Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents.     

Neurocognitive profile in adolescents with early-onset schizophrenia: clinical correlates.

BACKGROUND: Neurocognitive impairments have been documented in adolescents with early-onset schizophrenia (EOS; onset by age 18) and are important treatment targets. Information concerning the severity, pattern, and clinical correlates of these deficits in EOS remains limited. METHODS: Tests assessing motor skills, attention, memory, visuospatial abilities and executive functioning were administered to 54 clinically stabilized adolescents with EOS and 52 age- and sex-matched healthy controls. Childhood-onset patients (onset by age 13) were compared to those with an adolescent onset of illness. Patients' neurocognitive profiles were compared to those of controls. Relationships between neurocognitive deficits and demographic and clinical characteristics were explored. RESULTS: Neurocognitive profiles did not differ between childhood- and adolescent-onset participants. Patients showed a generalized neurocognitive deficit of 2.0 SDs compared to controls, with relative deficit in executive functioning and relative sparing of language and visuospatial abilities. Degree of generalized neurocognitive impairment was associated with premorbid adjustment and negative symptom severity (Adjusted R(2) = .39). CONCLUSIONS: Results document both a significant generalized deficit and a relative deficit of executive functioning in adolescents with EOS. The overall pattern is similar to that observed in severely ill first-episode adult patients. The impairments across multiple neurocognitive domains suggest widespread brain dysfunction in EOS.     

Cognitive Factor Structure and Invariance in People With Schizophrenia,Their Unaffected Siblings,and Controls

Introduction: Separable, but positively correlated, factors emerge from analyses of cognitive test data in schizophrenia and control samples (eg, verbal memory and processing speed) and these factors guide data reduction. Additionally, data support a hierarchical model of cognitive performance, in which these correlations reflect the influence of a higher-order factor, referred to as “g.” We tested these findings in large, carefully screened samples of people with schizophrenia (n = 496), their unaffected siblings (n = 504), and controls (n = 823). Furthermore, we tested the hypothesis that cognitive performance in schizophrenia is more generalized across domains than among siblings and controls. Method: A combination of exploratory and confirmatory factor analyses (EFA and CFA) and multiple groups CFA (MCFA) was used. Results: EFA yielded factors for verbal memory, visual memory, processing speed, working memory span, nback performance, and card sorting. The solution was consistent across groups, in terms of the factor assignments of individual cognitive variables and the magnitude of loadings. Method variance may have contributed to the card sorting, visual memory, and nback factors. CFA indicated that the hierarchical model, incorporating a “g” factor, was a good fit for data from all groups. MCFA suggested that this hierarchical structure was fully invariant for controls and siblings. While the variable/factor loadings for the schizophrenia group also were invariant with comparison groups, factor/“g” loadings were higher in schizophrenia, as were correlations among factor-based composite scores. Conclusions: Cognitive variables sort into domains consistently in schizophrenia, unaffected siblings, and controls. However, performance in schizophrenia is more generalized and less domain specific.     

Neurocognition in the Extended Psychosis Phenotype: Performance of a Community Sample of Adolescents With Psychotic Symptoms on the MATRICS Neurocognitive Battery

Neurocognitive dysfunction is well established in psychosis, but recent work suggests that processing speed deficits might represent a particularly important cognitive deficit. A number of significant confounds, however, such as disease chronicity and antipsychotic medication use, have been shown to affect processing speed, causing debate as to the core cognitive features of psychosis. We adopted a novel strategy of testing neurocognitive performance in the “extended psychosis phenotype,” involving community-based adolescents who are not clinically psychotic but who report psychotic symptoms and who are at increased risk of psychosis in adulthood. This allows investigation of the earliest cognitive factors associated with psychosis risk, while excluding potential confounds such as disease chronicity and antipsychotic use. A population sample of 212 school-going adolescents aged 11–13 years took part in this study. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Neurocognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus neurocognitive battery. Adolescents with psychotic symptoms performed significantly more poorly on 3 processing speed tasks: Trail Making Test-A (F = 3.3, P < .05), Trail Making Test-B (F = 3.1, P < .05), and digit symbol coding task (F = 7.0, P < .001)—as well as on a nonverbal working memory (spatial span) task (F = 3.2, P < .05). Our findings support the idea that neurocognitive impairment, and processing speed impairment in particular, is a core feature of psychosis risk. This group likely demonstrates some of the earliest cognitive impairments associated with psychosis vulnerability.Key words: epidemiology/adolescents/cognitionKey words: epidemiology, adolescents, cognition     

Has the Generalized Deficit Become the Generalized Criticism?

The “generalized cognitive deficit problem” refers to a situation in which a generalized deficit gives the false appearance of a specific deficit due to the psychometric properties of tests, and it is an important methodological consideration in schizophrenia research. However, it also generates considerable confusion and is often used indiscriminately as a scientific criticism, even in situations to which it does not apply. Further, the generalized deficit problem creates few concerns in interpretation for many central questions in contemporary schizophrenia research. The research literature has shifted away from the traditional goal of identifying generalized vs differential deficits, and the field now demonstrates (1) increased recognition that a generalized deficit, broadly defined, probably does not exist in schizophrenia, (2) increased emphasis on explaining both shared and unique variance across measures to understand the mechanisms through which cognition relates to external variables (eg, functional outcome), and (3) increased use of neuroscientific methods to explore cognition in schizophrenia in which the structure and richness of data can be used to minimize misinterpretation of the sort that can occur when using only behavioral measures. Clearly, consideration of the generalized deficit still remains essential in certain experimental contexts, but criticisms based on this concern are unwarranted in many other situations in schizophrenia research. This commentary is intended to help clarify the distinctions between these 2 situations so that concerns will be expressed in a more selective, less reflexive, manner.The generalized deficit in schizophrenia research has become a confound in all senses of the word. On the one hand, it is a well-recognized methodological challenge that has produced spirited debate. On the other hand, this long-standing issue has generated confusion through its indiscriminant use as a criticism, both in situations to which it applies and in situations to which it does not.The “generalized deficit” in schizophrenia refers to the tendency for patients to perform poorly relative to controls across a range of cognitive tasks. The “generalized deficit problem” occurs when the generalized deficit gives the false appearance of a specific deficit (ie, a differential deficit) due to the psychometric properties of the tests used. Although the topic of generalized vs differential deficits in schizophrenia has nearly disappeared from the research literature (see below), it is alive and well in the reviews of papers and grants. This commentary attempts to help discriminate between situations in which concerns about the generalized deficit are appropriate and warranted, and those in which the generalized deficit creates few, if any, concerns.     

Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far?

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website “www.clinicaltrials.gov” using the terms “schizophrenia AND cognition,” “schizophrenia AND neurocognition,” “schizophrenia AND neurocognitive tests,” “schizophrenia AND MATRICS,” “schizophrenia AND MCCB,” “schizophrenia AND BACS,” “schizophrenia AND COGSTATE,” and “schizophrenia AND CANTAB” and “first-episode schizophrenia AND cognition.” The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia.     

Elevated Antisaccade Error Rate as an Intermediate Phenotype for Psychosis Across Diagnostic Categories

Background: Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit. Methods: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery. Results: Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives’ deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands. Conclusions: These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.Key words: schizophrenia, schizoaffective disorder, bipolar disorder, endophenotype, family study     

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.     

Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder.

OBJECTIVE: Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD). This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments. METHOD: The performance of 19 adolescents with schizophrenia, 20 adolescents with ADHD, and 30 normal adolescents on a broad battery of cognitive tests was compared. RESULTS: The schizophrenic group showed the most pronounced deficits on tests of abstraction, visual memory, and motor function in comparison with the subjects with ADHD, while the ADHD subjects had the most pronounced deficits on measures of attention, verbal memory, and learning. CONCLUSIONS: The subjects with schizophrenia appeared to have a more general pattern of brain dysfunction, whereas the impairment of the ADHD subjects seemed to be relatively specific to tests associated with frontal lobe function.     

The Impact of Aerobic Exercise on Brain-Derived Neurotrophic Factor and Neurocognition in Individuals With Schizophrenia: A Single-Blind,Randomized Clinical Trial

Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits. Yet, findings from studies of animals, clinical and nonclinical populations have linked neurocognitive improvements to increases in aerobic fitness (AF) via aerobic exercise training (AE). Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor (BDNF). However, the impact of AE on neurocognition, and the putative role of BDNF, have not been investigated in schizophrenia. Employing a proof-of-concept, single-blind, randomized clinical trial design, 33 individuals with schizophrenia were randomized to receive standard psychiatric treatment (n = 17; “treatment as usual”; TAU) or attend a 12-week AE program (n = 16) utilizing active-play video games (Xbox 360 Kinect) and traditional AE equipment. Participants completed assessments of AF (indexed by VO₂ peak ml/kg/min), neurocognition (MATRICS Consensus Cognitive Battery), and serum-BDNF before and after and 12-week period. Twenty-six participants (79%) completed the study. At follow-up, the AE participants improved their AF by 18.0% vs a −0.5% decline in the TAU group (P = .002) and improved their neurocognition by 15.1% vs −2.0% decline in the TAU group (P = .031). Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4% and 14.6% of the neurocognitive improvement variance, respectively. The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population. Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe, nonstigmatizing, and side-effect-free intervention.Key words: aerobic fitness, cognition, neurotrophins, brain-derived neurotrophic factor/active-play video games     

Shared intermediate phenotypes for schizophrenia and bipolar disorder: neuroanatomical features of subtypes distinguished by executive dysfunction

Background

Shared genetic vulnerability for schizophrenia and bipolar disorder may be associated with common neuroanatomical features. In view of the evidence for working memory dysfunction as a candidate intermediate phenotype for both disorders, we explored neuroanatomical distinctions between subtypes defined according to working memory (n-back task) performance.

Methods

We analyzed T₁-weighted MRI scans for patients with schizophrenia-spectrum disorder, bipolar-I disorder (BD-I) and healthy controls. The VBM8 toolbox was used to assess differences in grey and white matter volume across traditional diagnostic groups (schizophrenia v. BD-I). Subsequently, groups were defined as “executively spared” (ES) based on the achievement of greater than 50% accuracy in the 2-back task performance (comparable to performance in the control group) or “executively deficit” (ED) based on the achievement of less than 50% accuracy.

Results

Our study included 40 patients with schizophrenia-spectrum disorders, 30 patients with BD-I and 34 controls. Both the schizophrenia and BD-I groups showed grey matter volume reductions relative to the control group, but not relative to each other. The ED subtype (n = 32 [10 BD-I, 22 schizophrenia]) showed grey matter volume reductions in the bilateral superior and medial frontal gyri, right inferior opercular gyri and hippocampus relative to controls. The ES subtype (n = 38 [20 BD-I, 18 schizophrenia]) showed grey matter volume reductions in the right precuneus and left superior and medial orbital frontal gyri relative to controls. The ED subtype showed grey matter volume reduction in the right inferior frontal and precentral gyri relative to the ES subtype. There were no significant differences in white matter volume in any group comparisons.

Limitations

This analysis was limited by small sample sizes. Further, insufficient numbers were available to assess a control-deficit comparison group. We were unable to assess the effects of mood stabilizer dose on brain structure.

Conclusion

Neuroanatomical commonalities are evident among patients with schizophrenia-spectrum disorders and BD-I with working memory deficits. Reduced inferior frontal lobe volume may mediate cognitive deficits shared across the psychosis–mood spectrum.     

Anatomical Distance Affects Functional Connectivity in Patients With Schizophrenia and Their Siblings

Background: The efficiency of human brain depends on the integrity of both long- and short-range connections, but the long-range connections need to be “penalized” to reduce overall wiring costs. This principle, termed as the anatomical distance function (ADF), refers to the presence of an inverse relationship between anatomical distance and connectivity. A crucial developmental feature that occurs in normal adolescence is the weakening of ADF, which is characterized by a selective strengthening of long-distance connections. Schizophrenia is associated with widespread dysconnectivity that is linked to aberrant cortical development. Methods: We studied the ADF in adults with schizophrenia (n = 28), their age-matched siblings (n = 28), and healthy controls (n = 60). We investigated the proportional abnormalities in the long-range connections involving interhemispheric, subcortical, frontal, and salience network regions and localized the connections showing most significant changes in schizophrenia. The groups were discriminated on the basis of short- and long-range connectivity using a machine-learning algorithm. Results: Both patients and their siblings showed abnormally pronounced ADF. This was associated with a disproportionate reduction in the number of long-range connections, affecting the subcortical, interhemispheric, and the salience network connections. The abnormalities in long-range connections had superior ability to accurately identify group membership. Conclusions: A crucial organizing principle of the brain architecture that becomes apparent during normal adolescence is disturbed in schizophrenia. While siblings show some evidence of compensating for this deficit, patients lack putative compensatory changes. Age-related shift in ADF provides an explanatory framework for the developmental emergence of widespread dysconnectivity that is influenced by genetic risk in schizophrenia.Key words: anatomical distance, schizophrenia, genetic risk, functional connectivity, wiring cost, salience network     

Assessment of Trait and State Aspects of Depression in Schizophrenia

Depression and negative symptoms can be difficult to distinguish in schizophrenia. Assessments for negative symptoms usually account for the longitudinal nature of these symptoms, whereas instruments available to measure depression mainly assess current or recent symptoms. This construct difference may confound comparison of depressive and negative symptoms in schizophrenia because both domains may have trait-like aspects. We developed an instrument to measure both longitudinal “trait” as well as recent “state” symptoms of depression and tested this instrument (Maryland Trait and State Depression [MTSD] scale) in a sample of 98 individuals with schizophrenia or schizoaffective disorder and 115 community participants without psychotic illness. Exploratory factor analysis of the MTSD revealed 2 factors accounting for 73.4% of the variance; these 2 factors corresponded with “trait” and “state” depression inventory items. Neither MTSD-state nor MTSD-trait was correlated with negative symptoms as measured with the Brief Negative Symptom Scale (r = .07 and −.06, respectively) in schizophrenia patients. MTSD state and trait scores were significantly correlated with the Brief Psychiatric Rating Scale depression subscale (r = .58 and .53, respectively) as well as the Profile of Mood States depression subscale (r = .57 and .44). Persons with schizophrenia had significantly greater trait depressive symptoms than controls (P = .031). Individuals with schizoaffective disorder had significantly higher trait depression (P = .001), but not state depression (P = .146), compared with schizophrenia patients. Trait depressive symptoms are prominent in schizophrenia and are distinct from negative symptoms.Key words: BNSS, schizoaffective disorder, symptom domain     

Neuroplasticity-Based Cognitive Training in Schizophrenia: An Interim Report on the Effects 6 Months Later

Background: New cognitive treatments for schizophrenia are needed that drive persistent gains in cognition and functioning. Using an innovative neuroplasticity-based cognitive training approach, we report our interim findings on the effects on cognition and functional outcome at 6 months after treatment. Methods: Thirty-two clinically stable schizophrenia subjects were randomly assigned to either targeted cognitive training (TCT, N = 22) or a computer games (CGs) control condition (N = 10). Twelve TCT subjects completed 50 hours of auditory based training; 10 TCT subjects completed an additional 50 hours of training targeting visual and cognitive control processes. Subjects were assessed on neurocognition and functional outcome after training and at 6-month follow-up. Results: Both TCT subject groups showed significant durable gains at 6 months on measures of verbal learning/memory and cognitive control. Only TCT subjects who completed 100 hours of training showed durable gains on processing speed and global cognition, with nonsignificant improvement in functional outcome. Improved cognition was significantly associated with improved functional outcome at 6 months for TCT subjects. Conclusions: A total of 50 hours of neuroplasticity-based computerized cognitive training appears sufficient to drive improvements in verbal learning/memory and cognitive control that endure 6 months beyond the intervention, but a higher “dose” and more “broad-spectrum” training may be necessary to drive enduring gains in processing speed and global cognition. Training-induced cognitive improvement is related to enhanced functioning at 6 months. These data suggest that (1) higher and “broader” doses of cognitive training may confer the most benefits for schizophrenia patients; (2) the posttraining period opens a critical window for aggressive adjunctive psychosocial rehabilitation.     

Working memory predicts presence of auditory verbal hallucinations in schizophrenia and bipolar disorder with psychosis

Objective: The recent dramatic increase in research investigating auditory verbal hallucinations (AVHs) has broadened the former narrow focus on schizophrenia to incorporate additional populations that experience these symptoms. However, an understanding of potential shared mechanisms remains elusive. Based on theories suggesting a failure of top-down cognitive control, we aimed to compare the relationship between AVHs and cognition in two categorical diagnoses of psychosis, schizophrenia and psychotic bipolar disorder. Method: A total of 124 adults aged 21–60 participated, of whom 76 had present-state psychosis (schizophrenia, n = 53; bipolar disorder with psychosis, n = 23), and 48 were non-clinical controls. Diagnosis and hallucination presence was determined using the Structured Clinical Diagnostic Interview for DSM-IV TR. AVHs severity was assessed using the Positive and Negative Syndrome Scale. Participants also completed the MATRICS cognitive battery. Results: The bipolar disorder with psychosis group performed better than the schizophrenia group for cognitive domains of Processing speed, Attention, Working memory (WM), and Visual memory. Hierarchical binary logistic regression found that WM significantly predicted presence of AVHs in both psychotic groups, but diagnosis did not significantly increase the predictive value of the model. A hierarchical multiple linear regression found that schizophrenia diagnosis was the only significant predictor of hallucination severity. Conclusions: The findings of this study—the first, to our knowledge, to compare the relationship between AVHs and MATRICS domains across schizophrenia and bipolar disorder with psychosis—support theories that deficits in WM underly the genesis of AVHs. WM potentially represents a shared mechanism of AVHs across diagnoses, supporting dimensional classifications of these psychotic disorders. However, non-cognitive factors predictive of hallucination severity may be specific to schizophrenia.     

Cognitive Subtyping in Schizophrenia: A Latent Profile Analysis

Cognitive dysfunction is a core feature of schizophrenia. The subtyping of cognitive performance in schizophrenia may aid the refinement of disease heterogeneity. The literature on cognitive subtyping in schizophrenia, however, is limited by variable methodologies and neuropsychological tasks, lack of validation, and paucity of studies examining longitudinal stability of profiles. It is also unclear if cognitive profiles represent a single linear severity continuum or unique cognitive subtypes. Cognitive performance measured with the Brief Assessment of Cognition in Schizophrenia was analyzed in schizophrenia patients (n = 767). Healthy controls (n = 1012) were included as reference group. Latent profile analysis was performed in a schizophrenia discovery cohort (n = 659) and replicated in an independent cohort (n = 108). Longitudinal stability of cognitive profiles was evaluated with latent transition analysis in a 10-week follow-up cohort. Confirmatory factor analysis (CFA) was carried out to investigate if cognitive profiles represent a unidimensional structure. A 4-profile solution was obtained from the discovery cohort and replicated in an independent cohort. It comprised of a “less-impaired” cognitive subtype, 2 subtypes with “intermediate cognitive impairment” differentiated by executive function performance, and a “globally impaired” cognitive subtype. This solution showed relative stability across time. CFA revealed that cognitive profiles are better explained by distinct meaningful profiles than a severity linear continuum. Associations between profiles and negative symptoms were observed. The subtyping of schizophrenia patients based on cognitive performance and its associations with symptomatology may aid phenotype refinement, mapping of specific biological mechanisms, and tailored clinical treatments.     

The Effect of Context Processing on Different Aspects of Social Cognition in Schizophrenia

Background: It is well known that individuals with schizophrenia have impaired social cognition. The construct of social cognition involves several components, including perception, interpretation, and the ability to integrate context (Adolphs R. The neurobiology of social cognition. Curr Opin Neurobiol. 2001;11:231–239; Brothers L. The social brain: a project for integrating primate behavior and neurophysiology in a new domain. Concepts Neurosci. 1990;1:27–61). Importantly, a number of studies have suggested that deficits in context processing underlie cognitive dysfunction in schizophrenia (Penn DL, Corrigan PW, Bentall RP, Racenstein JM, Newman L. Social cognition in schizophrenia. Psychol Bull. 1997;121(1):114–132; Green MF, Nuechterlein KH. Should schizophrenia be treated as a neurocognitive disorder? Schizophr Bull. 1999;25:309–319). Thus, the purpose of the current study was to investigate the relationship between context processing and different aspects of social cognition in schizophrenia. Method: Individuals with schizophrenia (n = 41) and the healthy controls (n = 32) participated in this study. The participants completed 2 sections of The Awareness of Social Inference Test: (1) social inference minimal (SI-M) and (2) social inference enriched (SI-E). They also completed face and voice emotion discrimination tasks. In addition, we used the AX-Continuous Performance Test (AX-CPT) to measure context processing and the n-back task to measure working memory more generally. Results: AX-CPT performance in schizophrenia was positively correlated with both SI-M and SI-E performance but not with either the face or the voice discrimination. Furthermore, the correlation between AX-CPT performance and SI-M/SI-E performance was significantly stronger in individuals with schizophrenia than in controls. Conclusion: These results suggest that impairments in context processing are related to inferential components of social cognition in schizophrenia but not to the ability to recognition facial or vocal emotion. As such, deficits in context processing may contribute to deficits in both “hot” and “cold” aspects of cognition in schizophrenia.     

Are there differential deficits in facial emotion recognition between paranoid and non-paranoid schizophrenia? A signal detection analysis

This study assessed facial emotion recognition abilities in subjects with paranoid and non-paranoid schizophrenia (NPS) using signal detection theory. We explore the differential deficits in facial emotion recognition in 44 paranoid patients with schizophrenia (PS) and 30 non-paranoid patients with schizophrenia (NPS), compared to 80 healthy controls. We used morphed faces with different intensities of emotion and computed the sensitivity index (d′) of each emotion. The results showed that performance differed between the schizophrenia and healthy controls groups in the recognition of both negative and positive affects. The PS group performed worse than the healthy controls group but better than the NPS group in overall performance. Performance differed between the NPS and healthy controls groups in the recognition of all basic emotions and neutral faces; between the PS and healthy controls groups in the recognition of angry faces; and between the PS and NPS groups in the recognition of happiness, anger, sadness, disgust, and neutral affects. The facial emotion recognition impairment in schizophrenia may reflect a generalized deficit rather than a negative-emotion specific deficit. The PS group performed worse than the control group, but better than the NPS group in facial expression recognition, with differential deficits between PS and NPS patients.     

General and social cognition in first episode schizophrenia: identification of separable factors and prediction of functional outcome using the IntegNeuro test battery

OBJECTIVE: It is increasingly recognized that cognitive assessments, unlike symptom ratings, provide a reliable predictor of functional outcome in schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized test battery for assessing cognition in first episode schizophrenia. We determined the presence of separable factors of general and social cognition, their equivalence to the consensus domains identified by the NIMH MATRICS project, and their effectiveness in predicting real world functional outcomes. METHOD: Fifty six first episode schizophrenia (FES) patients and 112 matched healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive test battery and FES patients for social functioning (SOFAS) and quality of life (WHOQOL-BREF). RESULTS: Principal components analysis identified i) six factors corresponding to MATRICS domains of general cognition ('Information Processing Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an 'Emotional Intelligence' factor corresponding to the MATRICS social cognition domain, and iii) an additional 'Sensori-Motor Function' factor of general cognition and 'Negativity' factor of social cognition. Patients showed impairments relative to controls across all factors, but especially for Working Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and Negativity. These factors strongly predicted poorer social functioning in FES, along with poorer quality of life in psychological, social, and health satisfaction facets. CONCLUSION: The IntegNeuro battery has utility for assessing separable domains of general and social cognition in FES, which are predictive of real world outcomes. Thus, it may be appropriate for clinical application, including in multi-center trials targeting new treatments for cognition in schizophrenia.