Schizophrenia Research: Cognition

Print ISSN: 2215-0013
Participant demographics. 
Considerable data support the phenomenological and temporal continuity between subclinical psychosis and psychotic disorders. In recent years, neurocognitive deficits have increasingly been recognized as a core feature of psychotic illness but there are few data seeking to elucidate the relationship between subclinical psychosis and neurocogntive deficits in non-clinical samples. The goal of the present study was to examine the relationship between subclinical positive and negative symptoms, as measured by the Community Assessment of Psychic Experiences (CAPE) and performance on the MATRICS Consensus Cognitive Battery (MCCB) in a large (n=303) and demographically diverse non-clinical sample. We found that compared to participants with low levels of subclinical positive symptoms, participants with high levels of subclinical positive symptoms performed significantly better in the domains of working memory (p<.001), verbal learning (p=.007) and visual learning (p=.014). Although comparison of participants with high and low levels of subclinical negative symptoms revealed no differences in MCCB performance, we found that individuals with high levels of subclinical negative symptoms performed significantly better on a measure of estimated IQ (WRAT-3 Reading subtest; p=.02) than those with low levels of subclinical negative symptoms. These results are at odds with prior reports that have generally shown a negative relationship between neurocognitive functioning and severity of subclinical psychotic symptoms, and suggest some potential discontinuities between clinically significant psychotic symptoms and sub-syndromal manifestations of psychosis.
Demographic information from full sample (mean ± SD).
Demographic information from matched sub-sample (mean ± SD).
Task sequence for a Mask trial type.
Working memory capacity estimate K (± SEM) from the sub-sample of K-matched participants. Panel A: Number of items stored (K) for each condition. Panel B: Masking Cost (KDIFF and KRATIO).
Working memory capacity estimate K (± SEM) and Masking Cost from the full sample. Panel A: Number of items stored (K) for each condition. Panel B: Masking Cost (KDIFF and KRATIO).
Although working memory impairment has been well-documented among people with schizophrenia (PSZ), the underlying mechanism of this impairment remains unknown. The present study was conducted in a large sample of PSZ and healthy control subjects (HCS) to test the hypothesis that one putative mechanism – vulnerability to distraction from task-irrelevant stimuli – (1) can account for working memory impairment among PSZ, and (2) is associated with other neurocognitive and clinical variables that are highly predictive of functional outcome in schizophrenia. Participants (127 PSZ and 124 HCS) completed a visual change detection task in which a distractor stimulus (mask) was presented on half of the trials during the delay period between sample and test array. PSZ lost proportionately more information from working memory than did HCS, but this effect was small (Cohen’s d = 0.36–0.38), and large differences between groups in working memory capacity remained when differences in distractibility were factored out. Furthermore, vulnerability to distraction was not strongly associated with any clinical or cognitive variables of interest. These results suggest that, although PSZ may be somewhat more susceptible to distraction than HCS, this impairment is unlikely to be a significant factor accounting for the robust capacity deficits observed in this population.
Sample characteristics of the patient and healthy control groups.
Outcome measures data. Averaged performance (±SEM) before (blue bars) and after (red bars) SocialVille training. (A) Median reaction time (RT, in ms) for correct responses on the PROID task; (C) Facial recognition test (Penn) data: median reaction time (RT, in ms) for immediate (left) and delayed (right) recall of faces. *p values and Cohen’s d values are shown; n.s. non-significant.
Examples of the SocialVille tasks. Top: Face Perception (‘S Face Match’) exercise. Once the user clicks on the ‘start’ button, a face appears for a short duration, followed by a visual mask for 500 ms. Then, an array of faces appears, and the user should select the target face. A feedback is provided following the selection. The duration of presentation of the target face is adaptively determined based on the user’s responses. Middle and Bottom: Gaze Perception (‘S Gaze Match’; middle panel) and Emotion Identification (‘S Face Emotion ID’; bottom panel). The same trial structure as described above is employed for these exercises as well, but here the user needs to either match the gaze direction of the target face (’S Gaze Match’) or identify the facial expression.
Outcome measures data. Averaged performance (+SEM) before (blue bars) and after (red bars) training. (A) Global Functioning Scale (GFS), Role Current and Social Current subscales; (B) Social Functioning Scale (SFS), interpersonal communication and prosocial subscales; (C) Behavioral Inhibition/Behavioral Activation (BIS/BAS) test, BIS total and BAS drive subscales. (D) Temporal Experience of Pleasure Scale (TEPS), anticipatory (left) and consummatory (right) subscales.
Normalized SocialVille Exercise-based Assessment Data. Averaged (+SEM) Z score changes on the ‘speeded’ (A), WM (B), and composites (C) SocialVille exercises following training. The composites were derived as averages across all exercises in the same category; the ‘total’ composite is the average across all exercises (excluding prosody). Note the different scales on the three panels. *p<.05; **p<.01; ***p<.005.
Background Pervasive social cognition deficits are evident early in the course of schizophrenia and are directly linked to functional outcome, making them an important target for intervention. Here, we tested the feasibility of use, and initiated the evaluation of efficacy, of a novel, neuroplasticity-based online training program (SocialVille) in young adults with schizophrenia. Methods Schizophrenia patients (n = 17) completed 24 hours of online SocialVille game play either from home or at a clinic, over a 6–10 week period. We examined training feasibility, gains on the SocialVille exercises relative to matched healthy controls (n = 17), and changes on measures of social cognition, social functioning, global functioning and motivation. Results Subjects adhered to training requirements, and rated SocialVille in the medium to high range in satisfaction, enjoyment, and ease of use. Subjects demonstrated significant, large improvements on the speeded SocialVille tasks, and small to moderate improvements on the working memory tasks. Post-training performance on the SocialVille tasks were similar to initial performance of the healthy controls. Subjects also showed improvements on standard measures of social cognition, social functioning, and motivation. No improvements were recorded for emotion recognition indices of the MSCEIT, or on quality of life scales. Conclusion This study provides an initial proof of concept for online social cognition training in schizophrenia. This form of training demonstrated feasibility and resulted in within-subject gains in social functioning and motivation. This pilot study represents a first step towards validating this training approach; randomized controlled trials, now underway, are designed to confirm and extend these findings.
Differences between future psychotic disorder patients and matched controls on key themes. 
Background Previous research has shown that people with psychotic disorders have impaired functioning prior to the onset of the illness. The goal of this study is to obtain a detailed, in depth, analysis of the characteristics of premorbid impairment. Methods In this study we examined summaries of interviews with 20 male adolescents who were later diagnosed with non-affective psychotic disorders and compared them to interviews conducted with 20 matched controls without psychiatric disorders. The current study applied a qualitative analysis, performed in the following stages: each interview was read thoroughly by two blinded raters with no a-priori hypothesis, and then key themes and statements were identified and organized into meaningful domains. Afterwards, the frequency of each item was calculated and comparisons between the groups were performed. Results Future non-affective psychotic disorder patients were more likely to be described as strange or different, be involved in violent behavior, experience difficulties in educational functioning and peer integration, deal with problems in everyday functioning and have an avoidant interpersonal conflict resolution style in comparison with matched controls without psychiatric disorders. In addition, future patients experienced more stressful life events and dealt with these stressors more poorly in comparison with controls. Conclusions The findings of this unique historical-prospective qualitative analysis of interviews performed before the onset of psychosis, confirmed previous findings of premorbid abnormality of future non-affective psychosis patients. Using qualitative analysis enabled obtaining a more in-depth understanding of the real-life experience of the premorbid period among patients with non-affective psychotic disorders.
Average number of errors and time for patients and healthy controls on VRFCAT objectives.
Introduction Assessment of functional capacity is an intrinsic part of determining the functional relevance of response to treatment of cognitive impairment in schizophrenia. Existing methods are highly and consistently correlated with performance on neuropsychological tests, but most current assessments of functional capacity are still paper and pencil simulations. We developed a computerized virtual reality assessment that contains all of the components of a shopping trip. Methods We administered the Virtual Reality Functional Capacity Assessment Tool (VRFCAT) to 54 healthy controls and to 51 people with schizophrenia to test its feasibility. Dependent variables for the VRFCAT included time to completion and errors on 12 objectives and the number of times that an individual failed to complete an objective. The MATRICS Consensus Cognitive Battery (MCCB) and a standard functional capacity measure, the UCSD Performance-Based Skills Assessment-Brief (UPSA-B), were administered to the patients with schizophrenia. Results Patients with schizophrenia performed more poorly than healthy controls on 10/11 of the time variables, as well as 2/12 error scores and 2/12 failed objectives. Pearson correlations for 7 of 15 VRFCAT variables with MCCB composite scores were statistically significant. Conclusion These results provide support for the possibility of computerized functional capacity assessment, but more substantial studies are required.
Summary of included studies. 
Abbreviations: CAST = Computer assisted cognitive strategy training, CEA = cost-effectiveness analysis, CRT = cognitive remediation therapy, NET = neurocognitive enhancement therapy, QoL = quality of life, PLP = Patient-Level Predictors, RCT = randomized controlled trial, SPD = schizotypal personality disorder, TSSN = Training of self-management skills for negative symptoms. 
Background: The primary focus of research in schizophrenia has been on the positive symptoms, with findings that clearly establish their economic burden. More recently, research has expanded to focus on another core symptom of schizophrenia, namely cognitive impairments. While this work has established the adverse impact of cognitive impairments associated with schizophrenia (CIAS) on functional outcomes, their relationship to the economic impact of schizophrenia has not been systematically evaluated. Objective: The aim of this research was to perform a systematic literature review identifying evidence that evaluates: 1) the economic impact of CIAS and its treatments, including health-state utilities, and 2) the economic evidence associated with improvements in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the University of California Performance Skills Assessment (UPSA). Method: A systematic search of articles published from January 1999–April 2013 was conducted. Studies reporting direct costs, indirect costs, and quality of life impacts of CIAS and costs of CIAS interventions were reviewed. Results: Forty-three studies met inclusion criteria. Twenty-four focused on indirect costs (work-related outcomes) associated with cognitive impairments and 14 studies included residential status outcomes. Four studies concentrated on the direct cost of cognitive remediation therapy. Three studies reported quality of life outcomes, but none used health-state utilities. Eight studies focused on the UPSA and its relationship to community outcomes. Only two studies were cost-effectiveness analyses. Conclusions: Despite the growing scientific literature relating CIAS to adverse outcomes, the translation of outcomes into economic outcomes is seldom reported. Should novel pharmacotherapies and/or psychosocial treatments require reimbursement from health authorities and/or other payers, many gaps warrant attention in order to demonstrate the economic value of these therapies.
Schizophrenia Research: Cognition will serve an important function – a place where interests converge and investigators can learn about the recent developments in this area. This new journal will provide rapid dissemination of information to people who will make good use of it. In this initial article, we comment globally on the study of cognition in schizophrenia: how we got here, where we are, and where we are going. The goal of this first article is to place the study of cognition in schizophrenia within a historical and scientific context. In a field as richly textured as ours it is impossible to hit all the important areas, and we hope the reader will forgive our omissions. Phrased in cognitive terms, our limited presentation of the past is a matter of selective memory, the present is a matter of selective attention, and the future is a matter of selective prospection. This broad introduction emphasizes that cognition in schizophrenia provides clues to pathophysiology, treatment, and outcome. In fact, the study of cognitive impairment in schizophrenia has become wholly intertwined with the study of schizophrenia itself.
Demographic information by group.
Prediction of SLOF Interpersonal domain (interpersonal performance) at 18month follow-up by SSPA (interpersonal competence) at baseline, by symptom group.
Prediction of SLOF (activities in the community) at 18month follow-up by UPSA (adaptive competence) at baseline, by symptom group.
Background Many individuals with schizophrenia experience remission of prominent positive symptoms but continue to experience impairments in real world functioning. Residual negative and depressive symptoms may have a direct impact on functioning and impair patients' ability to use the cognitive and functional skills that they possess (competence) in the real world (functional performance). Methods One hundred thirty-six individuals (100 men, 36 women) with schizophrenia were classified as having primarily positive symptoms, primarily negative symptoms, primarily depressive symptoms, or undifferentiated symptom profiles. Performance based measures of cognition and adaptive and interpersonal functional competence were used, along with ratings of real world behavior by high contact clinicians. Assessments were performed at baseline and at an 18-month follow-up. Results The relationships between neurocognition and capacity/performance were not moderated by symptom group ps > .091; neurocognition predicted capacity and performance for all groups ps < .001. The relationship between adaptive competence and adaptive performance was moderated by symptom group, ps < .01, such that baseline competence only predicted future performance ratings for participants with primarily positive or undifferentiated symptoms, and not for individuals with primarily negative or depressive symptoms. This same moderation effect was found on the relationship between interpersonal competence and interpersonal performance, ps < .002. Conclusions Residual negative and depressive symptoms are distinct constructs that impede the use of functional skills in the real world. Depressive symptoms are often overlooked in schizophrenia but appear to be an important factor that limits the use of functional ability in real world environments.
Demographic information and performance-based scores for two different treatment sites.
Job status across the groups.
Change in job status from best job to most recent job.
Vocational functioning is markedly impaired in people with schizophrenia. In addition to low rates of employment, people with schizophrenia have been reported to be underachieved compared to other family members. Among the causes of this vocational impairment may be cognitive deficits and other skills deficits, as well as social factors impacting on opportunities for employment. In this study, we examined two separate samples of people with schizophrenia who differed in their educational and social backgrounds. We compared personal and maternal education in people with schizophrenia attending an outpatient rehabilitation facility (n = 57) or receiving outpatient services at a VA medical center (n = 39). The sample as a whole showed evidence of decline in vocational status from their best job to their most recent job. Patients attending a rehabilitation facility had completed less education than their mothers, while the VA patients completed more. Differences between personal and maternal education predicted the difference in status between best and latest jobs in the sample as a whole. VA patients were more likely to be living independently and performed better on a measure of functional capacity than the rehabilitation sample. These data implicate vocational decline in schizophrenia and also suggest that this decline may originate prior to the formal onset of the illness. At the same time, vocational outcomes appear to be related to social opportunities.
Determinants of disability in schizophrenia.
Multimodal skills-based performance intervention.
Despite 50 years of pharmacological and psychosocial interventions, schizophrenia remains one of the leading causes of disability. Schizophrenia is also a life-shortening illness, caused mainly by poor physical health and its complications. The end result is a considerably reduced lifespan that is marred by reduced levels of independence, with few novel treatment options available. Disability is a multidimensional construct that results from different, and often interacting, factors associated with specific types and levels of impairment. In schizophrenia, the most poignant and well characterized determinants of disability are symptoms, cognitive and related skills deficits, but there is limited understanding of other relevant factors that contribute to disability. Here we conceptualize how reduced physical performance interacts with aging, neurobiological, treatment-emergent, and cognitive and skills deficits to exacerbate ADL disability and worsen physical health. We argue that clearly defined physical performance components represent underappreciated variables that, as in mentally healthy people, offer accessible targets for exercise interventions to improve ADLs in schizophrenia, alone or in combination with improvements in cognition and health. And, finally, due to the accelerated aging pattern inherent in this disease – lifespans are reduced by 25 years on average – we present a training model based on proven training interventions successfully used in older persons. This model is designed to target the physical and psychological declines associated with decreased independence, coupled with the cardiovascular risk factors and components of the metabolic syndrome seen in schizophrenia due to their excess prevalence of obesity and low fitness levels.
The present investigation explores the relationship between facial emotion recognition (FER) and symptom domains in three groups of schizophrenia spectrum patients (43 ultra-high-risk, 50 first episode and 44 multi-episode patients) in which the existence of FER impairment has already been demonstrated. Regression analysis showed that symptoms and FER impairment are related in multi-episode patients, regardless of the illness duration. We suggest that the link between symptoms and FER impairment is involved in the progression of the disease.
Left to right: Option Characteristic Curves. Item 1: Negative Domain, Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; Item 3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain, Active Social Withdrawal. Item Characteristic Curves: Item 1: Negative Domain, Blunted Affect; Item 2: Negative Domain, Emotional Withdrawal; Item 3: Negative Domain, Poor Rapport; Item 4: Negative Domain, Passive Apathetic Social Withdrawal; Item 5: Negative Domain, Lack of Spontaneity and Flow of Conversation; Item 6: Negative Domain, Motor Retardation; Item 7: Negative Domain, Active Social Withdrawal.
Left to right: Option Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4: Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack of Judgment and Insight. Item Characteristics Curves. Item 1: Positive Domain, Delusions; Item 2: Positive Domain, Hallucinatory Behavior; Item 3: Positive Domain, Grandiosity; Item 4:; Positive Domain, Suspiciousness/Persecution; Item 5: Positive Domain, Stereotyped Thinking; Item 6: Positive Domain, Somatic Concerns; Item 7: Positive Domain, Unusual Thought Content; Item 8: Positive Domain, Lack of Judgment and Insight.
Example of an ‘ideal’ item characteristic curve (ICC).
Left to right: Option Characteristic Curves (graphs shows 7 overlapping lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain; Depression. Item Characteristic Curves (graphs show one line with green intersecting lines). Item 1: Anxiety Domain, Anxiety; Item 2: Anxiety Domain, Guilt Feelings; Item 3: Anxiety Domain, Tension; Item 4: Anxiety Domain, Depression.
Example of an ‘ideal’ option characteristic curve (OCC).
Background The Positive and Negative Syndrome Scale (PANSS) assesses multiple domains of schizophrenia. Evaluation of each of these domains was conducted to assess differences in the characteristics of psychopathology and their relative predominance in sub-populations. Method Subjects (N = 1,832) with DSM-IV schizophrenia were represented in three sub-populations: First Episodes, n = 305, Chronic Inpatients, n = 694, and Ambulatory Outpatients, n = 833. Nonparametric Item Response Analysis (IRT) was performed with Option Characteristic Curves (OCC), Item Characteristic Curves (ICC), slopes and item biserial correlation. Items were characterized as Very Good, Good, or Weak based on specified operational criteria for item selection. Results First episode patients were represented by negative, disorganized hostility and anxiety. Some negative domain items (Poor Rapport, Passive/Apathetic Social Withdrawal) and most positive domain items were scored as Weak. For chronic inpatients, all items of the anxiety domain and some items of the positive domain (Suspiciousness/Persecution, Stereotyped Thinking, Somatic Concerns) were Weak; for all other domains, items were Very Good or Good. For ambulatory outpatients, most items in the anxiety and hostility domain were scored as Weak. The majority of PANSS items were either Very Good or Good at assessing the overall illness severity: chronic inpatients (73.33%, 22 items), first episodes (60.00%, 18 items), and only 46.67% (14 items) in the ambulatory group. Conclusion Findings confirm differences in symptom presentation and predominance of particular domains in subpopulations of schizophrenia. Identifying symptom domains characteristic of subpopulations may be more useful in assessing efficacy endpoints than total or subscale scores.
Participant characteristics
Intercorrelations, multicollinearity statistics and internal consistency for all scales
Regression of schizotypy on loneliness by cohort
Loneliness is common in psychosis and occurs along a continuum. Here we investigate inter-relationships between loneliness, three-dimensional schizotypy, and depressive symptoms before and during the COVID-19 pandemic. The sample included 507 university students (48.3% participated before and 51.7% during the COVID-19 pandemic) who completed the Multidimensional Schizotypy Scale-Brief, the Counseling Center Assessment of Psychological Symptoms depression scale and the University of California, Los Angeles Loneliness Scale. Schizotypy and depression scores were regressed onto loneliness individually and in multiple regressions. The cohorts did not differ in any of the schizotypy domains (all p > .29). Depressive symptoms (p = .05) and loneliness (p = .006) were higher during the pandemic than before. Across cohorts, loneliness was significantly associated with positive (β = 0.23, p < .001), negative (β = 0.44, p < .001), and disorganised schizotypy (β = 0.44, p < .001), and with depression (β = 0.72, p < .001). Schizotypy together explained a significant amount of variance in loneliness (R² = 0.26), with significant associations with positive (β = −0.09, p = .047), negative (β = 0.31, p < .001) and disorganised schizotypy (β = 0.34, p < .001). When depression was included (β = 0.69, p < .001), only positive (β = −0.09, p = .008) and negative schizotypy (β = 0.22, p < .001) significantly predicted loneliness. When all schizotypy dimensions and depression were considered together, only negative schizotypy and depression significantly predicted loneliness. Loneliness and depressive symptoms were higher during the pandemic, but this did not relate to cohort differences in schizotypy.
A. Cartoon of the visual system showing that separate magnocellular (M) and parvocellular (P) pathways project differentially to dorsal vs. ventral visual streams. Properties of the pathways are indicated in the table. B. Flattened map of visual cortex showing primary (V1) and secondary (V2-V4) visual regions (legend shown at bottom). Regions showing preferential response to low, medium and high spatial frequency stimulation are shown in red, yellow and blue, respectively. Schizophrenia patients show significant reductions in response to low spatial frequency stimuli (red areas), whereas response to high spatial frequency stimulation (blue regions) remains relatively intact. From Martinez et al. (2008). 
Schizophrenia is increasingly being viewed as a “whole brain” disorder with deficits affecting widespread cortical and subcortical networks. Within this context, studies of visual cortical function may be particularly important both because visual processing deficits directly affect social and occupational function and because these systems are well characterized at the basic science level, permitting informative translational research. This article summarizes a conference on visual processing dysfunction in schizophrenia held in Lausanne, Switzerland from June 30 to July 1, 2014 and introduces this special issue. Speakers focused on multiple aspects of visual dysfunction in schizophrenia using behavioral, neurophysiological and fMRI-based approaches. Four main themes emerged. First was a focus on response disturbances within the early visual system, using paradigms such as sensory EEG and MEG-based responses. Second, behavioral deficits were noted in processing related to local interaction within visual regions, using paradigms such as Vernier acuity or contour integration. These deficits provided potential model systems to understand impaired connectivity within the brain in schizophrenia more generally. Third, several visual measures were found to correlate highly with symptoms and/or neurocognitive processing. Deficits in contour integration, for example, correlated highly with conceptual disorganization, whereas perceptual instability correlated with delusion formation. These findings highlight links between perceptual-level disturbance and clinical manifestation. Finally, the potential involvement of specific neurotransmitter receptors, including N-methyl-D-aspartate (NMDA)-type glutamate receptors and alpha7 nicotinic receptors were discussed as potential etiological mechanisms. Overall, the meeting highlighted the contributions of visual pathway dysfunction to the etiopathogenesis of neurocognitive dysfunction in schizophrenia.
Demographic table.
Results of the microstate analysis reveal temporal differences between groups. In the four graphs, blue bars represent the control adolescents, orange bars the 22q11DS adolescent patients, purple bars the adult controls, and red ones the schizophrenia patients. 1. The spatial configuration of the four microstate classes (A, B, C, D) across groups. 2–5. The temporal microstate parameters frequency of occurrence, mean duration, time coverage and global explained variance (GEV) are significantly different across groups for microstate classes C and D. 3. Missing star on horizontal bar marks a statistical trend (p=0.09). Error bars indicate the standard deviation (see Table 2).
Microstate syntax analysis shows significant differences in transition probabilities between patient and control groups. 1. Dark arrows indicate significant increases in transition probabilities from microstate class B towards class C in the 22q11DS patients compared to adolescent controls. 2. Similarly, syntax transitions of SZ are significantly increased from A, B, C and D microstate classes toward the class C microstate of adult controls. 3. Conversely, adult controls show significant increased transition probabilities from A, B and C microstate classes towards class D microstate when compared with SZ. SZ=schizophrenia patients.
Schizophrenia is a complex psychiatric disorder and many of the factors contributing to its pathogenesis are poorly understood. In addition, identifying reliable neurophysiological markers would improve diagnosis and early identification of this disease. The 22q11.2 deletion syndrome (22q11DS) is one major risk factor for schizophrenia. Here, we show further evidence that deviant temporal dynamics of EEG microstates are a potential neurophysiological marker by showing that the resting state patterns of 22q11DS are similar to those found in schizophrenia patients. The EEG microstates are recurrent topographic distributions of the ongoing scalp potential fields with temporal stability of around 80 ms that are mapping the fast reconfiguration of resting state networks. Five minutes of high-density EEG recordings was analysed from 27 adult chronic schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28 adolescent controls. In both patient groups we found increased class C, but decreased class D presence and high transition probabilities towards the class C microstates. Moreover, these aberrant temporal dynamics in the two patient groups were also expressed by perturbations of the long-range dependency of the EEG microstates. These findings point to a deficient function of the salience and attention resting state networks in schizophrenia and 22q11DS as class C and class D microstates were previously associated with these networks, respectively. These findings elucidate similarities between individuals at risk and schizophrenia patients and support the notion that abnormal temporal patterns of EEG microstates might constitute a marker for developing schizophrenia.
Part A: The z-scores for six BACS subdomains for patients with schizophrenia (Sch, solid line) and those with bipolar disorder (BP, dotted line) relative to the healthy control subjects for which the mean and standard deviation were set to zero and one, respectively. Ⓐ,verbal memory (list learning); Ⓑ, digit sequencing task;
Part A: Association between 115 SNPs mapping to 22q11.2 and BACS cognitive subdomains in patients with schizophrenia. Part B: Association between 115 SNPs mapping to 22q11.2 and BACS cognitive subdomains in controls. Vertical lines represent P-values depicted on a logarithmic scale. SNPs were arranged on the horizontal lines in order of chromosomal position. P-values were determined by running 10,000 permutations using the max (T) procedure adjusted for multiple tests implemented in PLINK version 1.0.7. The significance level was set at 0.00833 (0.05/6) to correct for the six BACS subdomains. SNPs that showed at least a nominally significant level (P < 0.05) were denoted over P value peaks.
22q11.2 heterozygous multigene deletions confer an increased risk of schizophrenia with marked impairment of cognition. We explored whether genes on 22q11.2 are associated with cognitive performance in patients with idiopathic schizophrenia. A total of 240 schizophrenia patients and 240 healthy controls underwent the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS) and were genotyped for 115 tag single-nucleotide polymorphisms (tag SNPs) at the 22q11.2 region using the golden gate assay (Illumina®). Associations between z-scores of the BACS cognitive domains and SNPs and haplotypes were analyzed using linear regression in PLINK 1.07. An additional set of 149 patients with bipolar disorder were included for cognitive assessment and selected SNPs were genotyped using real-time PCR. Patients with schizophrenia and bipolar disorder showed qualitatively comparable profiles of cognitive impairment across BACS subdomains, as revealed by significant correlation between the two groups in the resulting cognitive effect sizes relative to controls. rs4819522 (TBX1) and rs2238769 (UFD1L) were significantly and nominally associated, respectively, with symbol coding in patients with schizophrenia. Haplotype analyses revealed that haplotypes containing the A allele at rs4819522 and G allele at rs2238769 showed significant negative associations with symbol coding in patients with schizophrenia. There was no effect of any haplotypes on cognition in patients with bipolar disorder. Our results have implications for the understanding of the role of haplotypes of UFD1L and TBX1 genes associated with symbol coding in patients with schizophrenia. Further replication studies in a cohort of newly diagnosed patients and other ethnicities are warranted.
A) Implicit salience paradigm. Instructed like a target-detection task, participants saw one out of four cues (grey and colorful triangles and squares, see B)) that was followed by a coin (10 cents) representing reward or a blue circle representing a neutral outcome. The task was to respond to the outcome by pressing the assigned button. In a dynamic design, either the shape of the stimulus or the color probabilistically predicted the outcome (e.g., for extra-dimensional relevance of shape: 80 % reinforcement for triangles and 20 % for squares and this intra-dimensional association reversed every 20 trials). Whilst at the same time, the other extra-dimension (e.g., color) was irrelevant (50% reinforcement following colorful and grey cues). The extra-dimensional relevance reversed after the first half of trials (e.g., trial 1?80 shape relevant, trial 81?160 color relevant). The order of relevant features and reinforced manifestations was balanced across participants. They were told not to pay attention to the preceding cues. But in order to prime the implicit categorization of color and shape, participants were asked to verbally describe the cues before a training session (20 trials) that only used one cue not appearing in the main experiment. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)  
Partial regression plot with standardized negative symptoms sum score (PANSS) predicting implicit aberrant salience (ß = 0.431; t = 2.11; p = 0.040).
Behavioral data.
Pattern matrix.
Suspecting significance behind ordinary events is a common feature in psychosis and it is assumed to occur due to aberrant salience attribution. The Salience Attribution Test (SAT; Roiser et al., 2009) measures aberrant salience as a bias towards one out of two equally reinforced cue features as opposed to adaptive salience towards features indicating high reinforcement. This is the first study to validate the latent constructs involved in salience attribution in patients. Forty-nine schizophrenia patients and forty-four healthy individuals completed the SAT, a novel implicit salience paradigm (ISP), a reversal learning task and a neuropsychological test battery. First, groups were compared on raw measures. Second and within patients, these were correlated and then used for a principal component analysis (PCA). Third, sum scores matching the correlation and component pattern were correlated with psychopathology. Compared to healthy individuals, patients exhibited more implicit aberrant salience in the SAT and ISP and less implicit and explicit adaptive salience attribution in the SAT. Implicit aberrant salience from the SAT and ISP positively correlated with each other and negatively with reversal learning. Whereas explicit aberrant salience was associated with cognition, implicit and explicit adaptive salience were positively correlated. A similar pattern emerged in the PCA and implicit aberrant salience was associated with negative symptoms. Taken together, implicit aberrant salience from the SAT and ISP seems to reflect an automatic process that is independent from deficient salience ascription to relevant events. Its positive correlation with negative symptoms might reflect motivational deficits present in chronic schizophrenia patients.
Behavioural data.
Visual analogue scale (VAS) probability ratings in schizophrenia patients with treatment-resistant delusions (TRS) and controls. Controls exhibited significantly greater explicit adaptive salience (the difference in VAS rating between high and low probability stimuli) than TRS patients [controls: mean=33.22, SD=21.57; patients: mean=7.85, SD=12.03; F(1,47)=20.997, P<0.001]. This group difference was driven by a reduction in the ratings for high probability stimuli in TRS patients (* indicates P<0.001), while there was no difference between the groups for the ratings of low probability stimuli. Error bars represent standard errors of the mean.
Objective: It has been suggested that positive psychotic symptoms reflect 'aberrant salience'. Previously we provided support for this hypothesis in first-episode schizophrenia patients, demonstrating that delusional symptoms were associated with aberrant reward processing, indexed by the Salience Attribution Test (SAT). Here we tested whether salience processing is abnormal in schizophrenia patients with long-standing treatment-refractory persistent delusions (TRS). Method: Eighteen medicated TRS patients and 31 healthy volunteers completed the SAT, on which participants made a speeded response to earn money in the presence of cues. Each cue comprised two visual dimensions, colour and form. Reinforcement probability varied over one of these dimensions (task-relevant), but not the other (task-irrelevant). Results: Participants responded significantly faster on high-probability relative to low-probability trials, representing implicit adaptive salience; this effect was intact in TRS patients. By contrast, TRS patients were impaired on the explicit adaptive salience measure, rating high-probability stimuli less likely to be associated with reward than controls. There was little evidence for elevated aberrant salience in the TRS group. Conclusion: These findings do not support the hypothesis that persistent delusions are related to aberrant motivational salience processing in TRS patients. However, they do support the view that patients with schizophrenia have impaired reward learning.
Difference in mean LI score (ms) across all four trial blocks in relation to current use (n = 82) and non-use (n = 263) of cannabis. Error bars represent 95% Confidence Intervals from the respective in-text linear mixedeffects model.
Characteristics of the sample population (n = 346).
Aberrant salience processing may underlie the link between cannabis and psychosis, as posited in individuals with schizophrenia or high schizotypy. We investigated the relative effects of cannabis use, schizotypy status, and self-reported aberrant salience experiences on salience processing, measured using a latent inhibition (LI) task (Granger et al., 2016), in a non-clinical population. A university sample of 346 participants completed the Schizotypal Personality Questionnaire (SPQ), Aberrant Salience Inventory (ASI) the modified Cannabis Experience Questionnaire (CEQmv) and the LI task. Regression models and parallel (Bayesian and frequentist) t-tests or ANOVA (or non-parametric equivalents) examined differences in LI based on lifetime or current cannabis use (frequent use during previous year), as well as frequency of use. Mann-Whitney U tests assessed differences in SPQ and ASI scores based on current cannabis use. Neither lifetime nor current cannabis use was associated with significant change in LI scores. Current cannabis use was associated with both higher ‘Disorganised’ and ‘Cognitive-perceptual’ SPQ dimension scores and higher total and sub-scale ASI scores. No association was observed between LI score and SPQ total and dimension scores. Higher scores on ‘Senses sharpening’ and the ‘Heightened cognition’ ASI subscales predicted decreased LI scores. These data support previous findings of no association between cannabis use and abnormality in other associative learning tasks in young non-clinical populations, and elaborate the previously demonstrated association between self-reported cannabis use, schizotypy and aberrant salience. The association between dimensions of ASI and LI performance suggests this task may have potential as an experimental measure of aberrant salience.
Differences among the Schizophrenia Participants who reported No Sadness Vs. Occasional Sadness and Participants with Bipolar Disorder.
Objectives People with schizophrenia have challenges in their self-assessments of everyday functioning and those who report no sadness also tend to overestimate their everyday functional abilities. While previous studies were cross-sectional, this study related longitudinal assessments of sadness to self-reports of abilities in domains of everyday functioning and cognitive abilities. Methods 71 people with bipolar illness (BPI) were compared to 102 people with schizophrenia (SCZ). Participants were sampled 3 times per day for 30 days with a smartphone-based Ecological Momentary Assessment (EMA) survey. Each survey asked where they were, with whom they were, what they were doing, and if they were sad. Performance based assessments of executive functioning, social competence, and everyday activities were collected after the EMA period, at which time the participants and observers were asked to provide ratings of three different domains of everyday functioning and neurocognitive ability. Results 18% of participants with SCZ reported that they were never sad on any one of the 90 EMA surveys. Reports of never being sad were associated with overestimated functioning compared to observers and SCZ participants who reported that they were never sad were more commonly home and alone than both SCZ participants who reported occasional sadness and participants with BPI. These participants reported being significantly happier than all people in the study. Implications Reporting that you were never sad was associated with overestimation of everyday functioning and cognitive abilities. Although participants who were never sad did not perform more poorly on objective measures than those were occasionally sad, their self-assessed functioning was significantly elevated. These data suggest that negative symptoms constructs such as reduced emotional experience need to consider reduced ability to subjectively evaluate emotional experience as a feature of negative symptoms.
Study feasibility.
Cognitive remediation (CR) is an effective treatment for schizophrenia. However, issues such as motivational impairments, geographic limitations, and limited availability of specialized clinicians to deliver CR, can impede dissemination. Remote delivery of CR provides an opportunity to implement CR on a broader scale. While empirical support for the efficacy of in-person CR is robust, the evidence-base for virtual delivery of CR is limited. Thus, in this review we aimed to evaluate the feasibility and acceptability of remote CR interventions. Nine (n = 847) fully remote and one hybrid CR intervention were included in this review. Attrition rates for remote CR were generally high compared to control groups. Acceptability rates for remote CR interventions were high and responses from caregivers were positive. Further research using more methodologically rigorous designs is required to evaluate appropriate adaptations for remote treatment and determine which populations may benefit more from remote CR.
Background: Delusions, a core symptom of schizophrenia, are thought to arise from an alteration in predictive coding mechanisms that underlie perceptual inference. Here, we aimed to empirically test the hypothesized link between delusions and perceptual inference. Method: 28 patients with schizophrenia and 32 healthy controls matched for age and gender took part in a behavioral experiment that assessed the influence of stabilizing predictions on perception of an ambiguous visual stimulus. Results: Participants with schizophrenia exhibited a weaker tendency towards percept stabilization during intermittent viewing of the ambiguous stimulus compared to healthy controls. The tendency towards percept stabilization in participants with schizophrenia correlated negatively with delusional ideation as measured with a validated questionnaire. Conclusion: Our results indicate an association between a weakened effect of sensory predictions in perceptual inference and delusions in schizophrenia. We suggest that attenuated predictive signaling during perceptual inference in schizophrenia may yield the experience of aberrant salience, thereby providing the starting point for the formation of delusions.
Intercorrelations of BLERT variables in the two samples.
Correlations of BLERT confidence, performance, and response times with self-reported clinical, functional, and ability variables.
Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that reduced awareness of performance may be associated with disability. However, overconfidence is common in healthy individuals as well. This study examines the correlations between performance on a social cognitive test, confidence in performance, effort allocated to the task, and correlates of confidence in patients with schizophrenia and healthy controls (HC). Measures included self-reports of depression, social cognitive ability, and social functioning. A performance-based emotion recognition test assessed social cognitive performance and provided the basis for confidence judgments. Although schizophrenia patients had reduced levels of overall confidence, there was a substantial subset of schizophrenic patients who manifested extreme overconfidence and these people had the poorest performance and reported the least depression. Further, a substantial number of HC over-estimated their performance as well. Patients with schizophrenia, in contrast to HC, did not adjust their effort to match task difficulty. Confidence was minimally related to task performance in patients but was associated with more rapid decisions in HC, across both correct and incorrect responses. Performance on social cognitive measures was minimally related to self-reports of social functioning in both samples. These data suggest global self-assessments are based on multiple factors, with confidence affecting self-assessments in the absence of feedback about performance.
Supplementary Table 2 section details parameters used in ML models. Supplementary Table 3 shows the per- formance of various ML models on classification tasks and associatedEffect sizes: Cohen's d, T-value and p-value over 5 emotions, and Combined for ER40: A) RT B) CR and C) Correct (Corr) across the groups (HC & SZ).
Performance of ML on ER40 and BLERT datasets compared to performance inferred from t-tests in SCOPE study. (Classification target: SZ vs. HC). For ER401, 120 features (cognition: 40 RT, 40 Corr and meta-cognition: 40 CR) were considered while for BLERT 63 features (cognition: 21 RT, 21 Corr and meta-cognition: 21 CR) were considered as input.
People with schizophrenia (SZ) process emotions less accurately than do healthy comparators (HC), and emotion recognition have expanded beyond accuracy to performance variables like reaction time (RT) and confidence. These domains are typically evaluated independently, but complex inter-relationships can be evaluated through machine learning at an item-by-item level. Using a mix of ranking and machine learning tools, we investigated item-by-item discrimination of facial affect with two emotion recognition tests (BLERT and ER-40) between SZ and HC. The best performing multi-domain model for ER40 had a large effect size in differentiating SZ and HC (d = 1.24) compared to a standard comparison of accuracy alone (d = 0.48); smaller increments in effect sizes were evident for the BLERT (d = 0.87 vs. d = 0.58). Almost half of the selected items were confidence ratings. Within SZ, machine learning models with ER40 (generally accuracy and reaction time) items predicted severity of depression and overconfidence in social cognitive ability, but not psychotic symptoms. Pending independent replication, the results support machine learning, and the inclusion of confidence ratings, in characterizing the social cognitive deficits in SZ. This moderate-sized study (n = 372) included subjects with schizophrenia (SZ, n = 218) and healthy controls (HC, n = 154).
Baseline values for unstandardized variables.
Illness self-management mixed effects model.
Substance use exacerbates psychosis, mania, depression, and poor functioning in people with first episodes of psychosis (FEP) and is associated with poor treatment outcomes, even when it does not reach the level of a formal disorder. Impaired insight and substance use are common issues that may interfere with treatment outcomes among people experiencing FEP, yet both are treatable. Improvements in these domains are associated with better outcomes. Low insight could increase risk for substance use by impairing the ability to self-appraise and assess consequences. Introspective accuracy (IA) is understudied in this area and is one way of considering self-appraisal. This study is an archival review using data collected from NAVIGATE, a coordinated specialty care program treating people with FEP. IA was operationalized as the difference between clinician and client ratings of substance use. We tested whether IA changed over one year of treatment and whether those changes occurred alongside changes in symptoms and illness self-management. No changes in IA were detected in relation to illness self-management. Changes in IA for substance use occurred midway through treatment—individuals with greater symptom remission had more overconfident IA. Prior research on insight has shown a paradox where greater insight accompanies more symptoms. However, past research has also shown a relationship between IA and functional outcomes, like illness self-management, and that overconfidence in one domain can positively bias clinician ratings in another. Our findings suggest either a positive bias for ratings associated with overconfident IA or an insight paradox type effect.
Experimental interval reproduction task. (A) Sequence of events during a trial. First, participants' attentions were fixated on a cross, and they were instructed to maintain fixation throughout the trial. After a random delay (0.5-1.2 s), a Gaussian patch (visual disk) was displayed for a specific interval (sample interval). Participants were instructed to reproduce the interval by pressing and holding the space key when the word 'reproduction' appeared. (B) Distribution of sample intervals. The wide distribution width was designed to produce high levels of uncertainty; the narrow distribution width was designed to produce low levels of uncertainty. The narrow distribution width comprised three interval ranges with different medians as follows: short interval range, 0.32 s; intermediate interval range, 0.64 s; and long interval range, 1.2 s. The wide distribution width comprised a single interval range with seven intervals having a median interval time of 0.64 s and a step size of log 0.15.
Mean coefficient of variance (CV) for trial N and N-1. Error bars show bootstrapped 95% confidence intervals. HC, healthy controls group; SZ, patients with schizophrenia group.
Mean reproduction durations of sample intervals in the narrow and wide distribution widths wherein the slope of the line provides an index for the strength of central bias. Error bars show bootstrapped 95% confidence intervals. Solid lines show best-fitting linear regressions for each range, whereas the dotted diagonal lines denote veridical (unbiased) performance. The filled circles show the values for the short interval range, the triangles show values for the intermediate interval range, the squares show values for the long interval range, and the open circles show values in the wide distribution width. HC, healthy controls group; SZ, patients with schizophrenia group. HC, healthy controls group; SZ, patients with schizophrenia group.
CV versus VE for the reproduced durations of intervals from the narrow and wide distribution widths. VE (vertical error) refers to the degree of similarity between perceived and actual timing, and CV (coefficients of variation) indicates the precision of perceived timing. Error bars show bootstrapped 95% confidence intervals. The filled circles show the values for the short interval range, the triangles show values for the intermediate interval range, the squares show values for the long interval range, and the open circles show values in the wide distribution width. HC, healthy controls group; SZ, patients with schizophrenia group; CV, coefficients of variance; VE, vertical error.
Accumulating evidence suggests that deficits in perceptual inference account for symptoms of schizophrenia. One manifestation of perceptual inference is the central bias, i.e., the tendency to put emphasis on prior experiences over actual events in perceiving incoming sensory stimuli. Using an interval reproduction task, this study aimed to determine whether patients with schizophrenia show a stronger central bias than participants without schizophrenia. In the interval reproduction task, participants were shown a cross on a screen. The cross was replaced with a Gaussian patch for a predetermined time interval, and participants were required to reproduce the interval duration by pressing and releasing the space key. We manipulated the uncertainty of prior information using different interval distributions. We found no difference in the influence of prior information on interval reproduction between patients and controls. However, patients with SZ showed a stronger central bias than healthy participants in the intermediate interval range (approximately 450 ms to 900 ms). It is possible that the patients in SZ have non-uniform deficits associated with interval range or uncertainty of prior information in perceptual inference. Further, the severity of avolition and alogia was correlated with the strength of central bias in SZ. This study provides some insights into the mechanisms underlying the association between schizophrenic symptoms and perceptual inference.
Demographic and clinical characteristics of patients.
Cognitive impairment is strongly associated with functional outcome in patients with schizophrenia but its pathophysiology remains largely unclear. Involvement of omega-3 fatty acids in the cognitive function of healthy individuals and patients with neuropsychiatric disease has received increasing attention. The aim of this study was to examine the relationship between omega-3 fatty acids with cognitive function, social function, and psychiatric symptoms in patients with schizophrenia. The subjects included 30 patients with schizophrenia or schizoaffective disorder. Psychiatric symptoms, cognitive function, and social function were assessed using the Positive and Negative Syndrome Scale, the Brief Assessment of Cognition in Schizophrenia (BACS), and the Social Functioning Scale (SFS), respectively. Blood serum omega-3 fatty acids were assessed using gas chromatography. The BACS composite score was significantly correlated with blood eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. In addition, a daily dose of antipsychotic medication was negatively and significantly correlated with the blood DHA level and with the BACS composite score. Step-wise multiple regression analyses demonstrated that the SFS score was significantly associated with the BACS composite score. Our results indicate that reduced blood omega-3 fatty acids are associated with cognitive impairment, which then impacts social functioning outcomes in schizophrenia.
Correlations between emotion-specific performance and metacognitive domains.
People with schizophrenia exhibit deficits in emotion recognition that are associated with community and social functioning. Emotion-specific performance within emotion recognition tasks has been investigated, suggesting differential patterns of recognition for positive and negative emotions. However, no study has yet examined emotion-specific performance for a higher-order social cognitive construct such as empathy. This study aimed to: 1) examine emotion-specific performance on an empathy task, and 2) elucidate associations with four metacognitive domains: self-reflectivity, understanding of others' minds, decentration, and mastery. Fifty-seven people with schizophrenia or schizoaffective disorder participated. All were administered a computerized, performance-based measure of empathy and an interview-based measure of metacognitive capacity. Results revealed that, consistent with research on facial affect recognition, participants performed significantly better when recognizing happiness in empathic stimuli than all other emotions. Results also revealed positive associations between empathic performance and metacognitive self-reflectivity, across types of emotions. Other metacognitive domains were also associated with performance, but in a less consistent manner. Together, results indicate that not all emotions are created equal – happiness is easier to recognize for those with schizophrenia, suggesting that social cognitive interventions may be more helpful if focused on recognizing negative emotions. Results also emphasize the importance of metacognitive capacity for basic and higher-order social cognitive skills.
Study 1 -sample characteristics.
Study 1 -risk perception across groups.
Study 2 -sample characteristics.
Study 2 -risk perception across groups.
Objectives It is common, among clinical and non-clinical populations alike, for paranoia and anxiety to co-occur. It has been suggested that anxiety and its related appraisal styles may contribute to development of paranoia. We aimed to evaluate different aspects of risk perception in relation to paranoia and anxiety and to identify specific aspects that may differentiate paranoia from anxiety. This paper consists of two inter-related studies. Methods Study 1 compared 30 patients with persecutory delusions, 21 patients with generalized anxiety disorder and 52 healthy controls. Study 2 compared 30 non-clinical individuals with high levels of paranoia and anxiety, 28 individuals with high anxiety only and 36 healthy controls. Within each study, the two symptomatic groups were matched on level of anxiety. Four dimensions of risk perception (i.e. likelihood, harm, controllability, and intentionality) were compared across groups, as measured by the locally validated Risk Perception Questionnaire. Results In both studies, the paranoia and the anxiety groups reported an elevated perceived likelihood of negative events than controls respectively. Only the paranoia groups reported an elevated perceived harm of neutral events than controls. In Study 2, the two at-risk groups attributed more harm and intentionality to negative events than controls. Conclusion Although perception of negative events was characteristic in anxiety (with or without paranoia), a biased perception of neutral events as risky was unique to the addition of paranoia. Implications to the transdiagnostic and continual view of psychopathology, and mechanism-based interventions were discussed.
Scatterplots and least squares regression lines depicting the relationship between SCoRS Global Rating Score (interviewer) and SOFAS score. ARMS; at-risk mental state, FES; first episode schizophrenia, CS; chronic schizophrenia, OTHERS; other psychiatric disorders with psychosis.  
Demographic and clinical data.
Comparisons of SCoRS, BACS and SOFAS data.
Cognitive function is impaired in patients with schizophrenia-spectrum disorders, even in their prodromal stages. Specifically, the assessment of cognitive abilities related to daily-living functioning, or functional capacity, is important to predict long-term outcome. In this study, we sought to determine the validity of the Schizophrenia Cognition Rating Scale (SCoRS) Japanese version, an interview-based measure of cognition relevant to functional capacity (i.e. co-primary measure). For this purpose, we examined the relationship of SCoRS scores with performance on the Brief Assessment of Cognition in Schizophrenia (BACS) Japanese version, a standard neuropsychological test battery, and the Social and Occupational Functioning Assessment Scale (SOFAS), an interview-based social function scale. Subjects for this study (n = 294) included 38 patients with first episode schizophrenia (FES), 135 with chronic schizophrenia (CS), 102 with at-risk mental state (ARMS) and 19 with other psychiatric disorders with psychosis. SCoRS scores showed a significant relationship with SOFAS scores for the entire subjects. Also, performance on the BACS was significantly correlated with SCoRS scores. These associations were also noted within each diagnosis (FES, CS, ARMS). These results indicate the utility of SCoRS as a measure of functional capacity that is associated both with cognitive function and real-world functional outcome in subjects with schizophrenia-spectrum disorders.
Categories of changes: significant, observable and no changes in the AMPS motor and process scores from admission to discharge among participants.
Factors associated with changes at discharge compared to admission in standardised AMPS motor and process scores (N = 72).
Background Impaired community functioning and functional ability are common among people with schizophrenia spectrum disorders (SSD). However, changes occurring in activities of daily life (ADL) ability through interventions provided at clinical settings have not been systematically examined in this population. Methods We retrospectively collated and analysed changes in ADL ability between admissions and discharges, measured utilising the Assessment of Motor and Process Skills (AMPS), among 72 people with SSD at a public inpatient treatment and rehabilitation facility in Western Australia. Clinical and demographic factors moderating the changes were also determined. Results The standardised AMPS motor (p = 0.0088) and process scores (p < 0.0001) improved significantly between admission and discharge. However, overall, the improvements were of small to moderate magnitude, and >60% of participants did not experience significant or meaningful changes. Furthermore, mild to moderate impairment in the AMPS standardised motor (−1.3 SD), and process (−1.6 SD) ability was present at discharge. A logistic regression analysis revealed that low admission AMPS scores and duration of illness of more than five years predicted improvement of the AMPS motor score by discharge, but only the former predicted changes in the process scores. Other demographic, clinical, and treatment-related variables did not affect the outcome of the AMPS scores. Conclusions Impairment of ADL ability is recalcitrant in schizophrenia. The improvement was modest and occurred only in a proportion of participants. However, promisingly, chronic illness, low baseline ADL ability, treatment with clozapine and presence of treatment-resistant schizophrenia did not have an adverse effect on the outcome.
Symptom dimension means of a Brazilian FEP sample at baseline and a 10-week follow-up. *Statistically significant difference between means.
analysis of outcomes, age and sex in a Brazilian FEP cohort at baseline and follow up.
Introduction: Cannabis use increases the risk of developing psychosis, and subjects with psychosis are more likely to use cannabis. However, studies on the influence of cannabis on psychotic dimensions, response to treatment, and functional outcomes showed conflicting results. Such heterogeneity may be due the inclusion of patients who were already under treatment, and lack of specificity in evaluations. We investigated whether cannabis use yields distinct symptom profiles and functionality in a cohort of antipsychotic-naïve patients at first episode of psychosis (FEP). Methods: This research is part of a prospective cohort study performed in Sao Paulo, Brazil. The baseline assessment was completed by 175 individuals, and 99 of them were reassessed in a ten-week follow up. We investigated the relationship between cannabis exposure variables (acute use, lifetime use and age at first use) and outcomes: symptom dimensions and functioning. Results: Individuals who reported acute use of cannabis had higher excitement symptoms at baseline, higher excitement and positive response rates, but no significant differences at follow-up. Additionally, more days of cannabis use in the last month predicted worse functionality and clinical impression at baseline but not at follow-up. Discussion: The acute use of cannabis influenced the clinical presentation at our FEP baseline assessment, but did not to influence symptoms or functional outcomes at 10-week follow-up. Additionally, acute cannabis users had a better response for excitement and positive symptoms. Higher excitement symptoms at presentation of FEP should raise concerns of possible acute use of cannabis. Longer follow-up times may elucidate whether the effects on functionality would be more evident later in disease development.
Overview of the development of the CAT Fidelity Scale.
Purpose Cognitive Adaptation Training (CAT) is a psychosocial intervention with demonstrated effectiveness. However, no validated fidelity instrument is available. In this study, a CAT Fidelity Scale was developed and its psychometric properties, including interrater reliability and internal consistency, were evaluated. Methods The fidelity scale was developed in a multidisciplinary collaboration between international research groups using the Delphi method. Four Delphi rounds were organized to reach consensus for the items included in the scale. To examine the psychometric properties of the scale, data from a large cluster randomized controlled trial evaluating the implementation of CAT in clinical practice was used. Fidelity assessors conducted 73 fidelity reviews at four mental health institutions in the Netherlands. Results After three Delphi rounds, consensus was reached on a 44-item CAT Fidelity Scale. After administration of the scale, 24 items were removed in round four resulting in a 20-item fidelity scale. Psychometric properties of the 20-item CAT Fidelity Scale shows a fair interrater reliability and an excellent internal consistency. Conclusions The CAT fidelity scale in its current form is useful for both research purposes as well as for individual health professionals to monitor their own adherence to the protocol. Future research needs to focus on improvement of items and formulating qualitative anchor point to the items to increase generalizability and psychometric properties of the scale. The described suggestions for improvement provide a good starting point for further development.
Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digital technology has the potential to address these limitations in order to improve cognitive and functional outcomes in recent-onset psychosis. Computer programs can be used for standardized, automated delivery of cognitive remediation training. Virtual reality provides the opportunity for learning and practicing cognitive skills in real-world scenarios within a virtual environment. Smartphone apps could be used for notification reminders for everyday tasks to compensate for cognitive difficulties. Internet-based technologies can offer psychoeducation and training materials for enhancing cognitive skills. Early findings indicate some forms of digital interventions for cognitive enhancement can be effective, with well-established evidence for human-supported computer-based cognitive remediation in recent-onset psychosis. Emerging evidence regarding virtual reality is favorable for improving social cognition. Overall, blending digital interventions with human support improves engagement and effectiveness. Despite the potential of digital interventions for enhancing cognition in recent-onset psychosis, few studies have been conducted to date. Implementation challenges affecting application of digital technologies for cognitive impairment in recent-onset psychosis are sustained engagement, clinical integration, and lack of quality in the commercial marketplace. Future opportunities lie in including motivational frameworks and behavioral change interventions, increasing service engagement in young people and lived experience involvement in digital intervention development.
Task correlations for in-person and remote administration in BD.
The MATRICS Consensus Cognitive Battery (MCCB) is a gold-standard tool for assessing cognitive functioning in individuals with severe mental illness. This study is an initial examination of the validity of remote administration of 4 MCCB tests measuring processing speed (Trail Making Test: Part A, Animal Fluency), working memory (Letter-Number Span), and verbal learning and memory (Hopkins Verbal Learning Test-Revised). We conducted analyses on individuals with bipolar disorder (BD) and schizophrenia-spectrum disorders (SCZ), as well as healthy volunteers, who were assessed in-person (BD = 80, SCZ = 116, HV = 14) vs. remotely (BD = 93, SCZ = 43, HV = 30) to determine if there were significant differences in performance based on administration format. Additional analyses tested whether remote and in-person assessment performance was similarly correlated with symptom severity, cognitive and social cognitive performance, and functional outcomes. Individuals with BD performed significantly better than those with SCZ on all MCCB subtests across administration format. Animal Fluency did not differ by administration format, but remote participants performed significantly worse on Trail Making and HVLT-R. On the Letter-Number Span task, individuals with bipolar disorder performed significantly better when participating remotely. Finally, patterns of correlations with related constructs were largely similar between administration formats. Thus, results suggest that remote administration of some of the MCCB subtests may be a valid alternative to in-person testing, but more research is necessary to determine why some tasks were affected by administration format.
Correct recall across risk groups and trials. Note. (A) Correct recall averaged across trials was significantly lower for the high-risk than other groups. (B) This nominal pattern was consistent across all five trials. Group means are shown as the heights of white diamonds (A) and bars (B), and corresponding error bars are 95% confidence intervals. (A) Medians and interquartile ranges are displayed in boxplots. Distributional information is shown as individual participant estimates (dots) and the approximated frequencies of those estimates displayed as kernel probability densities (the width of corresponding half violin plots).
Lag conditional response probabilities across risk groups. Note. Conditional response probabilities estimated from a mixed effect model. The lags only ranged from 3 to 3 because there were sparse observations at longer lags. Error bars are 95% confidence intervals. The probabilities for recalls from adjacent input positions ( 1 and 1) were significantly lower for the high-risk group than the clinical control and healthy control groups.
Risk group characteristics in free-recall and recognition tasks.
People with schizophrenia experience episodic memory impairments that have been theorized to reflect deficits in processing context (e.g., spatio-temporal features tied to a specific event). Although past research has reported episodic memory impairments in young people at-risk for schizophrenia, the extent to which these impairments reflect context processing deficits remains unknown. We addressed this gap in the literature by examining whether children and adolescents at risk for schizophrenia exhibit context processing deficits during free recall, a memory task with high contextual demands. Our sample included three groups (N = 58, 9–16 years old) varying in risk for schizophrenia:16 high-risk, unaffected first-degree relatives of patients with schizophrenia, bipolar disorder, and/or schizoaffective disorder, 22 clinical control participants with a comorbid disorder (ADHD and/or an anxiety disorder), and 20 healthy control participants. Participants first completed a free recall task and then completed a recognition memory task. Based on established theories of episodic memory, we assumed that context processing played a more pivotal role in free recall than recognition memory. Consequently, if schizophrenia risk is associated with context processing deficits, then memory impairment should be present in free recall measures that are most sensitive to context processing (i.e., recall accuracy and temporal contiguity). Consistent with this prediction, free recall accuracy and temporal contiguity were lower for the high-risk group than the healthy controls, whereas recognition memory was comparable across groups. These findings suggest that episodic memory impairments associated with schizophrenia in unaffected, first-degree relatives may reflect context processing deficits.
Group means and group comparisons for MCCB domains in adolescent patients.
Abstract Studies evaluating the cognitive impairment in schizophrenic adolescents reported a variable course following antipsychotic treatment, with improvement being associated to patients' demographic or clinical characteristics. OBJECTIVES: To examine the cognitive impairments of a Mexican sample of adolescents with schizophrenia using the MATRICS Consensus Cognitive Battery (MCCB) before and after six months of antipsychotic treatment and to determine which demographic or clinical characteristics could be associated to cognitive improvement. METHODS: A sample of 87 Mexican patients was evaluated with the MCCB. Domain scores for three age groups (12-13, 14-15 and 16-17 y.o.) were obtained at baseline, and after 3 and 6 months of treatment. The groups were compared for demographic and clinical variables (sex, school attendance, years of education, being on their first psychotic episode, duration of illness and mean dose of antipsychotic), and a logistic regression analysis was performed to determine which variables predicted larger improvement. RESULTS: The baseline performance showed scores below the standardized mean, with improvement in all domains except for social cognition; female adolescents showed a larger improvement in attention/vigilance and visual learning domains. CONCLUSIONS: We observed cognitive impairments on schizophrenic adolescents, which improved after six months of treatment in almost all domains. KEYWORDS: Attention; Cognitive dysfunction; Follow-up studies; Latin American; MATRICS; Psychotic disorders
Path diagram describing the mediating effect of dissociation on the relationship between peer victimization and hallucinatory experiences. Note. Solid black line: path coefficient is statistically significant (p b .001); dotted line: path coefficient is not significant (p N .05).
Path diagram describing the mediating effect of dissociation on the relationship between peer victimization and hallucinatory experiences.
Peer victimization increases the risk of experiencing psychotic symptoms among clinical and general populations, but the mechanism underlying this association remains unclear. Dissociation, which is related to peer victimization and hallucinatory experiences, has been demonstrated as a significant mediator in the relation between childhood victimization and hallucinatory experience among adult patients with psychosis. However, no studies have examined the mediating effect of dissociation in a general early adolescent population. We examined whether dissociation mediates the relationship between peer victimization and hallucinatory experiences among 10-year-old adolescents using a population-based cross-sectional survey of early adolescents and their main parent (Tokyo Early Adolescence Survey; N=4478). We examined the mediating effect of dissociation, as well as external locus of control and depressive symptoms, on the relationship between peer victimization and hallucinatory experiences using path analysis. The model assuming mediation effects indicated good model fit (comparative fit index = .999; root mean square error of approximation = .015). The mediation effect between peer victimization and hallucination via dissociation (standardized indirect effect = .038, p<.001) was statistically significant, whereas the mediation effects of depressive symptoms (standardized indirect effect =−.0066, p=0.318) and external locus of control (standardized indirect effect = .0024, p=0.321) were not significant. These results suggest that dissociation is a mediator in the relation between peer victimization and hallucinatory experiences in early adolescence. For appropriate intervention strategies, assessing dissociation and peer victimization as they affect hallucinatory experiences is necessary.
Mean change in neurocognitive scores from baseline to month 6 using selected tests from each cognitive domain by responder status.
Mean change in neurocognitive scores from baseline to month 6 using selected tests from each cognitive domain by use of anticholinergic medications. Cog 1: Speed of processing: Phonetic Verbal Fluency -Scaled; Cog 2: Motor speed: Finger Tapping Dominant Hand -Scaled; Cog 3: Attention/ working memory: Digit Span -Scaled; Cog 4: Visual learning & memory: Rey Complex Figure Test-Delayed Recall: Scaled; Cog 5: Verbal learning & memory: Wide Range Assessment of Memory and Learning Story-Total: Scaled; Cog 6: Executive functioning (reasoning & problem solving): Wisconsin Card Sort TestTotal Errors: Scaled; Cog 7: Social cognition: Theory of Mind-Total.
Objective To assess cognitive functioning in adolescents (12–17 years old) with schizophrenia during open-label treatment with paliperidone extended-release (pali ER). Methods In this exploratory analysis, adolescents treated with pali ER (oral, flexibly dosed, 1.5–12 mg/day) underwent cognitive assessments at baseline and month 6 using a battery of cognitive tests validated in adolescents. Correlation analysis was used to explore the relationship between cognitive assessments and clinical symptoms (Positive and Negative Syndrome Scales [PANSS] and factors) and functionality (Children Global Assessment Scale [CGAS]) at baseline and at 6 months. Results A total of 324 of 393 patients had evaluable neurocognitive data. Changes in cognition function tests from baseline to endpoint were generally small to modest, with improvement noted for most cognitive domains (motor speed, attention/working memory, verbal learning and memory, social cognition, speed of processing, executive functioning). No improvement was noted for visual learning and memory. At baseline, there were modest negative correlations between disorganized thoughts and most cognitive domains; these correlations persisted at 6 months. Other significant negative correlations at 6 months were between speed of processing and PANSS total score, positive symptoms, negative symptoms and uncontrolled hostility (p < 0.05). At 6 months, higher CGAS scores (improved functioning) positively correlated with speed of processing and executive functioning, especially among pali ER responders. Conclusions In this large sample of adolescents with schizophrenia, frank cognitive deficits across multiple domains were observed. Treatment with pali ER over 6 months did not worsen neurocognitive functioning and was possibly associated with positive improvement in certain domains.
Results of the neurocognitive test battery in TG+ and TG patients.
Introduction and methods Based on the limited research focusing on the severity of cognitive deterioration in schizophrenia with preceding toxoplasmosis, we sampled 89 demographically matched paranoid schizophrenia patients (mean age 38.97 years) with (n = 42) and without (n = 47) seroprevalence of IgG type anti T. gondii antibodies as marker of past infection. They underwent examination of verbal memory (10 words Luria test), logical memory and visual memory (BVRT), processing speed (TMT-A/DSST) and executive functions (TMT-B/verbal fluency). We compared the results of both groups, taking into account the normative values for the Bulgarian population where available. We also compared the two groups in terms of clinical severity as evidenced by positive, negative and disorganization sub-scores of the PANSS. Results While both groups were expectedly under the population norms for verbal and logical memory, seropositive patients showed significantly bigger impairment in verbal memory (Luria Smax = 72.85 vs 78.51; p = 0.029), psychomotor speed (TMT-A 50.98 s vs 44.64 s; p = 0.017), semantic verbal fluency (27.12 vs 30.02; p = 0.011) and literal verbal fluency (17.17 vs 18.78; p = 0.014) compared to the seronegative ones. In addition to that, they gave less correct answers on the BVRT (2.98 vs 4.09; p = 0.006) while making markedly more errors (13.95 vs 10.21; p = 0.002). Despite not reaching statistical significance, past toxoplasmosis was associated with higher score on the PANSS disorganization sub-scale (16.50 points vs 14.72 points) and with lower educational attainment. Conclusion Our results suggest a more profound neuropathological insult(s) resulting in greater cognitive impairment in schizophrenia cases that are exposed to T. gondii infection.
Appraisal of recent interactions.
Anticipation of future interactions.
Background Emotion recognition deficits are linked with social dysfunction in psychosis, as is inaccurate self-assessment of emotion recognition abilities. However, little is known about the link between ER and real-time social appraisals and behavior. Methods In 136 people with psychotic disorders or affective disorder with psychosis we administered a novel ecological momentary cognitive test of emotion recognition which both assesses emotion recognition ability and self-assessed performance in conjunction with ecological momentary assessment of social appraisals, motivation, and time spent alone. Hybrid mixed effects models evaluated emotion recognition's associations with social experiences. Results Better recognition ability was associated with greater pleasure and more positive appraisals of others during interactions, whereas accuracy of self-assessment of emotion recognition ability was associated with more positive appraisals of interactions and social motivation. Overestimation of emotion recognition was linked with concurrent higher social motivation yet greater desire to avoid others. Time alone was unrelated to emotion recognition ability or self-assessment of ability. Discussion Mobile emotion recognition performance was associated with appraisals of recent interactions but not behavior. Self-assessment of social cognitive performance was associated with more positive appraisals and social motivation, and may be a novel target for interventions aimed at social dysfunction.
Mean scores on symptom and functioning measures.
Correlations of prosody and facial affect recognition with functioning and symptom severity.
Task and emotion mean scores.
Studies indicate that people with schizophrenia experience deficits in their ability to accurately detect emotions, both through facial expressions and voice intonation (i.e., prosody), and that functioning and symptoms are associated with these deficits. This study aimed to examine how facial emotion and affective prosody recognition are related to functioning and symptoms in a first-episode schizophrenia sample. Further, in light of research suggesting variable emotion-specific performance in people with schizophrenia, this study explored emotion-specific performance. Participants were 49 people with a recent first episode of schizophrenia taking part in a larger RCT. Results revealed that affective prosody recognition was significantly correlated with both role and social functioning. Regarding associations with psychiatric symptoms, facial emotion recognition was significantly, negatively associated with all three positive symptom scales, whereas affective prosody recognition was significantly, negatively associated with disorganization only. Emotion-specific analyses revealed that for affective prosody, participants were most accurate in recognizing anger and least accurate for disgust. For facial emotion recognition, participants were most accurate in recognizing happiness and least accurate for fear. Taken together, results suggest that affective prosody recognition is important for social and role functioning in people with first-episode schizophrenia. Results also suggest that this group may struggle more to identify negative emotions, though additional work is needed to clarify this pattern in affective prosody and determine real-world impact on social interactions.
Baseline demographic characteristics of smoking and non-smoking participants.
Results of linear mixed-effects model assessing the association between smoking status and DFAR task.
Results of multiple regression models assessing the association between smoking status and respectively the Hinting task and the false belief score of the Picture Sequencing Task.
Introduction In patients with psychotic disorders, both tobacco smoking and deficits in social cognition and social functioning are highly prevalent. However, little is known about their relationship in psychosis. The authors sought to evaluate the multi-cross-sectional and longitudinal associations between tobacco smoking, social cognition and social functioning in a large prospective study. Methods This study was performed within the Genetic Risk and Outcome of Psychosis (GROUP) Study, a cohort study conducted in patients with non-affective psychosis (N = 1074), their unaffected siblings (N = 1047) and healthy controls (N = 549). At baseline, three years and six years of follow-up, data on tobacco smoking (using the Composite International Diagnostic Review), social cognition (emotion processing and theory of mind) and social functioning were collected. To assess associations between tobacco smoking and social cognition or social functioning, multivariate linear mixed-effects models and multiple linear regression models were used. Bonferroni correction for multiple testing was applied. Results A significant positive association was found between smoking and emotion processing (as part of social cognition) in the patient group (estimate = 1.96, SE = 0.6, p = 0.003). However, smoking was significantly negatively associated with participating in pro-social activities compared with smoking (estimate = 2.55, SE = 0.9, p = 0.004). Change in smoking behaviour was not associated with social cognition or social functioning in the longitudinal analyses. Conclusion Findings indicate that smoking patients with a non-affective psychotic disorder slightly outperformed their non-smoking peers on a task on social cognition, but participated less in pro-social activities. Commencement or cessation of smoking was not related to social cognition or functioning.
Schematic diagram of presentation sequence for a single trial during the form perception task. Participants were required to report whether a target object (either a face or a flower) was present in a visual array. ‘Object absent’ stimuli were noise arrays with a reciprocal amplitude to spatial frequency (1/f) structure, approximating visual statistics of natural scenes (Field, 1987), filtered to contain one octave of frequencies centred on 2.4 c/°, ‘Object present’ stimuli were similar noise arrays with a percentage of pixels from an object image replacing noise pixels in a portion of the image prior to filtering. All stimuli were filtered and scaled similarly, thereby ensuring similar root-mean-square contrast in ‘present’ and ‘absent’ stimuli. Participants completed four blocks of 120 trials, each containing 60 ‘object present’ and 60 ‘object absent’ trials. Stimuli were presented for an extended period of time (1000ms) and ease of detection was manipulated by systematically varying the percentage of visual noise in ‘object present’ arrays (equal numbers 55/57/60%, randomly intermixed). The location of the object within the noise was randomly assigned on each trial (equating approximately to a location within one of the 4 quadrants of the image). Participants were correctly informed that half of trials contained objects. Faces and flowers were presented in separate blocks, and participants were told prior to each block whether the block's target objects were faces or flowers. As a result of computer error, data for flower blocks were unavailable for one participant.
(A) Mean form perception sensitivity as a function of diagnostic group and image type. Sensitivity is a summary measure calculated across both face and flower stimuli. Error bars represent 95% confidence intervals. (B) Mean motion integration sensitivity as a function of diagnostic group. Error bars represent 95% confidence intervals. Data are presented on a logarithmic scale.
Motion integration task stimuli. Stimuli contain both signal dots, which move coherently, and noise dots, which move in random directions. Dots were 2mm in diameter and moved with a velocity of 10cm/s for 750ms per trial. The percentage of signal dots in the array is defined as the motion coherence level. Participants completed two blocks consisting of 50 trials each. Motion coherence level was initially set at 100% and adjusted using the adaptive QUEST algorithm in order to determine 75% correct thresholds. At 100% coherence (A) all dots move in the same direction; at 50% coherence (B) half the dots move in coherently and half move in random directions. Here, signal dots are moving to the right. Participants fixated upon a white circle 5mm in diameter and reported the direction of motion (left or right) of the coherently moving ‘signal’ dots.
Recent evidence suggests that schizophrenia is associated with impaired processing of global visual motion, but intact processing of global visual form. This project assessed whether preserved visual form detection in schizophrenia extended beyond low-level pattern discrimination to a naturalistic form-detection task. We assessed both naturalistic form detection and global motion detection in individuals with schizophrenia spectrum disorder, bipolar affective disorder, and healthy controls. Individuals with schizophrenia spectrum disorder and bipolar affective disorder were impaired relative to healthy controls on the global motion task, but not the naturalistic form-detection task. Results indicate that preservation of visual form detection in these disorders extends beyond configural forms to naturalistic object processing.
Effect sizes of sex and alcohol intake on SSTICS.
A network of early psychosis-specific intervention programs at the University of Montreal in Montreal, Quebec, Canada, conducted a longitudinal naturalistic five-year study at two Urban Early Intervention Services (EIS). In this study, 198 patients were recruited based on inclusion/exclusion criteria and agreed to participate. Our objectives were to assess the subjective cognition complaints of schizophrenic patients assessed by Subjective Scale to Investigate Cognition in Schizophrenia (SSTICS) in their first-episode psychosis (FEP) in relation to their general characteristics. We also wanted to assess whether there are sex-based differences in the subjective cognitive complaints, as well as differences in cognitive complaints among patients who use alcohol in comparison to those who are abstainers. Additionally, we wanted to monitor the changes in the subjective complaints progress for a period of five years follow-up. Our findings showed that although women expressed more cognitive complaints than men [mean (SD) SSTICS, 28.2 (13.7) for women and 24.7 (13.2) for men], this difference was not statistically significant (r = −0.190, 95 % CI, −0. 435 to 0. 097). We also found that abstainers complained more about their cognition than alcohol consumers [mean (SD) SSTICS, 27.9 (13.4) for abstainers and 23.7 (12.9) for consumers], a difference which was statistically significant (r = −0.166, 95 % CI, −0. 307 to −0.014). Our findings showed a drop in the average score of SSTICS through study follow-up time among FEP patients. In conclusion, we suggest that if we want to set up a good cognitive remediation program, it is useful to start with the patients' demands. This demand can follow the patients' complaints. Further investigations are needed in order to propose different approaches between alcohol users and abstinent patients concerning responding to their cognitive complaints.
Task presentation in the fMRI scanner for an example trial.
Neural activity in the temporoparietal junction. (a) Neural activity for decision-making between emotionally valenced faces for oxytocin administration versus placebo. After taking oxytocin, patients with schizophrenia demonstrated attenuated levels of neural activity from the bilateral precuneus along the bilateral TPJ than after taking placebo. This image is shown at an uncorrected height threshold of p < 0.001 for clusters surviving an FWE cluster-level correction of p < 0.05 (b) Contrast estimates and 90% confidence intervals for the left and right TPJ showing that neural activity is attenuated after being administered oxytocin versus placebo.
Neural activity in the amygdala. (a) Neural activity for decision-making between emotionally valenced faces for oxytocin administration versus placebo. After taking oxytocin, patients with schizophrenia demonstrated attenuated levels of neural activity within the bilateral amygdala than after taking placebo. This image is shown at an uncorrected height threshold of p < 0.001 with areas surviving an FWE peak-level correction of p < 0.05 (b) Contrast estimates and 90% confidence intervals for the left and right amygdala showing that neural activity is attenuated after being administered oxytocin versus placebo.
Performance and bias estimates.
Schizophrenia is often a severe and debilitating mental illness, frequently associated with impairments in social cognition that hinder individuals' abilities to relate to others and integrate effectively in society. Oxytocin has emerged as a putative therapeutic agent for treating social deficits in schizophrenia, but the mode of action remains unclear. This placebo-controlled crossover study aimed to elucidate the neural underpinnings of oxytocin administration in patients with schizophrenia. 20 patients with schizophrenia were examined using functional magnetic resonance imaging under oxytocin (40 IU) or placebo nasal spray. Participants performed a stochastically rewarded decision-making task that incorporated elements of social valence provided by different facial expressions, i.e. happy, angry and neutral. Oxytocin attenuated the normal bias in selecting the happy face accompanied by reduced activation in a network of brain regions that support mentalising, processing of facial emotion, salience, aversion, uncertainty and ambiguity in social stimuli, including amygdala, temporo-parietal junction, posterior cingulate cortex, precuneus and insula. These pro-social effects may contribute to the facilitation of social engagement and social interactions in patients with schizophrenia and warrant further investigation in future clinical trials for social cognitive impairments in schizophrenia.
An example four-term analogy. Response options include: A (an aquarium) -the correct response, B (a rose) -an unrelated object, C (a fishing rod) -a remote distractor related semantically, D (a shark) -a salient distractor belonging to the same semantic category and perceptually similar.
(a) The distributions of distractibility index (the difference in error rate between the analogies with and without distraction) for the groups of 30 controls vs. 30 patients of schizophrenia. (b) The respective distributions of index of vulnerability to salient distractors (the proportion of error options matching both semantically and perceptually, in all error made). Note that the latter index was computed for only the 18 controls who made at least one error (all the 30 patients made errors).
Proportional analogies between four objects (e.g., a squirrel is to tree as a golden fish is to? aquarium) were examined in 30 schizophrenia patients and 30 healthy controls. Half of the problems included distracting response options: remote semantic associates (fishing rod) and perceptually similar salient distractors (shark). Although both patients and controls performed fairly accurately on the no-distraction analogies, patients' performance in the presence of distractors was distorted, suggesting deficits in attention and cognitive control affecting complex cognition. Finally, although education, fluid intelligence, and interference resolution strongly predicted distractibility in the control group, in the schizophrenia group susceptibility to distraction was unrelated to these markers of general cognitive ability, implying an idiosyncratic nature of reasoning distortions in schizophrenia.
Impaired cognitive control, for instance increased distractibility in simple conflict tasks such as Stroop, is considered one of fundamental cognitive deficits in schizophrenia patients. Relatively less is known about patients proneness to distraction in more complex, longer-lasting cognitive tasks. We applied the four-term analogies with and without distraction to 51 schizophrenia patients in order to examine whether they display increased distractibility during analogical reasoning, and to test which kind of distractors (semantic, categorical, or perceptual) elicits their strongest distraction, as compared to 51 matched controls. We found that (a) both groups reasoned by analogy comparably well when distraction was absent; (b) in both groups distraction significantly decreased performance; (c) schizophrenia patients were significantly more distracted than the controls; (d) in both groups the semantic distractors were selected more frequently than the categorical distractors, while the perceptual distractors were virtually ignored; as well as (e) in both groups distractibility in the four-term analogies was unrelated with distractibility in the simple perceptual conflict task, suggesting that these two distraction types tap into different cognitive mechanisms. Importantly, a significantly stronger distractibility in the schizophrenia group could not be explained by their lower intelligence, because the two groups were matched on the fluid reasoning test. We conclude that during complex cognitive processing schizophrenia patients become captured by irrelevant semantic associations. The patients are also less willing to critically evaluate their responses.
Regression of positive symptoms on Hedges' g (A) and regression of negative symptoms on Hedges' g (B). Gray = SZ-All; Red = SZ-C; Blue = SZ-F. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Demographic, clinical, and cognitive variables.
Regression of education on Hedges' g (A) and regression of cognitive performance on Hedges' g (B). Gray = SZ-All; Red = SZ-C; Blue = SZ-F. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) 
Regression of age disparity on Hedges'g. Gray = SZ-All; Red = SZ-C; Blue = SZ-F. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.) 
The mismatch negativity (MMN) is an event-related potential that is consistently attenuated in people with schizophrenia. Within the predictive coding model of psychosis, MMN impairment is thought to reflect the same prediction failures that are also thought to underlie the development and crystallization of delusions and hallucinations. However, the true relationship between symptom severity and MMN impairment across studies has not yet been established. The present meta-analysis used meta-regressions to examine the relationship between MMN impairment (quantified as Hedges' g) and PANSS positive and negative symptom totals across 62 and 68 samples, respectively. Furthermore, we examined the relationship between MMN impairment and group differences in educational achievement (n = 47 samples), cognitive ability (n = 36 samples), and age (n = 86 samples). Overall, we found no significant associations between MMN impairment and symptom severity (p's > 0.50); however, we did observe a trend-level association between MMN impairment and lower education (p = 0.07) and a significant association with older age (p < 0.01) in the schizophrenia patient group. Taken together, these results challenge a simple predictive coding model of psychosis, and suggest that MMN impairment may be more closely associated with premorbid functioning than with the expression of psychotic symptoms.
Top-cited authors
Philip D Harvey
  • University of Miami Miller School of Medicine
Melissa Fisher
  • Charles Darwin University
Sophia Vinogradov
  • University of Minnesota Twin Cities
Steven Silverstein
  • University of Rochester Medical Center
Richard Rosen
  • New York Eye and Ear Infirmary