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.

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.

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.

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.

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.

Examining the dimensions of schizotypy from the top down: A hierarchical comparison of item-level factor solutions.

Numerous factor analytic studies of the Schizotypal Personality Questionnaire have supported a range of solutions, many with differing numbers of factors. Although some solutions have received more support than others, it remains unclear how clinicians and researchers may evaluate solutions with similar levels of empirical support in relation to one another, and few item-level analyses have been conducted. In the current study, we seek to explore the relationships among various factor solutions in a hierarchical manner using Goldberg's (2006) Bass-Ackward approach. A final sample of 847 undergraduate students completed the Schizotypal Personality Questionnaire with a Likert-style response format. Item-level exploratory factor analyses with between one and nine factors were extracted. Interrelationships among these solutions were examined. Each solution was evaluated in terms of its content, statistical significance, simple structure, and consistency with previous findings. Factor solutions at several levels were found to replicate findings from past factor analyses in terms of individual factor content and relative merit. Solutions with between four and six factors received the most support and solutions with up to seven factors were found to achieve support. (PsycINFO Database Record

Boredom proneness predicts quality of life in outpatients diagnosed with schizophrenia-spectrum disorders.

BACKGROUND: There is increasing recognition of the clinical significance of boredom associated with functional impairments in schizophrenia. Previous work has highlighted the importance of motivational deficits more broadly, although no study has yet explored the unique effects of boredom on community outcomes. AIMS: This study aims to measure boredom proneness among outpatients diagnosed with schizophrenia to determine whether it is elevated in this population and to determine its relation to quality-of-life outcomes. METHODS: A self-report measure of boredom proneness along with standard measures of symptoms and functional status was administered to a community-dwelling sample of schizophrenia outpatients. RESULTS: Boredom proneness was found to be elevated in this population and was associated with reduced quality of life, specifically with leisure activity dissatisfaction and reduced sense of financial well-being. Negative symptoms were determined to be associated with reduced work and school functioning. CONCLUSION: This pattern of unique effects on quality of life highlights the clinical relevance of identifying a subjective state of boredom and has theoretical importance in distinguishing boredom proneness specifically from more general avolitional and amotivational conditions that have tended to be the focus of clinical observation and previous research.

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.