Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome.

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

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. Stable outpatients with schizophrenia participated in this double-blind, placebo-controlled, within-subject, crossover augmentation study. Participants received placebo or GLYT1 inhibitor (PF-03463275) for two 5-week periods separated by 2 weeks of washout. PF-03463275 doses (40 or 60 mg twice daily) were selected to produce high GLYT1 occupancy. To limit pharmacodynamic variability, only cytochrome P450 2D6 extensive metabolizers were included. Medication adherence was confirmed daily. Participants received 4 weeks of CT in each treatment period. Cognitive performance (MATRICS Consensus Cognitive Battery) and psychotic symptoms (Positive and Negative Syndrome Scale) were assessed in each period. 71 participants were randomized. PF-03463275 in combination with CT was feasible, safe, and well-tolerated at the doses prescribed but did not produce greater improvement in CIAS compared to CT alone. PF-03463275 was not associated with improved CT learning parameters. Participation in CT was associated with improvement in MCCB scores.

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. Follow-up assessments identified CHR individuals who converted to psychosis (CHRC; n = 73) and those who did not (CHR-NC; n = 225) over 24 months. Electroencephalography data were collected during an auditory oddball task containing Standard, Novel, and Target stimuli. N100 peak amplitudes following each stimulus were measured at electrodes Cz and Fz. RESULTS: The CHR subjects had smaller N100 absolute amplitudes than HC subjects at Fz (F(1,786) = 4.00, p 0.046). A model comparing three groups (CHRC, CHR-NC, HC) was significant for Group at the Cz electrode (F(2,531) = 3.58, p = 0.029). Both Standard (p = 0.019) and Novel (p = 0.017) stimuli showed N100 absolute amplitude reductions in CHR-C relative to HC. A smaller N100 amplitude at Cz predicted conversion to psychosis in the CHR cohort (Standard: p = 0.009; Novel: p = 0.001) and predicted shorter time to conversion (Standard: p = 0.013; Novel: p = 0.001). CONCLUSION: N100 amplitudes are reduced in CHR individuals which precedes the onset of psychosis. N100 deficits in CHR individuals predict a greater likelihood of conversion to psychosis. Our results highlight N100's utility as a biomarker of psychosis risk.

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. Design, Setting, and Participants: MMN data were collected as part of the multisite case-control North American Prodrome Longitudinal Study (NAPLS-2) from 8 university-based outpatient research programs. Baseline MMN data were collected from June 2009 through April 2013. Clinical outcomes were assessed throughout 24 months. Participants were individuals with the CHR-P syndrome and healthy controls with MMN data. Participants with the CHR-P syndrome who developed psychosis (ie, converters) were compared with those who did not develop psychosis (ie, nonconverters) who were followed up for 24 months. Analysis took place between December 2019 and December 2021. Main Outcomes and Measures: Electroencephalography was recorded during a passive auditory oddball paradigm. MMN elicited by duration-, pitch-, and duration + pitch double-deviant tones was measured. Results: The CHR-P group (n = 580; mean [SD] age, 19.24 [4.39] years) included 247 female individuals (42.6%) and the healthy control group (n = 241; mean age, 20.33 [4.74] years) included 114 female individuals (47.3%). In the CHR-P group, 450 (77.6%) were not taking antipsychotic medication at baseline. Baseline MMN amplitudes, irrespective of deviant type, were deficient in future CHR-P converters to psychosis (n = 77, unmedicated n = 54) compared with nonconverters (n = 238, unmedicated n = 190) in both the full sample (d = 0.27) and the unmedicated subsample (d = 0.33). In the full sample, baseline medication status interacted with group and deviant type indicating that double-deviant MMN, compared with single deviants, was reduced in unmedicated converters compared with nonconverters (d = 0.43). Further, within the unmedicated subsample, deficits in double-deviant MMN were most strongly associated with earlier conversion to psychosis (hazard ratio, 1.40 [95% CI, 1.03-1.90]; P = .03], which persisted over and above positive symptom severity. Conclusions and Relevance: This study found that MMN amplitude deficits were sensitive to future psychosis conversion among individuals at risk of CHR-P, particularly those not taking antipsychotic medication at baseline, although associations were modest. While MMN shows limited promise as a biomarker of psychosis onset on its own, it may contribute novel risk information to multivariate prediction algorithms and serve as a translational neurophysiological target for novel treatment development in a subgroup of at-risk individuals.

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. This paper is the product of a cognitive remediation expert working group consensus meeting to identify core features of the treatment and produce recommendations for its design, conduct, reporting, and implementation. Four techniques were identified as core features of cognitive remediation: facilitation by a therapist, cognitive exercise, procedures to develop problem-solving strategies, and procedures to facilitate transfer to real world functioning. Treatment techniques within each of these core features are presented to facilitate decisions for clinical trials and implementation in clinical settings.

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. Design, Setting, and Participants: Auditory P300 data were collected as part of the multisite, case-control North American Prodrome Longitudinal Study (NAPLS-2) at 8 university-based outpatient programs. Participants included 552 individuals meeting PRS criteria and 236 healthy controls with P300 data. Auditory P300 data of participants at risk who converted to psychosis (n = 73) were compared with those of nonconverters who were followed up for 24 months and continued to be symptomatic (n = 135) or remitted from the PRS (n = 90). Data were collected from May 27, 2009, to September 17, 2014, and were analyzed from December 3, 2015, to May 1, 2019. Main Outcomes and Measures: Baseline electroencephalography was recorded during an auditory oddball task. Two P300 subcomponents were measured: P3b, elicited by infrequent target stimuli, and P3a, elicited by infrequent nontarget novel stimuli. Results: This study included 788 participants. The PRS group (n = 552) included 236 females (42.8%) (mean [SD] age, 19.21 [4.38] years), and the healthy control group (n = 236) included 111 females (47.0%) (mean [SD] age, 20.44 [4.73] years). Target P3b and novelty P3a amplitudes were reduced in at-risk individuals vs healthy controls (d = 0.37). Target P3b, but not novelty P3a, was significantly reduced in psychosis converters vs nonconverters (d = 0.26), and smaller target P3b amplitude was associated with a shorter time to psychosis onset in at-risk individuals (hazard ratio, 1.45; 95% CI, 1.04-2.00; P = .03). Participants with the PRS who remitted had baseline target P3b amplitudes that were similar to those of healthy controls and greater than those of converters (d = 0.51) and at-risk individuals who remained symptomatic (d = 0.41). Conclusions and Relevance: In this study, deficits in P300 amplitude appeared to precede psychosis onset. Target P3b amplitudes, in particular, may be sensitive to clinical outcomes in the PRS, including both conversion to psychosis and clinical remission. Auditory target P3b amplitude shows promise as a putative prognostic biomarker of clinical outcome in the PRS.

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. Need Threat Scale ratings of ostracism distress showed adequate test-retest reliability and internal consistency at both occasions. Construct validity was demonstrated via relationships with closely related constructs of anxiety, anxiety sensitivity, and emotion dysregulation, and weaker associations with more distal constructs of state paranoia and subclinical psychosis-like experiences. While ratings of ostracism distress and anxiety were significantly attenuated at retest, most participants continued to experience post-Cyberball ostracism distress at one-month follow-up, which indicates that the social exclusion induction of Cyberball persisted despite participants' familiarity with the paradigm. Overall, results suggest that the primary construct of ostracism distress is preserved over repeated administration of Cyberball, with reliability sufficient for usage in longitudinal research. These findings have important implications for translating this laboratory simulation of social distress into developmental and clinical intervention studies.

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. Multivariate analysis of variance and univariate analysis of variance revealed participants with intact ER had better neurocognition (MATRICS Consensus Cognitive Battery [MCCB]), metacognition (Metacognition Assessment Scale-Abbreviated), ToM (The Hinting Task), and higher emotional discomfort symptoms than participants with impaired scores. Participants with intact SI had higher MCCB visual and verbal learning and SC scores. Stepwise regressions revealed neurocognition and metacognition uniquely contribute to ER performance. Results suggest ER and SI are differentially related to cognitive processes.

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. Age effects in CHR were modeled against HC age-expected performance. Prior medication status was tested for interactions with age. RESULTS: CHR exhibited normal age trajectory for EP, but significantly lower slopes for ToM from age 17 onward. This effect was specific to stimuli exhibiting sarcasm and not to detection of lies. When treatment history was included in the model, age-trajectory appeared normal in CHR subjects previously prescribed both antipsychotics and antidepressant medication, although the blunted trajectory still characterized 80% of the sample. DISCUSSION: Cross-sectional analyses suggested that blunting of ToM in CHR develops in adolescence, while EP abilities were diminished evenly across the age range. Exploratory analyses of treatment history suggested that ToM was not affected, however, in CHRs with lifetime histories of both antipsychotic and antidepressant medications. Reduction in age-expected ToM ability may impair the ability of individuals at CHR to meet social developmental challenges in adolescence. Medication effects on social cognition deserve further study.

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. Thirty-two schizophrenia (SZ) and 30 substance use disorder (SUD) participants completed both SAT-MC forms, the Bell-Lysaker Emotion Recognition Task (BLERT), Hinting Task, The Awareness of Social Inference Test (TASIT), Ambiguous Intentions and Hostility Questionnaire (AIHQ) and questionnaire measures of interpersonal function. Test sensitivity, construct and external validity, test-retest reliability, and internal consistency were evaluated. SZ scored significantly lower than SUD on both SAT-MC forms, each classifying ~60% of SZ as impaired, compared with ~30% of SUD. SAT-MC forms demonstrated good test-retest and parallel form reliability, minimal practice effect, high internal consistency, and similar patterns of correlation with social cognitive and external validity measures. The SAT-MC compared favorably to recommended social cognitive tests across psychometric features and, with exception of TASIT, was most sensitive to impairment in schizophrenia when compared to a chronic substance use sample.

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 (54.5%) were randomly assigned to 6 months of portable cognitive-games (CG) or cognitive remediation (CR) plus a weekly goal-setting group, and evaluated during training, post-training and at 12 months. Overall rates of employment did not differ significantly at 12-month follow-up; however, VR + CG attained employment more rapidly during training. A significant time by condition interaction favored VR + CR on Quality of Life Total Score and Instrumental Functioning over 12 months. Neurocognitive outcomes favored VR + CR, particularly on attention. Training hours related significantly to neurocognitive improvement regardless of condition. No differences were found in training adherence despite portability for VR + CG. Results indicate that VR + CR had significantly greater effect than VR + CG on neurocognition and community functioning, but not on employment outcome. Job attainment rates during the training period revealed a potential advantage for portable training raising new questions concerning how cognitive remediation can be most effectively integrated with VR.

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. All data were derived from 2 multisite studies in which DSM-IV structured diagnostic interviews were conducted at baseline and at 6-month intervals. Across samples we observed persistence of any nonpsychotic disorder in 80/147 CHR cases (54.4%) and in 48/84 HSC cases (57.1%, n.s.). Findings with persistence of anxiety, depressive, and bipolar disorders considered separately were similar. Efforts to discover pluripotential CHR subgroups were unsuccessful. These findings add additional support to the view that the CHR syndrome is not pluripotential for predicting various diagnostic outcomes but rather is specific for predicting emergent psychosis.

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 a priori. The utility of machine learning was investigated as a computational framework for extracting the most relevant features from EEG data empirically. METHODS: Schizophrenia (SZ; n = 40) and healthy community (HC; n = 12) subjects completed a Sternberg Working Memory Task (SWMT) during EEG recording. EEG was analyzed to extract 5 frequency components (theta1, theta2, alpha, beta, gamma) at 4 processing stages (baseline, encoding, retention, retrieval) and 3 scalp sites (frontal-Fz, central-Cz, occipital-Oz) separately for correctly and incorrectly answered trials. The 1-norm support vector machine (SVM) method was used to build EEG classifiers of SWMT trial accuracy (correct vs. incorrect; Model 1) and diagnosis (HC vs. SZ; Model 2). External validity of SVM models was examined in relation to neuropsychological test performance and diagnostic classification using conventional regression-based analyses. RESULTS: SWMT performance was significantly reduced in SZ (p < .001). Model 1 correctly classified trial accuracy at 84 % in HC, and at 74 % when cross-validated in SZ data. Frontal gamma at encoding and central theta at retention provided highest weightings, accounting for 76 % of variance in SWMT scores and 42 % variance in neuropsychological test performance across samples. Model 2 identified frontal theta at baseline and frontal alpha during retrieval as primary classifiers of diagnosis, providing 87 % classification accuracy as a discriminant function. CONCLUSIONS: EEG features derived by SVM are consistent with literature reports of gamma's role in memory encoding, engagement of theta during memory retention, and elevated resting low-frequency activity in schizophrenia. Tests of model performance and cross-validation support the stability and generalizability of results, and utility of SVM as an analytic approach for EEG feature selection.

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). LP was assessed in a "test-train-test" verbal learning paradigm. Incremental predictive validity was assessed as the degree to which LP predicted memory skill acquisition above and beyond prediction by static verbal learning ability. RESULTS: Examination of construct validity confirmed that LP scores reflected use of trained semantic clustering strategy. LP scores correlated with executive functioning and education history, but not other demographics or symptom severity. Following the eight-week active phase, TAU evidenced little substantial change in skill acquisition outcomes, which related to static baseline verbal learning ability but not LP. For the CR group, LP significantly predicted skill acquisition in domains of verbal and visuospatial memory, but not auditory working memory. Furthermore, LP predicted skill acquisition incrementally beyond relevant background characteristics, symptoms, and neurocognitive abilities. CONCLUSIONS: Results suggest that LP assessment can significantly improve prediction of specific skill acquisition with cognitive training, particularly for the domain assessed, and thereby may prove useful in individualization of treatment.

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). Score distributions and patterns of association with external validation measures were nearly identical between the two forms, with convergent and discriminant validity supported by association with affect recognition ability and lack of association with basic visual reasoning. Internal consistency of the SAT-MC-II was superior (alpha = .81) to the SAT-MC (alpha = .56). Results support the use of SAT-MC and new SAT-MC-II as equivalent test forms. Demonstrating relatively higher association to social cognitive than basic cognitive abilities, the SAT-MC may provide enhanced sensitivity as an outcome measure of social cognitive intervention trials.

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. Supplemental ERP measures and a multivariate classification approach were evaluated as methods to improve specificity. METHODS: Diagnostic classification was first modeled in schizophrenia (SZ = 50) and healthy normal (HN = 50) samples using hierarchical logistic regression with predictors blocked by 4 levels of analysis: (1) P50 suppression, P300 amplitude, and P300 latency; (2) N100 amplitude; (3) evoked spectral power; and (4) P50 and P300 hemispheric asymmetry. The optimal model was cross-validated in a holdout sample (SZ = 34, HN = 31) and tested against a bipolar (BP = 50) sample. RESULTS: P50 and P300 endophenotypes classified SZ from HN with 71% accuracy (sensitivity = .70, specificity = .72) but did not differentiate SZ from BP above chance level. N100 and spectral power measures improved classification accuracy of SZ vs HN to 79% (sensitivity = .78, specificity = .80) and SZ vs BP to 72% (sensitivity = .74, specificity = .70). Cross validation analyses supported the stability of these models. CONCLUSIONS: Although traditional P50 and P300 measures failed to differentiate schizophrenia from bipolar participants, N100 and evoked spectral power measures added unique variance to classification models and improved accuracy to nearly the same level achieved in comparison of schizophrenia to healthy individuals.

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. Specifically, we examined (1) social cognitive impairments on four different social cognitive tasks including measures of emotional processing and Theory of Mind and (2) the demographic, symptom and functional correlates of these impairments. For three of the four social cognitive tasks examined, the majority of participants performed 1 or more S.D. worse than healthy controls, with variability in the degree of impairment across tasks. Contrary to expectation, correlations between social cognitive performance on each of the four tasks and clinical and functional features were few and weak, and for the most part did not replicate the previously reported relationship of social cognition to severity of symptoms or current functional status.

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. Factor scores were used in a cluster analysis, which yielded 3 well-defined groupings--a high negative symptom group (HN) and 2 low negative symptom groups, 1 with higher social cognition (HSC) and 1 with low social cognition (LSC). To make these findings more practicable for research and clinical settings, a rule of thumb for categorizing using only the Mayer-Salovey-Caruso Emotional Intelligence Test and PANSS negative component was created and produced 84.4% agreement with the original cluster groups. An additional 63 subjects were added to cross validate the rule of thumb. When samples were combined (N = 140), the HSC group had significantly better quality of life and Global Assessment of Functioning (GAF) scores, higher rates of marriage and more hospitalizations. The LSC group had worse criminal and substance abuse histories. With 2 common assessment instruments, people with schizophrenia can be classified into 3 subgroups that have different barriers to community integration and could potentially benefit from different treatments.

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. TD and severity of cognitive symptom were ascertained using the Gorham's Proverbs Test, PANSS and SAPS. Significant relations were found between performance-based (Gorham's Bizarreness score) and clinically-rated PANSS (r = 0.51) and SAPS (r = 0.50) symptomatology. Group contrasts on bizarreness revealed higher severity TD (p < 0.01) in compromised as compared with deteriorated and preserved groups. Groups did not differ significantly on PANSS and SAPS related TD ratings. Findings support the etiological significance of TD with respect to clinical course. Importantly, groups were distinguished by performance-based but not on clinical ratings of TD, suggesting a more reliable, trait-related, index of mental change relevant to the course of schizophrenia.

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. While a number of studies do indicate that LP assessment improves prediction of functioning beyond standard administrations of the same task, multiple approaches of computing LP indices have been used in this work. Multiple psychometric issues have been raised with respect to computation of change scores, but have not been widely recognized in LP assessment. To address this issue, the current study aimed to evaluate the test-retest reliability, interrelatedness, construct, and criterion validity of several conventional indices of LP, obtained from a test-train-test version of a list-learning task administered to 43 individuals with chronic schizophrenia. Overall, test-retest and intercorrelation coefficients indicated variable reliability and convergence across methods. While LP indices generally correlated more highly with independent measures of neurocognition and community functioning than pretraining list learning scores, coefficients were comparably small. Recommendations and measurement issues inherent to the LP construct are discussed.