N400 event-related brain potential index of semantic processing and two-year clinical outcomes in persons at high risk for psychosis: A longitudinal study.

The N400 event-related brain potential (ERP) semantic priming effect reflects greater activation of contextually related versus unrelated concepts in long-term semantic memory. Deficits in this measure have been found in persons with schizophrenia and those at clinical high risk (CHR) for this disorder. In CHR patients, we previously found that these deficits predict poorer social functional outcomes after 1 year. In the present study, we tested whether these deficits predicted greater psychosis-spectrum symptom severity and functional impairment over 2 years. We measured N400 semantic priming effects at baseline in CHR patients (n = 47) who viewed prime words each followed by a related/unrelated target word at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured psychosis-spectrum symptoms using the Structured Interview for Prodromal Symptoms and role and social functioning with the Global Functioning: Role and Social scales, at baseline, 1 (n = 29) and 2 years (n = 25). There was a significant interaction between the N400 semantic priming effect at the 300-ms SOA and time on GF:Role scores, indicating that, contrary to expectations, smaller baseline N400 semantic priming effects were associated with more improvement in role functioning from baseline to Year 1, but baseline N400 priming effects did not predict role functioning at Year 2. N400 priming effects were not significantly associated with different trajectories in psychosis-spectrum symptoms or social functioning. Thus, CHR patients' N400 semantic priming effects did not predict clinical outcomes over 2 years, suggesting that this ERP measure may have greater value as a state or short-term prognostic neurophysiological biomarker.

Change in Severity of Mental Disorder of Remand Prisoners: An Observational Group-Based Trajectory Study.

BACKGROUND: Mental disorder is common among prisoners; however, little is known about how illness severity changes during incarceration, and especially to what extent there are different trajectories of change. AIMS: Our aims were to investigate trajectories of illness severity among male and female inmates with serious mental disorders, and to investigate whether clinical or demographic variables are associated with different trajectories. METHODS: We carried out a retrospective cohort study of newly remanded inmates who had three or more serial measures of illness severity as measured by psychiatrists using the Clinical Global Impression-Corrections (CGI-C), and used group-based trajectory modelling to identify trajectories. We investigated whether clinical and demographic variables were associated with different groups. RESULTS: We found an overall reduction in the severity of illness (mean change in CGI-C score -0.74, SD 1.5), with women showing greater improvement than men. We identified three distinct trajectories among men and three among women, all showing improvement in illness severity. Approximately 15% of the entire cohort had full resolution of symptoms, whereas the remainder showed partial improvement. Women, younger inmates, and those with substance use disorders were more likely to have full resolution of symptoms. CONCLUSIONS: Although most prisoners showed improvement, and a small proportion had full resolution of symptoms, a significant number continued to have moderately severe symptoms. There is a need for comprehensive treatment within the detention centre, but also a need for transfer to hospital for those with severe symptoms as improvement within the correctional setting tends to be modest.

Distinct profiles of psychological and neuropsychological functions underlying goal-directed pursuit in schizophrenia.

OBJECTIVES: Several components are known to underlie goal-directed pursuit, including executive, motivational and volitional functions. These were explored in schizophrenia spectrum disorders in order to identify subgroups with distinct profiles. METHODS: Multiple executive, motivational and volitional tests were administered to a sample of outpatients with schizophrenia spectrum diagnoses (n = 59) and controls (n = 63). Research questions included whether distinct profiles exist and whether some functions are impacted disproportionately. These questions were addressed via cluster analysis and profile analysis, respectively. RESULTS: Some such functions were significantly altered in schizophrenia while others were unaffected. Two distinct profiles emerged, one characterized by energizing deficits, reduced reward sensitivity and few subjective complaints; while another was characterized by markedly increased punishment sensitivity, intact reward sensitivity and substantial subjective reporting of avolitional symptoms and boredom susceptibility. CONCLUSION: These findings highlight the importance of considering distinct patterns of strengths and deficits in functions governing goal-directed pursuit in schizophrenia that demarcate identifiable subtypes. These distinctions have implications for treatment, assessment and research.

N400 event-related brain potential and functional outcome in persons at clinical high risk for psychosis: A longitudinal study.

BACKGROUND: The N400 event-related brain potential (ERP) semantic priming effect is thought to reflect activation by meaningful stimuli of related concepts in semantic memory and has been found to be deficient in schizophrenia. We tested the hypothesis that, among individuals at clinical high risk (CHR) for psychosis, N400 semantic priming deficits predict worse symptomatic and functional outcomes after one year. METHODS: We measured N400 semantic priming at baseline in CHR patients (n = 47) and healthy control participants (n = 25) who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchronies (SOAs) of 300 or 750 ms. We measured patients' psychosis-like symptoms with the Scale of Prodromal Symptoms (SOPS) Positive subscale, and academic/occupational and social functioning with the Global Functioning (GF):Role and Social scales, respectively, at baseline and one-year follow-up (n = 29). RESULTS: CHR patients exhibited less N400 semantic priming than controls across SOAs; planned contrasts indicated this difference was significant at the 750-ms but not the 300-ms SOA. In patients, reduced N400 semantic priming at the 750-ms SOA was associated with lower GF:Social scores at follow-up, and greater GF:Social decrements from baseline to follow-up. Patients' N400 semantic priming was not associated with SOPS Positive or GF:Role scores at follow-up, or change in these from baseline to follow-up. CONCLUSIONS: In CHR patients, reduced N400 semantic priming at baseline predicted worse social functioning after one year, and greater decline in social functioning over this period. Thus, the N400 may be a useful prognostic biomarker of real-world functional outcome in CHR patients.

A comparison of men and women referred to provincial correctional mental health services in Ontario, Canada.

BACKGROUND: Women comprise around 15% of admissions to provincial correctional institutions in Canada. Women in custody are known to have a high prevalence of mental health concerns, but little is known about how those referred to mental health services compare with referred men at a similar stage of imprisonment. AIMS: Our aim was to describe and compare clinical, social and demographic characteristics of a complete cohort of custodially remanded men and women who were referred to mental health services while under custodial remand in two correctional institutions. METHODS: We carried out retrospective analysis of data obtained from 4040 men and 1734 provincially detained women referred to mental health services in two correctional centres holding mainly pre-trial prisoners and serving a large mixed urban-rural catchment area in Toronto, Canada over a nearly five-year period. Men and women were first screened using the Brief Jail Mental Health Screen. Those who screened positive were assessed using the Jail Screening Assessment Tool the Brief Psychopathology Rating Scale-Expanded (BPRS-E) and the Clinical Global Impression-Corrections (CGI-C). RESULTS: There were many similarities between men and women, but also some important differences. Women were more socioeconomically disadvantaged than men. More women than men reported having children, yet fewer reported having any form of employment or social supports, although men were more likely to report unstable housing. In addition, women were significantly more likely to have mood and anxiety problems and to be self-harming, but did not differ from men in current psychotic symptoms. We also found differences in patterns of substance use, with a higher proportion of women using heroin and methamphetamines but fewer women having accessed addiction services. CONCLUSIONS: Our findings have implications for clinicians and service planners. They underscore the value of systematic screening for identifying need. More specifically, they suggest need for increased availability of addiction services for women as well as ensuring support for those women who have dependent-age children. Improvement in supports for entry into employment is particularly needed for women, while men are particularly likely to need access to stable housing.

Evidence for the ecological validity of the Brief Jail Mental Health Screen: Positive predictive value among remanded men and women.

BACKGROUND: Individuals with severe mental illness are over-represented in correctional institutions. The scarcity of mental health services in prison settings has increased the demand for tools to screen effectively for mental health need. While the need for sensitivity is widely recognised, there has been less attention to specificity of screening tools. In addition, prior studies have focussed on research-informed diagnostic performance rather than real-world service provision. OBJECTIVE: To examine the performance of the Brief Jail Mental Health Screen (BJMHS) for indicating secondary mental health need in 'real world' conditions. METHODS: Retrospective data were collected from 2977 individuals (2256 male) remanded in either of two correctional facilities in Ontario, Canada, who had been screened on reception as having clinically significant mental health needs by correctional health staff using the BJMHS and examined by specialist mental health staff at triage. The positive predictive value (PPV) of the BJMHS was calculated, using actual secondary mental health service referral as the performance criterion. RESULTS: Overall, the positive predictive value of the BJMHS was 67.2%. It was significantly higher for men (69.5%) than women (60.1%). CONCLUSIONS: While these findings add support to the use of the BJMHS in screening mental health need among people under custodial remand, its false positive rate, particularly among women suggests a need to improve its performance. One potentially important avenue for future research would be whether repeating the screen after an interval prior to specialist referral would improve efficiency.

Patterns and Predictors of Reincarceration among Prisoners with Serious Mental Illness: A Cohort Study: Modèles et prédicteurs de réincarcération chez les prisonniers souffrant de maladie mentale grave : Une étude de cohorte.

BACKGROUND: A small proportion of people who have serious mental illness and rapid and frequent incarcerations account for a disproportionate amount of overall service use and cost. It is important to describe such individuals, so that services can respond more effectively. METHODS: We investigated a cohort of 4,704 incarcerated men and women who were discharged from a correctional mental health service and followed for a median of 535 days. We investigated social, clinical, demographic, and offense characteristics as predictors of return to the service using Cox survival analyses. Secondly, we characterized individuals as high-frequency service users as those who had 3 or more incarcerations during a 1-year period and investigated their characteristics. RESULTS: We found that a higher rate of return to custody was associated with schizophrenia spectrum/bipolar affective disorder (BPAD), personality disorder traits, crack cocaine and methamphetamine use, and unstable housing. Charges of theft/robbery and breach of probation were also positively associated, and sex assault was negatively associated with return to custody. Within a 1-year time period, we found 7.2% of individuals were high-frequency service users, which accounted for 19.5% of all reincarcerations. CONCLUSION: Identification of the characteristics of those with mental illness in custody, especially those who have high-frequency returns to custody, may provide opportunity to target resources more effectively. The primary targets of intervention would be to treat those with schizophrenia/BPAD and substance use problems, particularly those using stimulants, and addressing homelessness. This could reduce the problem of repeated criminalization of the mentally ill and reduce the overall incarceration rate.

Glutathione, the Major Redox Regulator, in the Prefrontal Cortex of Individuals at Clinical High Risk for Psychosis.

Introduction: Oxidative stress and glutathione dysregulation have been implicated in the etiology of schizophrenia. To date, most in vivo studies have investigated alterations in cerebral glutathione levels in patients in which the disorder is already established; however, whether oxidative stress actually predates the onset of psychosis remains unknown. In the current study, we investigated cerebral glutathione levels of antipsychotic-naïve individuals at clinical high risk for psychosis. As exploratory analyses, we also investigated the associations between cerebral glutathione levels and peripheral glutathione peroxidase activity and clinical and neuropsychological measures. Methods: Glutathione levels were measured in the medial prefrontal cortex of 30 clinical high risk (n=26 antipsychotic naïve) and 26 healthy volunteers using 3T proton magnetic resonance spectroscopy. Each participant was assessed for glutathione peroxidase activity in plasma and genotyped for the glutamate cysteine ligase catalytic subunit polymorphism. Results: No significant differences were observed in glutathione levels between clinical high risk and healthy volunteers in the medial prefrontal cortex (F(1,54)=0.001, P =0.98). There were no significant correlations between cerebral glutathione levels and clinical and neuropsychological measures. Similarly, no significant differences were found in peripheral glutathione peroxidase activity between clinical high risk and healthy volunteers (F(1,37)=0.15, P =0.70). However, in clinical high risk, we observed a significant effect of lifetime history of cannabis use on glutathione peroxidase activity (F(1,23)=7.41, P =0.01). Discussion: The lack of significant differences between antipsychotic naïve clinical high risk and healthy volunteers suggests that alterations in glutathione levels in medial prefrontal cortex are not present in the clinical high risk state.

I can't get no satisfaction: potential causes of boredom.

A variety of causes of boredom have been proposed including environmental, motivational, emotional, and cognitive factors. Here, we explore four potential cognitive causes of boredom: inattention, hyperactivity, impulsivity, and executive dysfunction. Specifically, we examine the unique and common associations between these factors and boredom propensity. Recent research has established that the two most commonly used measures of boredom propensity (BPS and BSS) are not measuring the same underlying construct. Thus, a second goal of the present project is to determine the unique and common roles of inattention, hyperactivity, impulsivity and poor executive system functioning in predicting the BPS and BSS specifically. The findings reveal that inattention, hyperactivity and executive dysfunction predict boredom propensity, with shared variance accounting for the greater part of this effect. Further, executive dysfunction and hyperactivity uniquely predict boredom propensity as measured by the BPS and BSS, respectively.

Culturally adapted cognitive behavioral therapy for psychosis (CaCBTp): A review of key features of cultural adaptation and considerations for psychologists.

Cognitive behavioral therapy for psychosis is an effective treatment for psychosis. However, psychosis presents differentially according to an individual's cultural context, and it is currently unclear which methods have been used to formulate culturally adapted cognitive behavioral therapy for psychosis (CaCBTp). The current systematic review examines the approaches to CaCBTp that have been evaluated to date and comments on preliminary evidence for the efficacy of CaCBTp. Key features of CaCBTp interventions are discussed in reference to broader cultural adaptations of psychosocial interventions for psychosis and culturally adapted cognitive behavioral therapy for other disorders. Overall, our results identified 12 studies and highlighted five overarching themes of cultural adaptation that clinicians should integrate into the design of future CaCBTp interventions, including family members in treatment, targeting stigma, relying on spiritual leaders, using multifaceted models of mental health, and ensuring adequate language match. The results of this review also highlight the paucity of literature in global CaCBTp interventions, as only 10 studies examining CaCBTp interventions were found. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A qualitative exploration of the mental health challenges and therapeutic needs of Canadian correctional workers.

Purpose: Correctional work is described as a high-stress environment associated with increased prevalence of mental health disorders in employees. Identifying appropriate healthcare services necessitates investigating the mental health challenges and needs of correctional workers (CWs). Methods: Individual interviews (n = 9; 5 M and 4 W) and a mixed gender focus group (n = 6; 3 M and 3 W) were conducted to gather a general sense of the mental health landscape. Data were analyzed to develop a targeted and comprehensive question guide for gender-specific focus groups (n = 14 unique participants; 6 M and 8 W). Results: Eight themes emerged from the gender-specific focus groups. Themes focusing on work culture described the negative repercussions of job stress and the inability to discuss challenges openly due to confidentiality concerns and feelings of seclusion associated with the CW profession. Men were more likely to be subjected to physical violence and women to emotional and sexual harassment from staff and inmates. Themes related to mental health care described the benefits and limitations of the current services and digital mental healthcare. Stigma and accessibility were notable treatment barriers. Lastly, sector-specific therapy was seen as an important component in enhancing engagement and therapist interaction. Conclusion: The study demonstrates the interconnection between work culture and CW mental health that needs to be acknowledged when addressing mental health care.

N400 event-related brain potential as an index of real-world and neurocognitive function in patients at clinical high risk for schizophrenia.

AIM: The N400 event-related potential is a neurophysiological index of cognitive processing of real-world knowledge. In healthy populations, N400 amplitude is smaller in response to stimuli that are more related to preceding context. This 'N400 semantic priming effect' is thought to reflect activation of contextually related information in semantic memory (SM). N400 semantic priming deficits have been found in schizophrenia, and in patients at clinical high risk (CHR) for this disorder. Because this abnormality in processing relationships between meaningful stimuli could affect ability to navigate everyday situations, we hypothesized it would be associated with real-world functional impairment in CHR patients. Second, we hypothesized it would correlate with global neurocognitive impairment in this group. METHODS: We measured N400 semantic priming in 35 CHR patients who viewed prime words each followed by a related or unrelated target word, at stimulus-onset asynchrony (SOA) of 300 or 750 ms. We measured academic/occupational and social function with the global function (GF): Role and Social scales, and cognitive function with the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: Decreased N400 semantic priming at the 300-ms SOA correlated with lower GF:Role scores. Decreased N400 semantic priming at the 750-ms SOA correlated with lower MCCB composite scores. CONCLUSIONS: Deficits in activating contextually related concepts in SM over short time intervals may contribute to functional impairment in CHR patients. Furthermore, N400 priming deficits over longer intervals may be a biomarker of global cognitive dysfunction in this population. Longitudinal studies are needed to determine whether these deficits are associated with schizophrenia risk within this population.

A Systematic Review of Reviews of Correctional Mental Health Services Using the STAIR Framework.

BACKGROUND: Rising demand for correctional mental health services (CMHS) in recent decades has been a global phenomenon. Despite increasing research, there are major gaps in understanding the best models for CMHS and how to measure their effectiveness, particularly studies that consider the overall care pathways and effectiveness of service responses. The STAIR (Screening, Triage, Assessment, Intervention, and Re-integration) model is an evidence-based framework that defines and measures CMHS as a clinical pathway with a series of measurable, and linked functions. METHOD: We conducted a systematic review of the reviews of CMHS elements employing PRISMA guidelines, organized according to STAIR pillars. We assessed the quality of included studies using the AMSTAR-2 criteria. Narrative reviews were read and results synthesized. RESULTS: We included 26 review articles of which 12 were systematic, metaanalyses, and 14 narrative reviews. Two systematic reviews and seven narrative reviews addressed screening and triage with strong evidence to support specific screening and triage systems. There was no evidence for standardised assessment approaches. Eight systematic reviews and seven narrative reviews addressed interventions providing some evidence to support specific psychosocial interventions. Three systematic reviews and six narrative reviews addressed reintegration themes finding relatively weak evidence to support reintegration methods, with interventions often being jurisdictionally specific and lacking generalizability. CONCLUSIONS: The STAIR framework is a useful way to organize the extant literature. More research is needed on interventions, assessment systems, care pathway evaluations, and reintegration models.

Decreased Gamma Auditory Steady-State Response Is Associated With Impaired Real-World Functioning in Unmedicated Patients at Clinical High Risk for Psychosis.

AIM: Deficits in synchronous, gamma-frequency neural oscillations may contribute to schizophrenia patients' real-world functional impairment and can be measured electroencephalographically using the auditory steady-state response (ASSR). Gamma ASSR deficits have been reported in schizophrenia patients and individuals at clinical high risk (CHR) for developing psychosis. We hypothesized that, in CHR patients, gamma ASSR would correlate with real-world functioning, consistent with a role for gamma synchrony deficits in functional impairment. METHODS: A total of 35 CHR patients rated on Global Functioning: Social and Role scales had EEG recorded while listening to 1-ms, 93-dB clicks presented at 40 Hz in 500-ms trains, in response to which 40-Hz evoked power and intertrial phase-locking factor (PLF) were measured. RESULTS: In CHR patients, lower 40-Hz PLF correlated with lower social functioning. CONCLUSIONS: Gamma synchrony deficits may be a biomarker of real-world impairment at early stages of the schizophrenia disease trajectory.

Delivering an Online Cognitive Behavioral Therapy Program to Address Mental Health Challenges Faced by Correctional Workers and Other Public Safety Personnel: Protocol for a Mixed Methods Study.

BACKGROUND: Public safety personnel have regular and often intense exposure to potentially traumatic events at work, especially workplace violence in the case of correctional workers. Subsequently, correctional workers are at higher risk of developing mental health problems such as posttraumatic stress disorder. Public safety personnel are up to 4 times more likely to experience suicidal ideation, suicidal attempts, and death by suicide compared to the general population. Despite this high prevalence, help-seeking behaviors from public safety personnel are low due to stigma and irregular work hours limiting access to care. Innovative treatments are needed to address these challenges. OBJECTIVE: This study will investigate the efficacy of an electronically delivered cognitive behavioral therapy (e-CBT) program tailored to correctional workers' mental health problems. METHODS: This study is composed of 4 phases. In phase 1, we will interview correctional workers individually and in focus groups to identify personal, social, and cultural factors affecting their mental health and barriers to care. Phase 2 will use the information gathered from the interviews to develop gender- and diagnosis-specific e-CBT modules. These will be presented to a new group of participants who will provide further feedback on their usability and accessibility. In phase 3, we will randomly assign participants to either an e-CBT or treatment as usual arm. The program will be evaluated with validated symptomatology questionnaires and interviews. Phase 4 will use this additional information to fine-tune the e-CBT modules for a larger-scale randomized controlled trial design comparing the e-CBT program to in-person CBT. All e-CBT modules will be delivered through a secure online platform. RESULTS: The study received ethics approval in December 2020, and participant recruitment began in March 2021. Participant recruitment has been conducted through targeted advertisements and physician referrals. To date, there have been 15 participants recruited for Phase 1, and it is expected to conclude in July 2021, with phase 2 beginning in September 2021. Complete data collection and analysis from all phases are expected to conclude by July 2023. Linear and binomial regression (for continuous and categorical outcomes, respectively) will be conducted along with interpretive qualitative methods. CONCLUSIONS: If proven efficacious and feasible, this e-CBT program can provide a high-quality and clinically validated resource to address the mental health problems of correctional workers. Additionally, findings can contribute to the development of innovative treatments for other public safety professions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04666974; https://www.clinicaltrials.gov/ct2/show/NCT04666974. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30845.

Validation of the Clinical Global Impression-Corrections Scale (CGI-C) by Equipercentile Linking to the BPRS-E.

Background: The Clinical Global Impression-Corrections (CGI-C) is an adaptation of the severity scale of the Clinical Global Impression for use in correctional facilities. Although it has been shown to have good inter-rater reliability, there have been no validation studies of this instrument. Method: We analyzed data from 726 initial assessments of persons detained in two correctional facilities and compared clinician's ratings for the CGI-C and modified Brief Psychiatric Rating Scale-Expanded (BPRS-E). We used equipercentile linkage and Spearman correlations to investigate concordance in the total sample, by diagnostic groups, and by gender. Results: We found that the CGI-C scores and BPRS-E scores among persons in remand settings were significantly correlated (ρ = 0.51, p < 0.001) and that correlations were the same for men and women. We found that points of equivalence can be reliably found between the two scales using equipercentile linkage, and that those with psychotic disorders had lower BPRS-E scores than those with mood/anxiety/situational stress for equivalent CGI-C scores. Conclusion: Overall, CGI-C ratings correspond well to BPRS-E ratings for both men and women remand prisoners across diagnoses, and the CGI-C appears to be a valid tool for the assessment of severity of symptoms in this setting.

Negative symptoms in the clinical high-risk state for psychosis: Connection with cognition and primacy in impacting functioning.

AIM: In the clinical high-risk (CHR) state for psychosis, both negative symptoms and lower cognitive function have been associated with poorer daily functioning. Recent evidence suggests that negative symptoms share overlapping variability with cognition and may partially mediate the relationship between cognition and functioning. However, the nature of this overlap is unknown, and the reverse mediation model remains untested leaving the precise nature of these associations unclear. METHODS: In order to clarify these relationships, a sample of community-dwelling youth meeting CHR criteria was collected from a specialty CHR clinic (n = 91, mean age = 21, 63% male). Bootstrapping methods were then applied in a mediation analysis to test both negative symptoms and cognition as independent variables and mediating variables predicting social and role functioning in CHR individuals. Canonical correlation analysis was used to characterize the overlapping variability between negative symptoms and cognition. RESULTS: Support for a primary role of negative symptoms in predicting functioning and cognition was observed. Canonical correlation revealed a single dimension of overlap between the two symptom types (r = .62), represented by a strong correlation between negative symptoms in general and tasks involving verbal working memory, vigilance and social cognition specifically. A single cognitive factor composed primarily of these tasks was found to predict role functioning (adjusted R 2 = .04). CONCLUSIONS: The results highlight the importance of considering specific cognitive mechanisms overlapping with negative symptoms in research and rehabilitative practice in CHR populations, as well as the primary importance of targeting negative symptoms.

Personality traits in psychosis and psychosis risk linked to TSPO expression: a neuroimmune marker.

Personality has been correlated with differences in cytokine expression, an indicator of peripheral inflammation; however, the associations between personality and central markers of inflammation have never been investigated in vivo in humans. Microglia are the resident macrophages of the central nervous system, and the first responders to tissue damage and brain insult. Microglial activation is associated with elevated expression of translocator protein 18kDa (TSPO), which can be imaged with positron emission tomography (PET) to quantify immune activation in the human brain. This study aimed to investigate the association between personality and TSPO expression across the psychosis spectrum. A total of 61 high-resolution [18F]FEPPA PET scans were conducted in 28 individuals at clinical high risk (CHR) for psychosis, 19 First-Episode Psychosis (FEP), and 14 healthy volunteers (HVs), and analyzed using a two-tissue compartment model and plasma input function to obtain a total volume of distribution (VT) as an index of brain TSPO expression (controlling for the rs6971 TSPO polymorphism). Personality was assessed using the Revised NEO Personality Inventory (NEO-PI-R). We found TSPO expression to be specifically associated with neuroticism. A positive association between TSPO expression and neuroticism was found in HVs, in contrast to a nonsignificant, negative association in CHR and significant negative association in FEP. The TSPO-associated neuroticism trait indicates an unexplored connection between neuroimmune activation and personality that varies across the psychosis spectrum.

Relationships between cognitive event-related brain potential measures in patients at clinical high risk for psychosis.

Neurophysiological measures of cognitive functioning that are abnormal in patients with schizophrenia are promising candidate biomarkers for predicting development of psychosis in individuals at clinical high risk (CHR). We examined the relationships among event-related brain potential (ERP) measures of early sensory, pre-attentional, and attention-dependent cognition, in antipsychotic-naïve help-seeking CHR patients (n = 36) and healthy control participants (n = 22). These measures included the gamma auditory steady-state response (ASSR; early sensory); mismatch negativity (MMN) and P3a (pre-attentional); and N400 semantic priming effects - a measure of using meaningful context to predict related items - over a shorter and a longer time interval (attention-dependent). Compared to controls, CHR patients had significantly smaller P3a amplitudes (d = 0.62, p = 0.03) and N400 priming effects over the long interval (d = 0.64, p = 0.02). In CHR patients, gamma ASSR evoked power and phase-locking factor were correlated (r = 0.41, p = 0.03). Reductions in mismatch negativity (MMN) and P3a amplitudes were also correlated (r = -0.36, p = 0.04). Moreover, lower gamma ASSR evoked power correlated with smaller MMN amplitudes (r = -0.45, p = 0.02). MMN amplitude reduction was also associated with reduced N400 semantic priming over the shorter but not the longer interval (r = 0.52, p < 0.002). This pattern of results suggests that, in a subset of CHR patients, impairment in pre-attentional measures of early information processing may contribute to deficits in attention-dependent cognition involving rapid, more automatic processing, but may be independent from pathological processes affecting more controlled or strategic processing. Thus, combining neurophysiological indices of cognitive deficits in different domains offers promise for improving their predictive power as prognostic biomarkers of clinical outcome.

The N400 event-related brain potential response: A window on deficits in predicting meaning in schizophrenia.

Schizophrenia is characterized by impairments in using past experience to predict what will happen next, at multiple levels of cognitive processing. The N400 event-related brain potential (ERP) waveform indexes our ability to use contextual information in combination with world knowledge to predict upcoming meaningful or semantic stimuli. N400 studies have provided evidence that patients with schizophrenia have deficits in such prediction. Some studies of schizophrenia patients have found these N400 semantic priming deficits to correlate with delusions, which frequently involve misinterpretations of meaningful relationships between objects or events, and to improve with antipsychotic treatment. Thus, these semantic priming deficits may reflect a neurocognitive mechanism of delusions, paralleling other cognitive domains in which prediction deficits are a proposed cause of schizophrenia symptoms.