Mental health care utilization in individuals with high levels of psychosis-like experiences: Associations with race and potentially traumatic events.

Objective: Racial inequities in mental health care utilization (MHCU) are well documented. Marginalized racial groups are more likely to report psychosis-like experiences (PLEs) and are at elevated risk for racial discrimination and trauma, impacting PLE severity. Little is known about how factors associated with race impact treatment seeking among individuals reporting PLEs. The present study examined associations between race, trauma, discrimination, PLEs, and MHCU among people endorsing high levels of PLEs. Method: Participants were Asian/Asian American, Black/African American, or White/European American college students ages 18-25 years meeting PLE self-report measure cutoff scores (N = 177). Binary logistic and multiple linear regressions were used to examine associations between past, current, and prospective MHCU and race, potentially traumatic events, discrimination, and PLEs. Results: Participants endorsing more PLEs were more likely to report past and current treatment and to be considering future services. Asian/Asian American and Black/African American participants were less likely to endorse past, current, and prospective future mental health care. Potentially traumatic events predicted increased utilization of past treatment. Conclusions: Results suggest service differences among participants, such that Black/African American and Asian/Asian American young adults reporting PLEs were less likely than White/European American counterparts to seek treatment even when accounting for traumatic events and discrimination. These findings highlight the need to further elucidate MHCU among marginalized racial groups experiencing psychosis-like symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Anomalous self-experiences in cognition are negatively associated with neurocognitive functioning in schizophrenia.

INTRODUCTION: Anomalous self-experiences (ASEs) are disturbances in the subjective experience of the self and are common in people with schizophrenia. Theorists have suggested that ASEs may underlie the neurocognitive deficits that are also common in people with schizophrenia; however, few studies have empirically investigated the relationship between these variables. Thus, the current study aimed to determine whether self-reported ASEs, particularly disturbances in cognitive or mental experiences, are meaningfully related to neurocognitive performance in individuals with schizophrenia. METHODS: 48 individuals with schizophrenia and 34 healthy comparison participants completed the Inventory of Psychotic-Like Anomalous Experiences (IPASE), which is composed of five subscales including disturbances in cognition, and the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Participants with schizophrenia performed worse than controls on each MCCB domain and had higher ASE scores on the total IPASE and all five subscales. Only the IPASE-Cognition subscale was associated with cognitive performance. Specifically, IPASE-Cognition was negatively correlated with scores in attention, visual learning, reasoning, and working memory. CONCLUSIONS: These results suggest that self-reported subjective disturbances in cognition may be meaningfully associated with several objectively-measured domains of neurocognition. Severity of ASEs may therefore be an important consideration when analysing the extent of cognitive deficits in schizophrenia.

Telepsychotherapy with Youth at Clinical High Risk for Psychosis: Clinical Issues and Best Practices during the COVID-19 Pandemic.

Early detection and prevention of psychosis has become an international priority. Much of this work has focused on youth presenting with attenuated symptoms of psychosis-those at Clinical High Risk for psychosis (CHR)-given their elevated probability of developing the full disorder in subsequent years. Individuals at CHR may be prone to exacerbated psychological distress during the COVID-19 pandemic and its subsequent physical isolation measures, due to heightened stress sensitivity and comorbid mental health problems. Telepsychotherapy holds promise for reaching this population, especially during the current COVID-19 outbreak. However, there are limited evidence-based guidelines or interventions for use of telepsychotherapy with this population. In this paper, we review common clinical issues for individuals at CHR and how they might be exacerbated by the COVID-19 pandemic; best practices for treatment and adaptations for telepsychotherapy for individuals at CHR; and highlight real clinical issues that we are currently experiencing in a United States-based specialized CHR clinic as we conduct telepsychotherapy via videoconferencing. We conclude with questions for those in the field to contemplate, as well as potential challenges and benefits in using telepsychotherapy with individuals at CHR and their families.

Ethnoracial Risk Variation Across the Psychosis Continuum in the US: A Systematic Review and Meta-Analysis.

Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking. Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs]). Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022. Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias. Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs. Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies. Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US.

The influence of psychotic-like experiences on intent to seek treatment: Findings from a multi-site community survey of mental health experiences.

Psychotic-like experiences (PLEs) may reflect elevated risk for serious mental illness, including psychosis. Although some studies report an association between PLEs and increased service utilization, there is evidence of unmet need among individuals with PLEs, with few studies exploring the relation between PLEs and intent to seek treatment. Characterizing factors that underlie intent to seek treatment in individuals not otherwise engaged in treatment may assist in determining the role of PLEs and future intentions, and help prioritize symptoms of greatest significance. Non-help-seeking participants ages 16-30 years (nanalysis = 2529) in a multi-site study completed online questionnaires of PLEs (PRIME with distress), depression (CESD), anxiety (STAI), and intention to seek mental health treatment. Associations between PLEs and intent to seek treatment were analyzed through multiple linear regressions. PRIME scores predicted intent to seek treatment, and item-level analyses suggested that this association was driven by items 12 ("going crazy"), 7 (wondering if people may hurt me), 5 (confused if things are real or imagination/dreams), and 1 (odd/unusual things going on). When accounting for the effects of anxiety and depression, PLE sum scores as well as individual experiences remained statistically significant, although effect sizes were negligible. Findings suggest that PLEs can play a role in identifying individuals who intend to seek mental health services and warrant further research in independent samples.

Understanding Associations Between Race/Ethnicity, Experiences of Discrimination, and Psychotic-like Experiences in Middle Childhood.

OBJECTIVE: The present study aimed to examine factors that may account for race/ethnicity differences in psychotic-like experiences (PLEs) in a middle childhood sample, including evidence for experiences of discrimination as a psychosocial mediator of these differences. METHOD: In a sample of 9- to 10-year-olds (N = 10,839) from the Adolescent Brain Cognitive Development Study, we compared PLEs across racial/ethnic groups. We also examined whether experiences of discrimination indirectly linked racial/ethnic identity and PLEs and whether social support moderated this indirect association. RESULTS: Differences between racial/ethnic groups were found in the endorsement of PLEs, such that Black and Hispanic participants endorsed higher levels of PLEs compared with Asian, multiracial/multiethnic, and White participants. These differences were accounted for in part by experiences of discrimination, an indirect effect that was in turn attenuated by increased social support. CONCLUSION: This is the first study to suggest that the experience of discrimination may indirectly link the association between racial/ethnic differences and endorsement of PLEs using the Prodromal Questionnaire-Brief Child Version and additionally that social support may act as a moderator of this mediation. Results provide evidence that social inequities such as racial discrimination may contribute to increases in PLEs. These findings shed further light on the links between structural racism and mental health inequities for people in minoritized groups.

Race Moderates the Relation between Internalized Stigma and Suicidal Thoughts and Behaviors in Youth with Psychosis-Risk Syndromes and Early Psychosis.

Suicide is a leading cause of death among youth on the psychosis spectrum. Internalized mental health stigma is one risk factor for suicide that may be particularly salient for youth with psychosis-risk syndromes and early psychosis. Among this population, Black youth may face exposure to racism-related stressors that may exacerbate the negative effects of internalized stigma. This study examined whether internalized stigma and race interact to predict suicidal thoughts and behaviors (STB) in a help-seeking sample of Black and White adolescents with psychosis-risk syndromes and early psychosis. Findings suggest that Black youth with early psychosis spectrum disorders may be particularly vulnerable to the negative effects of internalized stigma as they pertain to STB. Internalized stigma may therefore represent an important treatment target in suicide prevention efforts among this population.

Internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a help-seeking sample.

Subjective quality of life can be compromised in individuals with psychosis-risk symptoms, with poorer quality of life being associated with worse functioning and later transition to psychosis. Individuals who experience psychosis-related symptoms also tend to endorse more internalized (or self-) mental health stigma when compared to controls, potentially contributing to delays in seeking treatment and increased duration of untreated psychosis, as well as interfering with treatment engagement and retention in those already receiving care. Despite these findings, and the growing recognition for prevention in earlier phases of psychotic illness, few studies have examined the relation between psychosis-risk symptoms, internalized stigma, and subjective quality of life in a younger, help-seeking sample. The present study examined whether internalized stigma mediates the relation between psychosis-risk symptoms and subjective quality of life in a transdiagnostic sample of youth (M age = 17.93, SD = 2.90) at clinical high-risk for psychosis (CHR), with early psychosis, or with non-psychotic disorders (N = 72). Psychosis-risk symptom severity was assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS). Internalized stigma was assessed using the Internalized Stigma of Mental Illness Inventory (ISMI), and subjective quality of life was assessed using the Youth Quality of Life Instrument - Short Form (YQOL-SF). Internalized stigma fully mediated the relation between psychosis-risk symptoms and subjective quality of life across the full sample (p < .05, f2 = 0.06). Findings suggest that internalized stigma may be an important target in efforts to improve quality of life for individuals in early stages of psychosis.

Psychosis-like experiences and resilience: A systematic and critical review of the literature.

Resilience research has documented the ability to cope with traumatic and stressful situations and/or retain functioning given certain risk factors in the context of psychosis. In this study, we conducted the first systematic review of the literature on psychosis-like experiences (PLEs) and resilience. Fifteen articles (from 11 unique study samples) from 10 countries were included in this systematic review, with a total of 11,937 unique study participants. Inclusion criteria were broad, capturing a wide range of individuals with PLEs who have not yet experienced threshold psychosis, such as individuals in the general population with elevated self-reports of PLEs, as well as clinical groups diagnosed by clinician interviews (i.e., clinical- or ultra-high-risk for psychosis [CHR or UHR]). For this review, studies needed to include research aims and empirical research related to resilience, and use an established or author-defined measure of psychological and/or social resilience. Data reporting quality was assessed with the Strengthening the Reporting of Observational Studies in Epidemiology and place of residence, race/ethnicity/culture/language, occupation, gender/sex, religion, education, socioeconomic status, social capital (PROGRESS) guidelines. Study aims and measurement of key variables varied widely, and all studies were cross-sectional. In 73% of the studies, resilience was inversely associated with PLEs or psychosis risk status (e.g., CHR or UHR). Results related to specific resilience subscales were mixed. Author-defined resilience was typically related to internal/psychological resources. Future research, particularly longitudinal research involving multidimensional measurement of resilience (e.g., internal and external factors), along with well-defined theoretical models, are necessary before drawing firm conclusions on resilience and PLEs. We propose a dynamic, multifaceted, developmentally appropriate, and culturally sensitive model of resilience for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

Paced finger-tapping abnormalities in bipolar disorder indicate timing dysfunction.

OBJECTIVES: Theoretical and empirical evidence suggests that impaired time perception and the neural circuitry contributing to internal timing mechanisms may contribute to severe psychiatric disorders, including mood disorders. The structures that are involved in subsecond timing, i.e., cerebellum and basal ganglia, have also been implicated in the pathophysiology of bipolar disorder. However, the timing of subsecond intervals has infrequently been studied in this population. METHODS: Paced finger-tapping tasks have been used to characterize internal timing processes in neuropsychiatric disorders. A total of 42 bipolar disorder patients (25 euthymic, 17 manic) and 42 age-matched healthy controls completed a finger-tapping task in which they tapped in time with a paced (500-ms intertap interval) auditory stimulus (synchronization), then continued tapping without auditory input while attempting to maintain the same pace (continuation). This procedure was followed using the dominant index finger, then with alternating thumbs. RESULTS: Bipolar disorder participants showed greater timing variability relative to controls regardless of pacing stimulus (synchronization versus continuation) or condition (dominant index finger versus alternating thumbs). Decomposition of timing variance into internal clock versus motor implementation components using the Wing-Kristofferson model showed higher clock variability in the bipolar disorder groups compared to controls, with no differences between groups on motor implementation variability. CONCLUSIONS: These findings suggest that internal timing mechanisms are disrupted in bipolar disorder patients, independent of symptom status. Increased clock variability in bipolar disorder may be related to abnormalities in cerebellar function.

Predictors of internalized mental health stigma in a help-seeking sample of youth: The roles of psychosis-spectrum symptoms and family functioning.

Experiencing psychosis-spectrum symptoms is challenging to youth. Among many difficulties, internalized mental health stigma-the internalization of negative stereotypes-can lead to shame and withdrawal. The objective of this study was to better understand the correlates of internalized stigma among a clinical sample of youth with psychosis-spectrum symptoms. Participants (n = 66; 12-25 years old) were referred by community providers in Maryland, United States. Psychosis-spectrum symptoms were measured via the Structured Interview for Psychosis-Risk Syndromes (SIPS); family-functioning was measured via the Family Assessment Device. Interviewers rated participants' social/role functioning via the Global Functioning: Social and Role Scales. Internalized stigma was measured using the Internalized Stigma of Mental Illness (ISMI) total scale and subscales. The sample included 34 individuals at clinical high risk for psychosis, 16 experiencing early psychosis, and 16 help-seeking controls. Regression analyses indicated that unusual beliefs, avolition, role functioning, and lower family-functioning (caregiver-reported) were significantly associated with higher aspects of internalized stigma, controlling for other symptoms and sociodemographics. These models explained 27% of the variance (adjusted R2) in the total ISMI scale and between 15% to 49% of the variance in ISMI-subscales. Among this help-seeking sample, unusual beliefs, avolition, higher role functioning, and lower family-functioning (caregiver-reported) were associated with more internalized stigma. Pending future research with larger samples, therapeutic interventions focused on these factors and their correlates may benefit youth. Future research is needed to determine temporal precedence of these associations. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

From Womb to Neighborhood: A Racial Analysis of Social Determinants of Psychosis in the United States.

The authors examine U.S.-based evidence that connects characteristics of the social environment with outcomes across the psychosis continuum, from psychotic experiences to schizophrenia. The notion that inequitable social and economic systems of society significantly influence psychosis risk through proxies, such as racial minority and immigrant statuses, has been studied more extensively in European countries. While there are existing international reviews of social determinants of psychosis, none to the authors' knowledge focus on factors in the U.S. context specifically-an omission that leaves domestic treatment development and prevention efforts incomplete and underinformed. In this review, the authors first describe how a legacy of structural racism in the United States has shaped the social gradient, highlighting consequential racial inequities in environmental conditions. The authors offer a hypothesized model linking structural racism with psychosis risk through interwoven intermediary factors based on existing theoretical models and a review of the literature. Neighborhood factors, cumulative trauma and stress, and prenatal and perinatal complications were three key areas selected for review because they reflect social and environmental conditions that may affect psychosis risk through a common pathway shaped by structural racism. The authors describe evidence showing that Black and Latino people in the United States suffer disproportionately from risk factors within these three key areas, in large part as a result of racial discrimination and social disadvantage. This broad focus on individual and community factors is intended to provide a consolidated space to review this growing body of research and to guide continued inquiries into social determinants of psychosis in U.S. contexts.

Associations among domains of self-disturbance in schizophrenia.

Self-disturbances are increasingly recognized as important, possibly even central, features of schizophrenia. However, little is known about the associations among different manifestations of self-disturbances. The aims of the current study were threefold. We aimed to (1) replicate previous findings of increased self-disturbances in schizophrenia, (2) correlate manifestations of self-disturbances in schizophrenia across three domains, and (3) correlate self-disturbances with five symptoms domains of schizophrenia, including positive, negative, disorganized symptoms, excitement, and emotional distress. We examined three domains of self-experience, including somatosensation, anomalous self-experiences, and self-concept clarity. Participants included 48 individuals with schizophrenia and 36 non-psychiatric controls. The results of this study replicate previous findings of significantly higher levels of self-disturbances in people with schizophrenia. The results also indicate positive correlations between the domains of anomalous self-experiences and self-concept clarity, but not somatosensation, in individuals with schizophrenia. As well, anomalous self-experiences were positively correlated with positive symptoms, disorganized symptoms, and emotional distress and self-concept clarity was negatively correlated with disorganized symptoms and emotional distress.

The Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE): Development and validation.

Anomalous self-experiences (ASEs) are among the first symptoms to appear in the prodrome, predict the development of psychosis over and above clinical symptoms, and are common in people with schizophrenia. Although there are well-validated phenomenological interviews for assessing ASEs, there are no self-report measures. The current research describes 4 studies designed to develop and validate a new scale to assess ASEs: the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE). In Study 1, an overinclusive item pool was generated based on phenomenological descriptions of ASEs, and items were kept or discarded based on factor loadings in an exploratory factor analysis. Five factors were extracted including disturbances in Cognition, Consciousness, Self-Awareness and Presence, Somatization, and Transitivism/Demarcation. The 5-factor structure was confirmed in Study 2, and the scale showed measurement invariance between sexes. IPASE scores were correlated with self-report and task measures of self-processing including self-concept clarity, self-consciousness, and self-esteem as well as measures of psychotic-like experiences. In Study 3, people with positive schizotypy had higher IPASE scores than a negative schizotypy and comparison group. In Study 4, people with schizophrenia had higher IPASE scores than healthy controls. Overall, the IPASE displayed strong psychometric qualities and is a brief alternative to resource-intensive phenomenological interviews in clinical, at-risk, and general population samples. (PsycINFO Database Record

Anomalous Self-Experiences and positive symptoms are independently associated with emotion processing deficits in schizophrenia.

Social-cognitive models posit a role of Anomalous Self-Experiences (ASEs), disturbances in the subjective experience of the self, in the development and maintenance of psychosis. Theorists have suggested that ASEs may underlie the social-cognitive deficits that are common in people with schizophrenia. Positive symptoms, negative symptoms, and ASEs may interfere with the ability to perceive, use, understand, and manage emotions. In the current study, 45 people with schizophrenia and 28 healthy controls completed the Inventory of Psychotic-Like Anomalous Self-Experiences (IPASE), the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), and were rated on the Positive and Negative Syndrome Scale (PANSS). Participants with schizophrenia had higher IPASE scores and lower MSCEIT scores than the comparison group. In a series of simultaneous regressions, ASEs, but not positive or negative symptoms, were associated with Total MSCEIT scores and the Using Emotions branch score. In contrast, positive symptoms, but not ASEs or negative symptoms were associated with Perceiving and Managing Emotions branches. Both ASEs and positive symptoms independently contributed to Emotional Experiencing scores. The severity of negative symptoms was not associated with deficits in any MSCEIT scores. These results suggest unique roles for ASEs and positive symptoms in emotion processing deficits in people with schizophrenia.

White matter abnormalities of microstructure and physiological noise in schizophrenia.

White matter abnormalities in schizophrenia have been revealed by many imaging techniques and analysis methods. One of the findings by diffusion tensor imaging is a decrease in fractional anisotropy (FA), which is an indicator of white matter integrity. On the other hand, elevation of metabolic rate in white matter was observed from positron emission tomography (PET) studies. In this report, we aim to compare the two structural and functional effects on the same subjects. Our comparison is based on the hypothesis that signal fluctuation in white matter is associated with white matter functional activity. We examined the variance of the signal in resting state fMRI and found significant differences between individuals with schizophrenia and non-psychiatric controls specifically in white matter tissue. Controls showed higher temporal signal-to-noise ratios clustered in regions including temporal, frontal, and parietal lobes, cerebellum, corpus callosum, superior longitudinal fasciculus, and other major white matter tracts. These regions with higher temporal signal-to-noise ratio agree well with those showing higher metabolic activity reported by studies using PET. The results suggest that individuals with schizophrenia tend to have higher functional activity in white matter in certain brain regions relative to healthy controls. Despite some overlaps, the distinct regions for physiological noise are different from those for FA derived from diffusion tensor imaging, and therefore provide a unique angle to explore potential mechanisms to white matter abnormality.

Impaired cerebellar-dependent eyeblink conditioning in first-degree relatives of individuals with schizophrenia.

Consistent with reports of cerebellar structural, functional, and neurochemical anomalies in schizophrenia, robust cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been observed in the disorder. Impaired dEBC is also present in schizotypal personality disorder, an intermediate phenotype of schizophrenia. The present work sought to determine whether dEBC deficits exist in nonpsychotic first-degree relatives of individuals with schizophrenia. A single-cue tone dEBC paradigm consisting of 10 blocks with 10 trials each (9 paired and 1 unpaired trials) was used to examine the functional integrity of cerebellar circuitry in schizophrenia participants, individuals with a first-degree relative diagnosed with schizophrenia, and healthy controls with no first-degree relatives diagnosed with schizophrenia. The conditioned stimulus (a 400ms tone) coterminated with the unconditioned stimulus (a 50ms air puff to the left eye) on paired trials. One relative and 2 healthy controls were removed from further analysis due to declining conditioned response rates, leaving 18 schizophrenia participants, 17 first-degree relatives, and 16 healthy controls. Electromyographic data were subsequently analyzed using growth curve models in hierarchical linear regression. Acquisition of dEBC conditioned responses was significantly impaired in schizophrenia and first-degree relative groups compared with controls. This finding that cerebellar-mediated associative learning deficits are present in first-degree relatives of individuals with schizophrenia provides evidence that dEBC abnormalities in schizophrenia may not be due to medication or course of illness effects. Instead, the present results are consistent with models of schizophrenia positing cerebellar-cortical circuit abnormalities and suggest that cerebellar abnormalities represent a risk marker for the disorder.

Cerebellar-dependent eyeblink conditioning deficits in schizophrenia spectrum disorders.

Accumulating evidence suggests that abnormalities in neural circuitry and timing associated with the cerebellum may play a role in the pathophysiology of schizophrenia. Schizotypal personality disorder (SPD) may be genetically linked to schizophrenia, but individuals with SPD are freer from potential research confounds and may therefore offer insight into psychophysiological correlates of schizophrenia. The present study employed a delay eyeblink conditioning (EBC) procedure to examine cerebellar-dependent learning in schizophrenia, SPD, and healthy control subjects (n = 18 per group) who were matched for age and gender. The conditioned stimulus was a 400-ms tone that coterminated with a 50 ms unconditioned stimulus air puff. Cognitive performance on the Picture Completion, Digit Symbol Coding, Similarities, and Digit Span subscales of the Wechsler Adult Intelligence Scale--Third Edition was also investigated. The schizophrenia and SPD groups demonstrated robust EBC impairment relative to the control subjects; they had significantly fewer conditioned responses (CRs), as well as smaller CR amplitudes. Schizophrenia subjects showed cognitive impairment across subscales compared with SPD and control subjects; SPD subjects showed intermediate performance to schizophrenia and control subjects and performed significantly worse than controls on Picture Completion. Impaired EBC was significantly related to decreased processing speed in schizophrenia spectrum subjects. These findings support the role of altered cortico-cerebellar-thalamic-cortical circuitry in the pathophysiology of schizophrenia spectrum disorders.

Motor deficits in schizophrenia quantified by nonlinear analysis of postural sway.

Motor dysfunction is a consistently reported but understudied aspect of schizophrenia. Postural sway area was examined in individuals with schizophrenia under four conditions with different amounts of visual and proprioceptive feedback: eyes open or closed and feet together or shoulder width apart. The nonlinear complexity of postural sway was assessed by detrended fluctuation analysis (DFA). The schizophrenia group (n = 27) exhibited greater sway area compared to controls (n = 37). Participants with schizophrenia showed increased sway area following the removal of visual input, while this pattern was absent in controls. Examination of DFA revealed decreased complexity of postural sway and abnormal changes in complexity upon removal of visual input in individuals with schizophrenia. Additionally, less complex postural sway was associated with increased symptom severity in participants with schizophrenia. Given the critical involvement of the cerebellum and related circuits in postural stability and sensorimotor integration, these results are consistent with growing evidence of motor, cerebellar, and sensory integration dysfunction in the disorder, and with theoretical models that implicate cerebellar deficits and more general disconnection of function in schizophrenia.