White matter tracts differentially associated with auditory hallucinations in first-episode psychosis: A correlational tractography diffusion spectrum imaging study.

Auditory hallucinations (AH) are a debilitating symptom in psychosis, impacting cognition and real world functioning. Recent thought conceptualizes AH as a consequence of long-range brain communication dysfunction, or circuitopathy, within the auditory sensory/perceptual, language, and cognitive control systems. Recently we showed in first-episode psychosis (FEP) that, despite overall intact white matter integrity in the cortical-cortical and cortical-subcortical language tracts and the callosal tracts connecting auditory cortices, the severity of AH correlated inversely with white matter integrity. However, that hypothesis-driven isolation of specific tracts likely missed important white matter concomitants of AH. In this report, we used a whole-brain data-driven dimensional approach using correlational tractography to associate AH severity with white matter integrity in a sample of 175 individuals. Diffusion Spectrum Imaging (DSI) was used to image diffusion distribution. Quantitative Anisotropy (QA) in three tracts was greater with increased AH severity (FDR < 0.001) and QA in three tracts was lower with increased AH severity (FDR < 0.01). White matter tracts showing associations between QA and AH were generally associated with frontal-parietal-temporal connectivity (tracts with known relevance for cognitive control and the language system), in the cingulum bundle, and in prefrontal inter-hemispheric connectivity. The results of this whole brain data-driven analysis suggest that subtle white matter alterations connecting frontal, parietal, and temporal lobes in the service of sensory-perceptual, language/semantic, and cognitive control processes impact the expression of auditory hallucination in FEP. Disentangling the distributed neural circuits involved in AH should help to develop novel interventions, such as non-invasive brain stimulation.

Sleep disorders in veterans with serious mental illnesses: prevalence in Veterans Affairs health record data.

STUDY OBJECTIVES: This study aimed to estimate the 12-month prevalence of diagnosed sleep disorders among veterans with and without serious mental illnesses (SMI) in Veterans Affairs health record data in 2019. We also examined diagnosed sleep disorders across a 9-year period and explored associations with demographic and health factors. METHODS: This study used health record data from VISN 4 of the Veterans Health Administration from 2011 to 2019. SMI diagnoses included schizophrenia and bipolar spectrum diagnoses as well as major depression with psychosis. Sleep diagnoses included insomnias, hypersomnias, sleep-related breathing disorders, circadian rhythm sleep-wake disorders, and sleep-related movement disorders. Demographic and health-related factors were also collected from the record. RESULTS: In 2019, 21.8% of veterans with SMI were diagnosed with a sleep disorder. This is a significantly higher proportion than for veterans without SMI, 15.1% of whom were diagnosed with a sleep disorder. Sleep disorder rates were highest in veterans with a chart diagnosis of major depression with psychosis. From 2011 to 2019, the overall prevalence of sleep disorders in veterans with SMI more than doubled (10.2%-21.8%), suggesting improvements in the detection and diagnosis of sleep concerns for this group. CONCLUSIONS: Our findings suggest that identification and diagnosis of sleep disorders for veterans with SMI has improved over the past decade, though diagnoses still likely underrepresent actual prevalence of clinically relevant sleep concerns. Sleep concerns may be at particularly high risk of going untreated in veterans with schizophrenia-spectrum disorders. CITATION: Bonfils KA, Longenecker JM, Soreca I, et al. Sleep disorders in veterans with serious mental illnesses: prevalence in Veterans Affairs health record data. J Clin Sleep Med. 2023;19(9):1651-1660.

Behavioral Apophenia and Dimensions of Psychoticism in Adolescents with and without Mood Disorders.

Apophenia is the tendency to falsely detect meaningful relationships and may indicate susceptibility to more extreme expressions on the psychotic spectrum. This pilot investigated the fragmented ambiguous object task (FAOT), a new measure designed to assess apophenia behaviorally in a sample of adolescents with and without mood disorders using an image recognition task. Our primary hypothesis was that increased image recognition would be associated with PID-5 psychoticism. Participants were 33 (79% female) adolescents with (n = 18) and without (n = 15) mood disorders. Consistent with predictions, increased recognition of ambiguous images correlated positively with psychoticism. There was also moderate evidence for long-term stability of FAOT apophenia scores over time (mean interval of approximately 10 months). These findings offer preliminary evidence that the FAOT may be reflective of underlying psychoticism in our target population.

Relational memory function in schizophrenia: Electrophysiological evidence for early perceptual and late associative abnormalities.

We used event-related potentials (ERPs) to examine encoding and retrieval during episodic memory in people with schizophrenia (SZ) and biological relatives of SZ (SZr). To isolate contextual from item-specific aspects of memory, we employed the Relational and Item-Specific Encoding (RISE) task. Twenty two healthy controls (HCs), 22 SZ, and 19 SZr, encoded visual depictions of objects when displayed alone (item-specific) or in pairs (relational encoding), and were later tested on recognition of specific objects and whether pairs of objects had appeared together. An early posterior component (P2) during encoding predicted later recognition and was diminished in SZ. A late negative potential (LNP) over left frontal brain regions during recognition was larger for relationally encoded objects than new and item-specific encoded objects in HCs. This pattern was absent for SZ and SZr. Smaller P2 and LNP components were associated with greater self-reported cognitive-perceptual abnormalities. Early posterior brain responses likely relevant to perceptual functions supporting memory formation were diminished in schizophrenia. Late frontal electrophysiological responses associated with relational aspects of memory appear diminished in SZ and SZr, potentially reflecting the influence of genetic liability for schizophrenia on brain functions supporting episodic memory.

Load-dependent functional connectivity deficits during visual working memory in first-episode psychosis.

INTRODUCTION: Aberrant network connectivity is a core deficit in schizophrenia and may underlie many of its associated cognitive deficits. Previous work in first-episode schizophrenia spectrum illness (FESz) suggests preservation of working memory network function during low-load conditions with dysfunction emerging as task complexity increases. This study assessed visual network connectivity and its contribution to load-dependent working memory impairments. METHODS: Magnetoencephalography was recorded from 35 FESz and 28 matched controls (HC) during a lateralized change detection task. Impaired alpha desynchronization was previously identified within bilateral dorsal occipital (Occ) regions. Here, whole-brain alpha-band connectivity was examined using phase-locking (PLV) and bilateral Occ as connectivity seeds. Load effects on connectivity were assessed across participants, and PLV modulation within networks was compared between groups. RESULTS: Occ exhibited significant load modulated connectivity with six regions (FDR-corrected). HC exhibited PLV enhancement with load in all connections. FESz failed to show PLV modulation between right Occ and left inferior frontal gyrus, lateral occipito-temporal sulcus, and anterior intermediate parietal sulcus. Smaller PLVs in all three network connections during both memory load conditions were associated with increased reality distortion in FESz (FDR-corrected.) CONCLUSION: Examination of functional connectivity across the visual working memory network in FESz revealed an inability to enhance communication between perceptual and executive networks in response to increasing cognitive demands. Furthermore, the degree of network communication impairment was associated with positive symptoms. These findings provide insights into the nature of brain dysconnectivity and its contribution to symptoms in early psychosis and identify potential targets for future interventions.

Hierarchical Symptom Components in Early Psychosis.

BACKGROUND AND HYPOTHESIS: Quantitative models of psychopathology can empirically guide subclassification of heterogeneous clinical presentations such as psychosis; they are particularly well-equipped to capture the nuanced symptomatology observed in first-episode psychosis. As well, components may be better aligned with biological variables. The current study sought to confirm and extend knowledge of the hierarchical structure of psychosis symptoms in first-episode psychosis. Based on past hierarchical work, we hypothesized that a 4 component level would be most closely associated with longitudinal disability. STUDY DESIGN: Participants with early-stage psychosis (N = 370) underwent clinical assessment with the scale for the assessment of positive symptoms (SAPS), scale for assessment of negative symptoms (SANS), and global assessment scale(GAS). A subset was assessed at 6 months (N = 221) and 1 year (N = 207). Hierarchical symptom components were extracted at 12 levels. The predictive utility of the components for global functioning was tested. STUDY RESULTS: As predicted, the 4-component model (reality distortion, thought disorder, inexpressivity, apathy/asociality) provided a superior prediction of functioning over other levels of the hierarchy. Baseline apathy/asociality longitudinally predicted functioning beyond the shared variance of the components at 6 months (b = -4.83, t(216) = -5.37, p < .001, R2adj = 0.12) and 1-year (b = -4.49, t(202) = -4.38, p < .001, R2adj = 0.09). CONCLUSIONS: The hierarchical structure of psychotic symptomatology and its external validity have been robustly established in independent, longitudinal first-episode psychosis samples. The established model incorporates multiple levels of granularity that can be flexibly applied based on the level that offers the greatest predictive utility for external validators.

Measuring empathy in groups with high schizotypy: Psychometric evaluation of the Interpersonal Reactivity Index.

Empathy is integral for interpersonal interactions and formation and maintenance of a strong social network. There is wide agreement that empathy is a multidimensional construct, and it is commonly measured with the Interpersonal Reactivity Index (IRI). The IRI is used widely across healthy and clinical populations, yet insufficient evidence exists on whether the IRI is appropriate for use in groups characterized by high levels of schizotypy. This study sought to examine the factor structure and psychometric characteristics of the IRI when used in a sample of participants with high schizotypy. Nine hundred forty-one undergraduates completed the IRI; 218 met criteria for high schizotypy. Confirmatory factor analysis (CFA) was used to test eight a priori factor structures, and scores from the best fitting model were correlated with relevant measures. Of the eight models tested, a two-factor model including the Perspective-Taking and Empathic Concern subscales evidenced the best fit. The original four-factor structure did not meet criteria for adequate fit in our sample. IRI subscale scores correlated with emotional intelligence. Results suggest that a two-factor structure of the IRI is the strongest path forward for use in high schizotypy samples. This approach, in addition to being psychometrically sound, has the added benefit of being a more brief and targeted assessment that aligns well with contemporary models of empathy. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Self-reported perceptual aberrations in psychosis map to event-related potentials and semantic appraisals of objects.

Psychotic disorders have been associated with visual deficits and deviant semantic processing, making it unclear whether object detection abnormalities in psychosis originate from low-level or higher-order visual processes. The current study investigated how high-level visual processing is affected in psychosis by presenting object stimuli with equivalent low-level visual features. Outpatients with affective and nonaffective psychotic disorders, first-degree biological relatives, and psychiatrically unaffected individuals (N = 130) completed the Fragmented Ambiguous Object Task (FAOT) to assess recognition of objects in ambiguous stimuli. During the task, we recorded electroencephalography, quantified event-related potential (ERP) components (P1, N1, negative closure [NCL], N400), and derived four spatiotemporal event-related potential factors using principal components analysis (PCA). In addition to traditional diagnoses, psychosis was characterized using a dimensional measure of individual differences in self-reported sensory experiences (perceptual absorption) calculated from scales that tap the psychotic domain of the hierarchical structure of psychopathology. Rates of detecting objects within fragmented stimuli failed to differ across diagnostic groups or significantly predict perceptual absorption (p = .057). PCA factors that reflected smaller N1 and larger NCL amplitudes were associated with detecting objects. Exploratory analyses revealed that higher perceptual absorption was associated with reductions in the N400 and a late positive PCA factor. Although early and midlatency brain responses modulate during object detection, late brain responses tied to semantic appraisal of objects are related to perceptual aberrations often reported by individuals with severe psychopathology. Dimensional measures of personality appear sensitive to variation in biological systems relevant to psychotic symptomatology and object perception. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cross-Cutting Symptom Domains Predict Functioning in Psychotic Disorders.

OBJECTIVE: Previous research shows elevated disability in psychotic disorders. However, co-occurring symptomatology has been increasingly highlighted as predictive of clinical outcomes in the psychotic spectrum. The current study investigates how both psychotic and nonpsychotic symptom domains predict functioning across psychotic disorders. METHODS: Outpatients (N = 128) with psychotic spectrum diagnoses participated in the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) Field Trials at the Centre for Addiction and Mental Health in Toronto, Canada, in 2011, including the repeated administration of "cross-cutting" brief screening measures that assessed internalizing (eg, anxiety, depression), substance use (eg, alcohol, psychoactive drug use), and psychotic symptoms. Level of functioning was also assessed by self-report and clinician-rated World Health Organization Disability Assessment Schedule 2.0 (WHO-DAS-II). The relation between symptom domains and disability was examined concurrently and prospectively via hierarchical regression. RESULTS: Psychosis was strongly linked to self-reported disability when considered in isolation (ß = 0.22, P < .001; R2 = 0.11). However, when all 3 symptom domains were included in analyses, internalizing symptoms were the strongest concurrent (ß = 0.31, P < .001; R2 = 0.17) and prospective (ß = 0.29, P < .001; R2 = 0.15) predictor of disability. In the concurrent model, an interaction between internalizing and substance use emerged, wherein high internalizing symptoms were particularly detrimental in persons with high levels of substance use (ß = 0.08, P < .05; R2 = 0.014). Results were similar for clinician-rated WHO-DAS-II. CONCLUSIONS: This research supports the potential clinical utility of rapid screening tools available in the newest psychiatric diagnostic manual. The internalizing symptom domain was the strongest predictor of functional outcome for outpatients with psychotic disorders. The results highlight the relevance of a broad range of symptoms, including those that fall outside the primary psychiatric concern, in recovery-oriented clinical work in psychosis.

Apophenia as the disposition to false positives: A unifying framework for openness and psychoticism.

Positive symptoms of schizophrenia and its extended phenotype-often termed psychoticism or positive schizotypy-are characterized by the inclusion of novel, erroneous mental contents. One promising framework for explaining positive symptoms involves apophenia, conceptualized here as a disposition toward false-positive errors. Apophenia and positive symptoms have shown relations to openness to experience (more specifically, to the openness aspect of the broader openness/intellect domain), and all of these constructs involve tendencies toward pattern seeking. Nonetheless, few studies have investigated the relations between psychoticism and non-self-report indicators of apophenia, let alone the role of normal personality variation. The current research used structural equation models to test associations between psychoticism, openness, intelligence, and non-self-report indicators of apophenia comprising false-positive error rates on a variety of computerized tasks. In Sample 1, 1,193 participants completed digit identification, theory of mind, and emotion recognition tasks. In Sample 2, 195 participants completed auditory signal detection and semantic word association tasks. Psychoticism and the openness aspect were positively correlated. Self-reported psychoticism, openness, and their shared variance were positively associated with apophenia, as indexed by false-positive error rates, whether or not intelligence was controlled for. Apophenia was not associated with other personality traits, and openness and psychoticism were not associated with false-negative errors. Findings provide insights into the measurement of apophenia and its relation to personality and psychopathology. Apophenia and pattern seeking may be promising constructs for unifying the openness aspect of personality with the psychosis spectrum and for providing an explanation of positive symptoms. Results are discussed in the context of possible adaptive characteristics of apophenia as well as potential risk factors for the development of psychotic disorders. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Personality traits across the psychosis spectrum: A Hierarchical Taxonomy of Psychopathology conceptualization of clinical symptomatology.

Psychotic disorders have varied clinical presentations, diagnostic stability is poor and other mental disorders often co-occur with the conditions. To improve the clinical and pathophysiological utility of classification systems for psychosis, it is necessary to consider how symptoms may reflect dimensions of psychopathology that extend beyond the boundaries of traditional diagnostic classifications. We examined personality deviation as a means for explaining symptom variation across individuals with serious mental illness. Participants (N = 312) with psychosis, first-degree biological relatives and healthy controls underwent comprehensive clinical evaluations that included symptom ratings and Diagnostic Statistical Manual consensus diagnoses. They completed the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PID-5), which provides multidimensional assessment of personality disturbances and characterizes psychosis-relevant phenomena, and the Schizotypal Personality Questionnaire (SPQ), a widely accepted measure of schizotypal traits. PID-5 was comparable with SPQ in differentiating between participants with and without psychosis. Greater psychotic symptomatology and higher scores on the SPQ Cognitive-perceptual dimension were associated with higher scores on PID-5 Psychoticism. Facet-level traits showed diverse associations with existing clinical syndromes, suggesting they have utility for quantifying separable symptom dimensions that cut across existing disorders. Yet the patient groups were similar across four of the five PID-5 personality trait domains, indicating shared patterns of personality expression that challenge existing categorical delineations. © 2019 John Wiley & Sons, Ltd.

Fragmented ambiguous objects: Stimuli with stable low-level features for object recognition tasks.

Visual object recognition is a complex skill that relies on the interaction of many spatially distinct and specialized visual areas in the human brain. One tool that can help us better understand these specializations and interactions is a set of visual stimuli that do not differ along low-level dimensions (e.g., orientation, contrast) but do differ along high-level dimensions, such as whether a real-world object can be detected. The present work creates a set of line segment-based images that are matched for luminance, contrast, and orientation distribution (both for single elements and for pair-wise combinations) but result in a range of object and non-object percepts. Image generation started with images of isolated objects taken from publicly available databases and then progressed through 3-stages: a computer algorithm generating 718 candidate images, expert observers selecting 217 for further consideration, and naïve observers performing final ratings. This process identified a set of 100 images that all have the same low-level properties but cover a range of recognizability (proportion of naïve observers (N = 120) who indicated that the stimulus "contained a known object") and semantic stability (consistency across the categories of living, non-living/manipulable, and non-living/non-manipulable when the same observers named "known" objects). Stimuli are available at https://github.com/caolman/FAOT.git.

Brain Responses at Encoding Predict Limited Verbal Memory Retrieval by Persons with Schizophrenia.

OBJECTIVE: Special attention has been given to verbal memory deficits in schizophrenia because they are apparent in healthy biological relatives of affected individuals, indicating a link to genetic risk for the disorder. Despite a growing consensus that encoding abnormalities contribute to poor verbal memory in the disorder, few studies have directly examined how neural responses during encoding contribute to later memory performance. METHOD: We evaluated event-related potentials (ERPs) during encoding of verbal material by patients with schizophrenia, healthy first-degree biological relatives of patients, and healthy controls. The extent to which N1, N400, and anterior and parietal Late Positive Components (LPCs) explained encoding accuracy and later memory of material was investigated. RESULTS: Encoding accuracy was associated with asymmetry in anterior LPCs toward right frontal brain regions and was most evident in relatives. N1 was abnormal at encoding in schizophrenia and differentially accounted for later memory performance. In controls better recall of verbal material was predicted by a larger early occipital (N1) encoding response; however, in patients with schizophrenia smaller N1 encoding responses were related to better recall. Interestingly, better recognition of verbal material across groups was also predicted by smaller N1 amplitudes during encoding of word stimuli. CONCLUSION: Separable patterns of electrophysiological response during encoding appear to differentially support recall and recognition of material from memory. Similar patterns of electrophysiological response across patient and relative groups suggest that those who carry genetic liability for schizophrenia share deviations in the neural activity related to encoding of material into episodic memory.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.