Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis.

Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity.

Randomized controlled trial of the glycine transporter 1 inhibitor PF-03463275 to enhance cognitive training and neuroplasticity in schizophrenia.

N-methyl-d-aspartate glutamate receptor (NMDAR) hypofunction is implicated in the impaired neuroplasticity and cognitive impairments associated with schizophrenia (CIAS). We hypothesized that enhancing NMDAR function by inhibiting the glycine transporter-1 (GLYT1) would improve neuroplasticity and thereby augment benefits of non-pharmacological cognitive training (CT) strategies. This study examined whether co-administration of a GLYT1 inhibitor and computerized CT would have synergistic effects on CIAS.

Auditory N100 amplitude deficits predict conversion to psychosis in the North American Prodrome Longitudinal Study (NAPLS-2) cohort.

Background: The auditory N100 is an event related potential (ERP) that is reduced in schizophrenia, but its status in individuals at clinical high risk for psychosis (CHR) and its ability to predict conversion to psychosis remains unclear. We examined whether N100 amplitudes are reduced in CHR subjects relative to healthy controls (HC), and this reduction predicts conversion to psychosis in CHR.

Methods: Subjects included CHR individuals (n = 552) and demographically similar HC subjects (n = 236) from the North American Prodrome Longitudinal Study.

Mismatch Negativity in Response to Auditory Deviance and Risk for Future Psychosis in Youth at Clinical High Risk for Psychosis.

Importance: Although clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P).

Objective: To examine whether mismatch negativity (MMN) event-related potential amplitude, which is deficient in schizophrenia, is reduced in young people with the CHR-P syndrome and associated with outcomes, accounting for effects of antipsychotic medication use.

One-Month Stability of Cyberball Post-Exclusion Ostracism Distress in Adolescents.

We examined one-month reliability, internal consistency, and validity of ostracism distress (Need Threat Scale) to simulated social exclusion during Cyberball. Thirty adolescents (13-18 yrs.) completed the Cyberball task, ostracism distress ratings, and measures of related clinical symptoms, repeated over one month.

Cognitive remediation for schizophrenia: An expert working group white paper on core techniques.

Cognitive remediation is now widely recognized as an effective treatment for cognitive deficits in schizophrenia. Its effects are meaningful, durable, and related to improvements in everyday functional outcomes. As with many therapies, the evolution of cognitive remediation has resulted in treatment programs that use a variety of specific techniques, yet share common core principles.

Association Between P300 Responses to Auditory Oddball Stimuli and Clinical Outcomes in the Psychosis Risk Syndrome.

Importance: In most patients, a prodromal period precedes the onset of schizophrenia. Although clinical criteria for identifying the psychosis risk syndrome (PRS) show promising predictive validity, assessment of neurophysiologic abnormalities in at-risk individuals may improve clinical prediction and clarify the pathogenesis of schizophrenia.

Objective: To determine whether P300 event-related potential amplitude, which is deficient in schizophrenia, is reduced in the PRS and associated with clinical outcomes.

Neurocognitive and Metacognitive Profiles of Intact Social Cognition in Prolonged Schizophrenia.

Social cognition (SC) appears to contribute to long-term outcomes in schizophrenia; however, little is known about whether different forms of SC are supported by the same cognitive processes. Accordingly, we examined the relationship of two domains of SC: emotion recognition (ER), using the Bell-Lysaker Emotion Recognition Test, and social inference (SI), using the Social Attribution Task-Multiple Choice, to measures of neurocognition, metacognition, theory of mind (ToM), and symptoms. Participants were 72 adults with schizophrenia in a nonacute phase.

Age-related trajectories of social cognition in youth at clinical high risk for psychosis: An exploratory study.

Background: Clinical high risk (CHR) status is characterized by impairments in social cognition, but questions remain concerning their stability over development. In cross-sectional analysis of a large naturalistic sample, the current study examined whether those at CHR status show deviant trajectories for age-related change in social cognitive ability, and whether these trajectories are influenced by treatment history.

Method: Emotion perception (EP) and theory of mind (ToM) were assessed in 675 CHR and 263 healthy comparison (HC) participants aged 12-35.

The Social Attribution Task - Multiple Choice (SAT-MC): Psychometric comparison with social cognitive measures for schizophrenia research.

The Social Attribution Task-Multiple Choice (SAT-MC) tests the ability to extract social themes from viewed object motion. This form of animacy perception is thought to aid the development of social inference, but appears impaired in schizophrenia. The current study was undertaken to examine psychometric equivalence of two forms of the SAT-MC and to compare their performance against social cognitive tests recommended for schizophrenia research.

Comparison of focused cognitive training and portable "brain-games" on functional outcomes for vocational rehabilitation participants.

Cognitive remediation performed in a cognitive laboratory was compared with a sham control using portable brain games to study effects on vocational, neurocognitive, and functional outcomes for participants with psychotic disorders in vocational rehabilitation (VR). Seventy-seven participants (61% schizophrenia, 39% other psychosis) in transitional (45.5%) or supported employment (54.

Lack of Diagnostic Pluripotentiality in Patients at Clinical High Risk for Psychosis: Specificity of Comorbidity Persistence and Search for Pluripotential Subgroups.

More than 20 years after the clinical high risk syndrome for psychosis (CHR) was first articulated, it remains controversial whether the CHR syndrome predicts onset of psychosis with diagnostic specificity or predicts pluripotential diagnostic outcomes. Recently, analyses of observational studies, however, have suggested that the CHR syndrome is not pluripotential for emergent diagnostic outcomes. The present report conducted additional analyses in previously reported samples to determine (1) whether comorbid disorders were more likely to persist in CHR patients compared to a comparison group of patients who responded to CHR recruitment efforts but did not meet criteria, termed help-seeking comparison subjects (HSC); and (2) whether clinically defined pluripotential CHR subgroups could be identified.

Machine learning identification of EEG features predicting working memory performance in schizophrenia and healthy adults.

Background: With millisecond-level resolution, electroencephalographic (EEG) recording provides a sensitive tool to assay neural dynamics of human cognition. However, selection of EEG features used to answer experimental questions is typically determined . The utility of machine learning was investigated as a computational framework for extracting the most relevant features from EEG data empirically.

Role of learning potential in cognitive remediation: Construct and predictive validity.

Background: The construct, convergent, discriminant, and predictive validity of Learning Potential (LP) was evaluated in a trial of cognitive remediation for adults with schizophrenia-spectrum disorders. LP utilizes a dynamic assessment approach to prospectively estimate an individual's learning capacity if provided the opportunity for specific related learning.

Methods: LP was assessed in 75 participants at study entry, of whom 41 completed an eight-week cognitive remediation (CR) intervention, and 22 received treatment-as-usual (TAU).

The Social Attribution Task-Multiple Choice (SAT-MC): A Psychometric and Equivalence Study of an Alternate Form.

The Social Attribution Task-Multiple Choice (SAT-MC) uses a 64-second video of geometric shapes set in motion to portray themes of social relatedness and intentions. Considered a test of "Theory of Mind," the SAT-MC assesses implicit social attribution formation while reducing verbal and basic cognitive demands required of other common measures. We present a comparability analysis of the SAT-MC and the new SAT-MC-II, an alternate form created for repeat testing, in a university sample (n = 92).

Social cognitive deficits in schizophrenia and their relationship to clinical and functional status.

While research on social cognitive impairments in schizophrenia is quickly growing, relatively little is still known about the severity and correlates of these impairments. The few studies that have examined this issue suggest that social cognitive impairments may be positively related to psychiatric symptoms and negatively related to functioning. In the current analyses of 119 stable outpatients with schizophrenia spectrum diagnoses, we sought to further characterize the nature of social cognitive impairments in schizophrenia.

Diagnostic specificity of neurophysiological endophenotypes in schizophrenia and bipolar disorder.

Background: The utility of an endophenotype depends on its ability to reduce complex disorders into stable, genetically linked phenotypes. P50 and P300 event-related potential (ERP) measures are endophenotype candidates for schizophrenia; however, their abnormalities are broadly observed across neuropsychiatric disorders. This study examined the diagnostic efficiency of P50 and P300 in schizophrenia as compared with healthy and bipolar disorder samples.

Social cognitive impairments and negative symptoms in schizophrenia: are there subtypes with distinct functional correlates?

Social cognitive impairments and negative symptoms are core features of schizophrenia closely associated with impaired community functioning. However, little is known about whether these are independent dimensions of illness and if so, whether individuals with schizophrenia can be meaningfully classified based on these dimensions (SANS) and potentially differentially treated. Five social cognitive measures plus Scale for the Assessment of Negative Symptoms (SANS) and Positive and Negative Syndrome Scale (PANSS) scores in a sample of 77 outpatients produced 2 distinct factors--a social cognitive factor and a negative symptom factor.

Thought disorder severity in compromised, deteriorated, and preserved intellectual course of schizophrenia.

Intellectual impairments are commonly found in schizophrenia and may precede onset of illness. Thought disorder (TD), also a key characteristic, entailing bizarre and idiosyncratic speech may be associated with early intellectual impairments. Schizophrenia and schizoaffective patients (n = 149) were characterized as having preserved, deteriorated, or compromised intellect using premorbid and current IQ estimates.

Comparison of computational methods for the evaluation of learning potential in schizophrenia.

Learning potential (LP) refers to the ability to improve cognitive performance as a result of training. It is typically assessed by test-train-test administrations of a task, wherein changes in pre-post performance are an index of LP. In schizophrenia research, LP has been suggested as a mediator of the relationship between static neurocognition and functional outcome.

Functional significance of preserved affect recognition in schizophrenia.

Affect recognition (AR) is a core component of social information processing; thus, it may be critical to understanding social behavior and functioning in broader aspects of daily living. Deficits in AR are well documented in schizophrenia, but there is also evidence that many individuals with schizophrenia perform AR tasks at near-normal levels. In the current study, we sought to evaluate the functional significance of AR deficits in schizophrenia by comparing subgroups with normal-range and impaired AR performance on proxy and interviewer-rated measures of real-world functioning.

Memory profiles in schizophrenia: categorization validity and stability.

Background: Memory profiles corresponding to nearly normal (NN), Subcortical impairment (Sub) and Cortical impairment (Cort) have been identified in schizophrenia by several investigators using cluster analytic techniques. Specific aims of the current study were to (1) perform a K means cluster analysis using Hopkins Verbal Learning Test-R scores (2) create classification rules based upon cluster distributions and expected memory profiles and to determine their concordance with cluster analysis; (3) explore differences among classified groups on demographic, neurocognitive and social cognitive domains; and (4) determine the stability of the classifications 12 months later.

Methods: Clinical and neuropsychological assessments were obtained at intake and 12 months from 151 outpatients with schizophrenia or schizoaffective disorder from an urban community mental health center.

Event-related potential abnormalities in schizophrenia: a failure to "gate in" salient information?

Sensory gating refers to the central nervous system's ability to filter sensory inputs, and can be measured by comparing the suppression of event-related brain potential (ERP) amplitudes in a paired auditory stimulus procedure. Poor gating scores in schizophrenia may be caused by abnormal responses to the first (S1), the second (S2) or both of the paired stimuli. However, since S1 and S2 responses may index separate psychological phenomenon, corresponding to the ability to "gate in" and "gate out" sensory stimuli respectively, the precise mechanism affected in schizophrenia remains unclear.

Secretin effects on cerebellar-dependent motor learning in schizophrenia.

Objective: Pervasive cognitive deficits in schizophrenia are a major cause of disability among individuals with the disorder. One such deficit is the loss of effective associative learning, which is readily assessed via eye-blink conditioning procedures. The authors examined the efficacy of secretin, a hormonal agonist for the prototype group B G-protein-coupled receptors, in ameliorating eye-blink conditioning deficits in schizophrenia patients.