, aged 8-21) from the Philadelphia Neurodevelopmental Cohort (PNC). Cortical functional connectivity of seven anatomically defined thalamic nuclear groups were examined: anterior, mediodorsal, ventral lateral, ventral posterolateral, pulvinar, medial and lateral geniculate nuclear groups. Age and sex effects were characterized using complementary thalamic region-of-interest (ROI) to cortical ROI and voxel-wise analyses. Effects of clinical symptomatology were analyzed by separating youth into three groups based on their clinical symptoms; typically developing youth (n = 298), psychosis spectrum youth (n = 320), and youth with other psychopathologies (n = 482). As an exploratory analysis, association with PRIME scores were used as a dimensional measure of psychopathology. Age effects were broadly characterized by decreasing connectivity with sensory/motor cortical areas, and increasing connectivity with heteromodal prefrontal and parietal cortical areas. This pattern was most pronounced for thalamic motor and sensory nuclei. Females showed greater connectivity between multiple thalamic nuclear groups and the visual cortex compared to males, while males showed greater connectivity with the inferior frontal and orbitofrontal cortices. Youth with psychosis spectrum symptoms showed a subtle decrease in thalamic connectivity with the premotor and prefrontal cortices. Across all youth, greater PRIME scores were associated with lower connectivity between the prefrontal cortex and mediodorsal thalamus. By characterizing typical development in anatomically constrained thalamocortical networks, this study provides an anchor for conceptualizing disruptions to the integrity of these networks observed in neurodevelopmental disorders.

Attention-deficit/hyperactivity disorder in youth with psychosis spectrum symptoms.

BACKGROUND: Childhood attention deficit-hyperactivity disorder (ADHD) is common in psychotic disorders. However, prevalence estimates vary widely and the impact of ADHD on the severity of psychotic symptoms and associated features is unclear. We used the Philadelphia Neurodevelopmental Cohort (PNC; n = 9498 youth age 8-21), which includes a comprehensive structured interview of clinical symptoms and the Penn Computerized Neurocognitive Battery (CNB), to clarify the prevalence of ADHD in psychosis spectrum (PS) youth and determine if comorbid ADHD is associated with severity of psychotic symptoms and cognitive impairment. METHODS: Prevalence of ADHD among PS youth was established by comparing PS youth to all other youth in the PNC cohort. Cognition was compared between four groups: typically developing (TD), ADHD, PS without ADHD (PS-ADHD), and PS with ADHD (PS+ADHD). To evaluate the impact of ADHD on psychosis symptomatology, severity of positive and negative psychotic symptoms was compared between PS-ADHD and PS+ADHD groups. RESULTS: ADHD was more prevalent in PS youth compared to non-PS youth (45% vs. 20%). Cognition was significantly impaired in PS youth compared to TD youth, but the presence of ADHD in PS youth was not associated with greater cognitive impairment. Co-morbid ADHD was, however, associated with more severe psychosis symptoms in PS youth. CONCLUSION: ADHD is more common among PS youth compared to youth without PS symptoms and is associated with more severe psychotic symptoms, but not severity of cognitive impairment. The association between ADHD and psychotic disorders may be mediated by psychosis symptoms in youth and may manifest a more stable cognitive impairment.

Insula sub-regions across the psychosis spectrum: morphology and clinical correlates.

The insula is a heterogeneous cortical region, comprised of three cytoarchitecturally distinct sub-regions (agranular, dysgranular, and granular), which traverse the anterior-posterior axis and are differentially involved in affective, cognitive, and somatosensory processing. Smaller insula volume is consistently reported in psychosis-spectrum disorders and is hypothesized to result, in part, from abnormal neurodevelopment. To better understand the regional and diagnostic specificity of insula abnormalities in psychosis, their developmental etiology, and clinical correlates, we characterized insula volume and morphology in a large group of adults with a psychotic disorder (schizophrenia spectrum, psychotic bipolar disorder) and a community-ascertained cohort of psychosis-spectrum youth (age 8-21). Insula volume and morphology (cortical thickness, gyrification, sulcal depth) were quantified from T1-weighted structural brain images using the Computational Anatomy Toolbox (CAT12). Healthy adults (n = 196), people with a psychotic disorder (n = 303), and 1368 individuals from the Philadelphia Neurodevelopmental Cohort (PNC) (381 typically developing (TD), 381 psychosis-spectrum (PS) youth, 606 youth with other psychopathology (OP)), were investigated. Insula volume was significantly reduced in adults with psychotic disorders and psychosis-spectrum youth, following an anterior-posterior gradient across granular sub-regions. Morphological abnormalities were limited to lower gyrification in psychotic disorders, which was specific to schizophrenia and associated with cognitive ability. Insula volume and thickness were associated with cognition, and positive and negative symptoms of psychosis. We conclude that smaller insula volume follows an anterior-posterior gradient in psychosis and confers a broad risk for psychosis-spectrum disorders. Reduced gyrification is specific to schizophrenia and may reflect altered prenatal development that contributes to cognitive impairment.

Paranoia and Grandiosity in the General Population: Differential Associations With Putative Causal Factors.

Worry, negative self-beliefs, and sleep disturbance have been identified as contributory factors to the onset, maintenance, and severity of paranoia. We tested the specificity of these contributory factors to paranoia compared to grandiosity, a different type of delusional ideation. Data were used from 814 adults from the Nathan Kline Institute-Rockland (NKI-Rockland) study, a general population dataset. Paranoid and grandiose delusional ideation was assessed using the Peters Delusions Inventory (PDI-21) and correlated with self-reported worry (n = 228), negative self-beliefs (n = 485), and sleep quality (n = 655). Correlations were compared using Fisher's r-to-z transform to examine whether the magnitude of relationships differed by delusion type. Paranoia was significantly associated with worry, negative self-belief, and sleep quality. Grandiosity demonstrated significantly weaker relationships with worry and negative self-beliefs. Relationships with sleep quality were similar. We replicate previous reports that worry, negative self-beliefs and sleep quality are associated with paranoid ideation in the general population. We extend these findings by demonstrating that these contributory factors, particularly worry and negative self-beliefs, are associated with paranoid ideation to a greater extent than grandiosity. This suggests a degree of specificity of contributory factors to different types of delusional thinking, supporting the pursuit of specific psychological models and treatments for each delusion type.

Disrupted Salience and Cingulo-Opercular Network Connectivity During Impaired Rapid Instructed Task Learning in Schizophrenia.

Rapid instructed task learning (RITL) is the uniquely human ability to transform task information into goal-directed behavior without relying on trial-and-error learning. RITL is a core cognitive process supported by functional brain networks. In patients with schizophrenia, RITL ability is impaired, but the role of functional network connectivity in these RITL deficits is unknown. We investigated task-based connectivity of eight a priori network pairs in participants with schizophrenia (n = 29) and control participants (n = 31) during the performance of an RITL task. Multivariate pattern analysis was used to determine which network connectivity patterns predicted diagnostic group. Of all network pairs, only the connectivity between the cingulo-opercular network (CON) and salience network (SAN) during learning classified patients and control participants with significant accuracy (80%). CON-SAN connectivity during learning was significantly associated with task performance in participants with schizophrenia. These findings suggest that impaired interactions between identification of salient stimuli and maintenance of task goals contributes to RITL deficits in participants with schizophrenia.