Search

Speech disturbances are prevalent in psychosis. These may arise in part from executive function impairment, as research suggests that inhibition and monitoring are associated with production of cohesive discourse. However, it is not yet understood how linguistic and executive function impairments in psychosis interact with disrupted metacognition, or deficits in the ability to integrate information to form a complex sense of oneself and others and use that synthesis to respond to psychosocial challenges. Whereas discourse studies have historically employed manual hand-coding techniques, automated computational tools can characterize deep semantic structures that may be closely linked with metacognition. In the present study, we examined whether higher executive functioning promotes metacognition by way of altering linguistic cohesion. Ninety-four individuals with schizophrenia-spectrum disorders provided illness narratives and completed an executive function task battery (Delis-Kaplan Executive Function System). We assessed the narratives for linguistic cohesion (Coh-Metrix 3.0) and metacognitive capacity (Metacognition Assessment Scale – Abbreviated). Selected linguistic indices measured the frequency of connections between causal and intentional content (deep cohesion), word and theme overlap (referential cohesion), and unique word usage (lexical diversity). In path analyses using bootstrapped confidence intervals, we found that deep cohesion and lexical diversity independently mediated the relationship between executive functioning and metacognitive capacity. Findings suggest that executive control abilities support integration of mental experiences by way of increasing causal, goal-driven speech and word expression in individuals with schizophrenia. Metacognitive-based therapeutic interventions for psychosis may promote insight and recovery in part by scaffolding use of language that links ideas together.

Background Executive Functioning (EF) is an important factor for community functioning for people with severe mental illness. Cognitive remediation programs often improve EF, but do so by using multiple therapeutic techniques. Little is known regarding how individual treatment elements promote cognitive improvement. Oscillatory brain activity is a potential neurophysiological mechanism that may change as a result of targeted training on computerized exercises. The current study aimed to examine the effects of a brief EF training program on EEG and neurocognitive measures. Methods 25 people with severe mental illness were randomized to either 2 weeks of computerized EF training or control training. Training consisted of 1 h training sessions 3 times per week and 40 min of daily home training. Assessments examined EEG theta and alpha band oscillatory power during EF tasks and neurocognitive measures of EF. Results EF training resulted in greater frontal theta power and reduced posterior alpha power during computerized EF tasks than control training. Power in the alpha frequency band over frontal electrode sites did not significantly differ between the two groups as a result of training. Additionally, participants in the EF training experienced significantly greater improvement in EF ability as measured by neurocognitive tests than the control condition. Conclusions Two weeks of EF training is sufficient to produce neurophysiological and neurocognitive change. Frontal theta power and posterior alpha power may be important neurophysiological markers to consider in cognitive remediation studies, and the addition of a brief executive function training procedure to other psychosocial interventions is worth examining.

Psychotic like experiences (PLE’s) are common in the general population, particularly during adolescence, which has generated interest in how PLE’s emerge, and the extent to which they reflect either risk for, or resilience to, psychosis. The “attachment-developmental-cognitive” (ADC) model is one effort to model the effect of risk factors on PLEs. The ADC model proposes attachment insecurity as an early environmental insult that can contribute to altered neurodevelopment, increasing the likelihood of PLE’s and psychosis. In particular, early-life attachment disruptions may negatively impact numerous aspects of executive function (EF), including behavioral inhibition and emotion regulation. Yet despite the relationship of disrupted attachment to EF impairments, no studies have examined how these factors may combine to contribute to PLE’s in adolescents. Here, we examined the relative contributions of daily-life EF and attachment difficulties (avoidance and anxiety) to PLEs in typically developing youth (N = 52; ages 10–21). We found that EF deficits and high attachment insecurity both accounted for a significant proportion of the variance in PLE’s, and interacted to predict PLE manifestation. Specifically, positive PLEs were predicted by greater trouble monitoring behavioral impact, less difficulty completing tasks, greater difficulty regulating emotional reactions, greater difficulty controlling impulses and higher attachment anxiety. Negative PLEs were predicted by greater difficulty in alternating attention, transitioning across situations, and regulating emotional reactions as well as higher attachment anxiety. These results are consistent with the ADC model, providing evidence that early-life attachment disruptions may impact behavioral regulation and emotional control, which together may contribute to PLEs.

Language disorganization is an important clinical indicator of acute psychosis, yet the longitudinal course and pathogenesis are not well understood. Executive dysfunction has been suggested as a vital contributor to formal thought disorder (FTD) and may serve as a stable predictor of symptomatic risk. The paper reports a one-year prospective study of language disorganization in sixty patients with first-episode schizophrenia-spectrum disorders and investigates executive function as a predictor of persistent FTD one year after illness onset. FTD was captured using the Clinical Language Disorder Rating Scale (CLANG), which segregates language abnormalities into three empirically validated levels: syntactic, semantic, and production. After one year, patients' syntactic and semantic deficits were substantially reduced, but production impairments persisted. Patients' improvement of semantic impairment was associated with reduced disorganized symptoms while production impairment was associated with negative symptoms. We further identified two different patterns of baseline executive function predictors for both residual semantic and production impairment. We found that sustained FTD at the semantic level was predicted by both sustained attention and planning at illness onset, while residual production failure was only predicted by sustained attention. In conclusion, the present paper documents the distinct characteristics of psycholinguistic levels in FTD and isolates two different patterns of executive function predictors for persistent semantic and production language disorganization at follow-up. The findings help to disentangle FTD dimensions at different levels of language production processes, which provide clinical implications for targeting patients at risk for prolonged FTD concordant upon executive dysfunction at illness onset.

Executive function impairment is a key cognitive deficit in schizophrenia. However, traditional neuropsychological tests of executive function may not be sensitive enough to capture the everyday dysexecutive problems experienced by patients. Additionally, existing literature has been inconsistent about longitudinal changes of executive functions in schizophrenia. The present study focuses on examining the longitudinal change of executive functions in schizophrenia using the Modified Six Elements Test (MSET) that was developed based on the Supervisory Attentional System model and shown to be sensitive to everyday dysexecutive problems. In the present study, MSET performance was assessed in 31 medication-naïve first-episode schizophrenic patients at four times over a period of three years, while the 31 normal controls were assessed once. Patients demonstrated impairment in MSET as compared to controls. Importantly, the MSET impairment persisted from the medication-naïve state to clinical stabilization and the three years following the first psychotic episode though patients improved in a conventional executive test (Modified Wisconsin Card Sorting Test). Performance was not related to intelligence, educational level, symptom changes, age-of-onset, or duration of untreated psychosis. Better MSET performance at medication-naïve state predicted improvement in negative and positive symptoms over the three-year period. These findings may suggest that MSET impairment is a primary deficit in schizophrenia that occurs early in the course of the illness and remains stable irrespective of clinical state for at least three years following the first episode of schizophrenia.

Cognitive function in schizophrenia has been associated with different sociodemographic and clinical variables. Substance use disorder (SUD) history has also been associated with cognition in schizophrenia; however, contradictory results have been found regarding its influence on cognitive function. Our aim was to study the relationship between executive function and a) age, b) duration of illness, c) number of psychotic episodes, d) positive symptoms, and e) negative symptoms, in a sample of schizophrenic patients, and secondly to study whether these relationships persisted after stratification of the sample according to the presence or absence of SUD history. A final sample of 203 schizophrenic patients were evaluated for psychotic symptoms using the PANSS, and assessed using a neuropsychological battery to calculate a composite executive function score. Linear regression analyses were performed, with this executive score as the dependent variable, and age, duration of illness, number of psychotic episodes, positive PANSS score and negative PANSS score as independent variables. For the total sample, the regression model showed three variables to be significant predictors of the executive score: age (p=0.004), number of episodes (p=0.027), and PANSS negative score (p=0.003). However, once the sample was stratified, the regression model showed age (p=0.011) and number of episodes (p=0.011) to be predictor variables for the executive score in the group of schizophrenic patients with SUD history, while age (p=0.028) and PANSS negative score (p=0.006) were predictors in the group of schizophrenic patients without such history. These findings highlight the importance of considering SUD history in studies of cognitive function in schizophrenia.

Converging evidence indicates that the prefrontal cortex is critically involved in executive control and that executive dysfunction is implicated in schizophrenia. Reduced dopamine D2/D3 receptor binding potential has been reported in schizophrenia, and the correlations with neuropsychological test scores have been positive and negative for different tasks. The aim of this study was to examine the relation between dopamine D2/D3 receptor levels with frontal and temporal neurocognitive performance in schizophrenia. Resting-state 18F-fallypride positron emission tomography was performed on 20 medication-naive and 5 previously medicated for brief earlier periods patients with schizophrenia and 19 age- and sex-matched healthy volunteers. Striatal and extra-striatal dopamine D2/D3 receptor levels were quantified as binding potential using fallypride imaging. Magnetic resonance images in standard Talairach position and segmented into gray and white matter were co-registered to the fallypride images, and the AFNI stereotaxic atlas was applied. Two neuropsychological tasks known to activate frontal and temporal lobe function were chosen, specifically the Wisconsin Card Sorting Test (WCST) and the California Verbal Learning Test (CVLT). Images of the correlation coefficient between fallypride binding and WCST and CVLT performance showed a negative correlation in contrast to positive correlations in healthy volunteers. The results of this study demonstrate that lower fallypride binding potential in patients with schizophrenia may be associated with better performance. Our findings are consistent with previous studies that failed to find cognitive improvements with typical dopamine-blocking medications.

Objectives Lack of insight and neurocognitive deficits are often seen in schizophrenia patients. While there are several studies investigating the relationship between suicidal ideation, executive function and insight, there are relatively fewer investigating the triangular relationship between suicide intent, insight and cognitive competence in schizophrenia. The aim of our study was to address this issue.

article i nfo Background: The relationship between duration of untreated psychosis (DUP) and executive function (EF) in pa- tients with first-episode psychosis (FEP) is controversial. We aim to assess the influence of DUP on changes in EF over a 2-year period in subjects with early-onset FEP (first psychotic symptom before age 18) and less than 6 months of positive symptoms. Methods: A total of 66 subjects were included in the study (19 females (28.8%), mean age 16.2 ± 1.6 years). The influence of DUP on changes in EF over the 2-year follow-up (expressed as a composite score of 5 cognitive abilities: attention, working memory, cognitive flexibility, response inhibition, and problem solving) was esti- matedusingamultivariate linearregression modelafterremovingthe effectof intelligencequotientandcontrol- ling for age, gender, diagnosis, premorbid adjustment, severity of positive and negative symptoms at baseline, global functioning at baseline, and mean daily antipsychotic dosage during follow-up. Results: Mean DUP was 65.0 ± 6.9 days (95% confidence interval (CI), 51.2, 78.8). Median DUP was 47.5 days (range 2-180 days). Negative symptoms at baseline was the only variable significantly associated with EF at baseline (10.9% of explained variance (e.v. 10.9%), p = 0.007). Onlyshorter DUP (e.v. 8.7%,p = 0.013) and great- er severity of baseline negative symptoms (e.v. 10.0%, p = 0.008) were significantly associated with greater im- provement in EF. Conclusions:Inearly-onsetFEP,shorterDUPwasassociatedwithgreaterimprovementinEFovera2-yearfollow- up period.

Background Amelioration of cognitive impairment is an important treatment goal for a broad range of neuropsychiatric disorders, including schizophrenia. One critical issue in clinical trial design is the extent to which repeated exposure to cognitive tests (i.e., practice effects) may lead to improvement in performance on the cognitive tests in the absence of any true treatment effect. The current study examined the extent to which practice effects on a measure of executive function may influence the sensitivity of that task to detecting the cognitive-enhancing effects of a single acute dose of d -amphetamine in individuals with chronic schizophrenia. Methods Twenty-four men with chronic schizophrenia were randomized to receive a constant or random/matched alternate form version of a hidden maze learning measure of executive function (Groton Maze Learning Test; GMLT) on four separate occasions in one month. They also completed a measure of psychomotor speed. Using a double-blind, placebo-controlled, parallel groups design, cognitive function following administration of a single dose of d -amphetamine (20 mg p.o) or placebo was then assessed. Results The group who received the constant-pathway version of the GMLT showed a large practice effect (d = 2.05) over four practice sessions. Consequently, they did not evidence any improvement on the GMLT following d -amphetamine administration. In contrast, the group who received the random/matched alternate version of the GMLT showed a statistically significant and large effect size (d = .84) improvement on this measure. Both groups showed d -amphetamine-related improvement on a measure of psychomotor speed. Conclusions Results of this study suggest that practice effects associated with repeated exposure to a cognitive test could obscure the sensitivity of the test to detecting true treatment-related cognitive improvement.

Background The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, has reached genome-wide support as a risk factor for schizophrenia. There is initial but inconclusive evidence for a role of this variant in aspects of cognition. Methods We investigated the neurocognitive effects of the CSMD1 rs10503253 (C/A) polymorphism in a large, demographically homogeneous sample of young, healthy Greek Caucasian males (n = 1149) phenotyped for a wide range of neuropsychological measures, most of which have been shown to be reliable endophenotypes for schizophrenia. Results The risk ‘A’ allele was associated with poorer performance on measures of general cognitive ability, strategy formation, spatial and visual working memory, set shifting, target detection and planning for problem solving but not for emotional decision making. Most of these effects were dependent on risk “A” allele dose, with AA and CC homozygotes being the worse and the best respectively, while CA individuals were intermediate. Potential genotype effects in Stroop and verbal memory performance were also suggested by our dataset. Discussion These results underline the relevance of the risk “A” allele to neurocognitive functioning and suggest that its detrimental effects on cognition, may be part of the mechanism by which the CSMD1 mediates risk for schizophrenia.

In recent decade, deficits in the mechanism of Supervisory Attentional System (SAS) have become increasingly influential in explaining the nature of dysexecutive syndrome experienced by schizophrenic patients. The SAS model is characterized by having a detailed sub-classification of specific executive function components, among which semantic inhibition has been investigated using the Hayling Sentence Completion Test (HSCT). Several studies thus far have indicated that schizophrenic patients show impairment in HSCT performance. However, HSCT data concerning first-episode patients is still scarce. Besides, as previous HSCT studies were all cross-sectional in nature, they were not able to assess changes in HSCT performance over time. In order to address the paucity of knowledge about the longitudinal trajectories and correlates of semantic inhibition deficits in early schizophrenia, this paper reports a three-year prospective study of HSCT performance in medication-naive, first-episode patients with schizophrenia-spectrum disorders. HSCT performance was assessed in 34 patients at four times over a period of three years, while the 34 healthy controls were assessed once. We found that medication-naive patients demonstrated impairment in the inhibition condition in HSCT as compared to controls, but not in the initiation condition. Such HSCT impairment gradually improved in the three years following the first psychotic episode; however, HSCT performance did not predict improvement in negative or positive symptoms over the three-year period. The present findings suggest that semantic inhibition impairment is a specific deficit in schizophrenia that may require early intervention efforts, with the goal of facilitating more successful verbal communication and thereby better interpersonal functioning.

Impairments in selective components of executive function are seen in unaffected family members of patients with schizophrenia and may represent the biological expression of increased genetic risk. However no study has quantified the extent to which liability to schizophrenia overlaps genetically with that of executive dysfunction. We studied a total of 418 monozygotic and dizygotic twins, including pairs concordant and discordant for schizophrenia. Participants completed the trail making test part A and verbal fluency tasks to assess initiation, TMT part B to test mental flexibility, and the WAIS-III to assess general intellectual function. Bivariate genetic modeling was used to investigate whether selective measures of executive processing are genetically linked to schizophrenia and to quantify the genetic (i.e. heritability) and environmental contributions to their variability. Genetic influences contributed substantially to test variance for initiation and mental flexibility. Genetic factors were the main source of the phenotypic correlations between schizophrenia and these processes. Verbal fluency tasks shared a large genetic correlation with IQ whilst TMT scales did not, suggesting that they measure discreet processes, and therefore indexing discreet endophenotypes. Both verbal fluency and mental flexibility meet some of the criteria for endophenotypes, but our data suggest that mental flexibility is a purer cognitive process sharing very little common variance with general intellectual functioning. The inclusion of this mental flexibility phenotype in linkage or association analysis should improve the power to detect susceptibility genes for schizophrenia.

Background The goal of this study was to investigate differences in executive functioning between patients with early-onset and adult-onset schizophrenia spectrum psychoses at the time of first treatment. Methods Neuropsychological tests covering executive functioning domains were performed for 20 adolescents with early-onset schizophrenia (EOS) close to first treatment and 90 first episode patients with adult onset schizophrenia (AOS) in addition to 66 adolescent- and 127 adult age and gender matched healthy controls. Results Both EOS and AOS patients had significantly poorer executive performance than their age- and gender matched healthy counterparts. Both healthy adolescent controls and EOS patients had poorer executive performance than their adult counterparts. However, there were no differences in executive functioning between EOS and AOS patients after controlling for the levels of their age matched healthy control groups. Substituting EOS/AOS status with other age-at-onset thresholds had no effect. Conclusions We find the same relative levels of executive dysfunction in EOS- and AOS groups at the time of first treatment. This does not necessarily contradict previous findings of more severe dysfunction in EOS patients over time, but indicates an interaction between the disorder and the maturational processes that only can be investigated through longitudinal studies.

Neuropsychological characterization of the schizophrenia deficit syndrome is an unresolved issue. The initial assumption was that patients with deficit syndrome show more definitive impairments on tests sensitive for frontal and parietal functions compared with nondeficit patients,but recent studies failed to confirm this assumption. The fundamental question is whether a more refined delineation of executive dysfunctions is able to yield differences between deficit and nondeficit patients. To investigate this question, we implemented a factor analytic approach to explore potential differences between deficit and nondeficit patients using the Wisconsin Card Sorting Test (WCST). Our paper presents an exploratory factor analysis of the WCST on schizophrenia patients and healthy samples, and a comparison among deficit, non-deficit patients with schizophrenia and control samples using the identified factors. A total of 154 patients with schizophrenia fulfilling the criteria for the deficit syndrome, 121 nondeficit patients, and 130 healthy controls were compared. Factor analysis of the WCST variables using the principal component method resulted in a two-factor solution. Comparison of the diagnostic groups on each of the factors revealed that deficit schizophrenia patients suffer from a more severe degree of impairment on the 'General executive function' factor than nondeficit schizophrenia patients. To our knowledge this is the first study that compared patients with the deficit and non-deficit forms of schizophrenia using WCST factor analytic techniques. Our results provide an insight into the cognitive profile of schizophrenia patients with regard to WCST, which could serve as a framework for future clinical and research endeavors.

Background Impaired ability to detect and correct errors may contribute to poor cognitive and social function in schizophrenia. Objective To test the hypothesis that impairment in error monitoring contributes to impaired executive function in schizophrenia. Methods 56 schizophrenia patients and 77 healthy individuals were tested with the Penn Conditional Exclusion test (PCET), a computerised test of executive function which allowed collection of accuracy and latency performance parameters. Error monitoring was assessed by analyzing reaction times for correct (RTC) and incorrect (RTI) responses. Tests of face recognition, working memory (WM) and processing speed were also administered. Results Executive error-monitoring effort (EXER), calculated by dividing the difference between RTI and RTC by the sum of RTC and RTI, was significantly smaller in patients than controls. A regression model with the executive function (PCET total errors) as dependent variable showed independent contributions of EXER, verbal WM and spatial WM to test performance and explained 35% of the variance. EXER showed significant association with error-monitoring effort for face recognition in patients but not controls. Conclusion Impaired error-monitoring contributes to poor executive function in schizophrenia. Independent contributions of error-monitoring effort and verbal WM to executive functions may reflect distinct contributions of prefrontal and medial frontal cortical dysfunctions. Error-monitoring mechanisms in different cognitive domains may share more neural resources in schizophrenia than in healthy individuals, reflecting inefficient processing.

Background The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism has been associated with both overall schizophrenia risk and severity of negative symptoms. This study examined whether schizophrenia patients homozygous for the risk allele (T/T) exhibit greater impairment in executive function, and determined the extent to which MTHFR's effects on negative symptoms underlie this relationship. Methods 200 outpatients with chronic schizophrenia were evaluated with the Verbal Fluency Test (VFT), Wisconsin Card Sort Test (WCST), and California Verbal Learning Test (CVLT). Performance was stratified by MTHFR C667T genotype. Path analysis determined the extent to which MTHFR effects on negative symptoms mediated the relationship between genotype and cognitive measures. Results T/T subjects exhibited significantly greater deficits on the VFT and had more difficulty achieving the first category on the WCST. Genotype groups did not differ in CVLT performance. C677T effects on negative symptoms contributed to, but did not fully account for, genotype effects on VFT. Negative symptoms did not mediate WCST performance. Conclusions MTHFR C677T genotype contributes to certain executive function deficits in schizophrenia. These deficits remained significant when taking into account mediating effects of negative symptoms. Although the intermediate mechanisms for C677T effects remain uncertain, these results suggest that MTHFR-related cognitive impairment and negative symptoms reflect differing neural substrates.

Cognitive dysfunctions (as in memory, attention and executive function) have been recognized as fundamental features of schizophrenia. Executive dysfunction is a major obstacle to functional outcome, community functioning and rehabilitation success and it is crucial to assess the effects of so-called neuroleptic (NLP) medications in this domain of cognitive functioning. Risperidone, an atypical NLP, has been reported to improve executive function in schizophrenia (SZ), but there is controversy regarding these findings. The aim of the current study was to assess the differential effects of risperidone (2–6 mg) and conventional (2–40 mg haloperidol) NLPs on executive skills in 31 individuals with SZ over a 12-month period. The performance of both NLP groups was compared to the performance of 17 age- and education-matched healthy controls. In this randomized, double blind study, the Wisconsin Card Sorting Test (WCST) was administered at baseline, 3, 6, and 12 months after initiating medication. The relationship between executive functioning and the course of clinical symptoms, as assessed by the Positive and Negative Syndrome Scale (PANSS) was also investigated. Results showed that, relative to healthy controls, individuals with SZ showed marked impairment in WCST from baseline through 12 months of treatment. Also, participants under haloperidol or risperidone NLP medication performed similarly on the WCST at all assessment periods showing that risperidone and haloperidol do not differ in their effect on executive functioning. Risperidone treatment, however, was more effective in the reduction of negative symptoms. The differential efficacy of risperidone over negative symptoms and WCST performance strongly suggests that the executive impairments are to some extent the result of brain abnormalities independent of those that produce the major psychopathology manifestations seen in SZ. D 2005 Published by Elsevier B.V.

It has been suggested that lack of awareness of illness in schizophrenia may result from deficits in executive function and/or an avoidant style of coping. To examine this question, 132 persons with schizophrenia spectrum disorders were rated as either “aware,” “partially unaware” or “unaware” of: (a) their illness, (b) need for treatment and (c) consequences of disorder on the abbreviated Scale to Assess Unawareness of Mental Disorder. We next compared the performance of the aware, partially unaware and unaware groups on the “escape–avoidance” and “positive reappraisal” subtests of the Ways of Coping Questionnaire and on two tests of executive function: the Letter Number Sequencing Subtest of the WAIS III and Wisconsin Card Sorting Test. MANCOVA followed by ANCOVA and planned comparisons, controlling for age indicated that the participants who were unaware of symptoms, treatment need and consequences generally performed more poorly than the aware groups on tests of executive function. Participants unaware of symptoms also had a greater preference for positive reappraisal than aware or partially unaware participants. The participants unaware of the consequences of disorder endorsed a greater preference for escape–avoidance than the partially unaware participants. Implications for understanding the etiology of lack of awareness in schizophrenia are discussed.

The presence of memory impairment in schizophrenia has frequently been documented but much less attention has been given to the qualitative aspects of this impairment and its association to executive function. Using a cognitive-process approach, we examined memory and executive function in 25 patients who met DSM-III-R criteria for schizophrenia. Patients were matched with 25 healthy volunteers. The schizophrenic group was found to have a significant impairment in immediate memory, with relatively spared long-delay memory. Performance on verbal learning and recognition memory was similar to that of controls. Memory deficits were present irrespective of the encoding strategies used and were unrelated to chronicity. In addition, the schizophrenics performed worse than controls on tests of executive function, but the degree of impairment was greater on tests of response initiation and suppression. This pattern of performance resembled that found in patients with subcortical or frontal lesions which was supported by some significant correlations between aspects of memory and executive function. Our results suggest that in schizophrenia, specific executive functions may make a selective contribution to the pattern of memory performance in schizophrenia which is subserved by frontal and to a lesser extent hippocampal/diencephalic systems.

Transient working memory requires attention and temporary storage of information, whereas executive function working memory requires additional mental manipulation of that information. Working memory impairment is common in schizophrenia patients, but only some studies have found differential impairment in executive function working memory compared to transient working memory. We measured both types of working memory using the Digit Span forward (DF) and backward (DB) tasks in a large sample of schizophrenia patients (n=267) and normal comparison subjects (n=82); in the patients, we also examined associations between performance on the Digit Span tasks and Letter-Number Sequencing (LNS), a putative executive function working memory test. Compared to healthy subjects, the schizophrenia patients showed impairment in the medium effect size range on both DF (d=-0.55) and DB (d=-0.68). DB scores predicted LNS performance, whereas DF scores did not. Worse negative symptoms were associated with worse performance on DF, DB and LNS. These results do not reflect differential executive function working memory dysfunction in schizophrenia, but appear to support transient and executive function working memory as separable constructs.

The extent to which cognitive impairment in psychosis is related to the particular disorder or the pattern of symptoms is unclear. We examined executive function in two groups of schizophrenia patients with predominant symptoms of disorganisation (n=15) and psychomotor poverty (n=15), respectively, two groups of bipolar I disorder patients with predominant symptoms of mania (n=15) and depression (n=15), respectively, and 30 healthy controls. We predicted that the pattern of symptoms ('excess' [disorganisation/mania] or 'deficiency' [negative symptoms/depression]) would be more related to executive ability than the underlying disorder. The patient groups showed partially overlapping executive dysfunctions relative to the control group. There were no significant differences between groups with 'excess' symptoms (schizophrenia patients with thought disorder and bipolar patients with mania), or between groups with 'deficiency' symptoms (schizophrenia patients with negative symptoms and bipolar patients with depression). In contrast, differences were noted between groups with the same diagnosis: Schizophrenia patients with disorganisation were less accurate in semantic verbal fluency than those with negative symptoms; and bipolar patients with mania tended to be faster, but less accurate, in sentence completion than those with depression. A statistical comparison of the associations of 'diagnosis' and the 'excess-deficiency' dimension with executive function revealed a trend for a greater association of the latter with two measures of performance accuracy. Executive dysfunction in patients with psychotic disorders may be more related to their symptom profile than their diagnosis.

Sari Mukkala, Annamari Tuulio-Henriksson, Jouko Miettunen, Jukka Loukkola, Jennifer Barnett, Graham Murray, Erika Jaaskelainen, Pirjo Maki, Irma Moilanen, Peter Jones, Juha Veijola Department of Psychiatry, University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland; National Institute for Health and Welfare, Helsinki, Finland; Neural Ltd Oulu Finland; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Academy of Finland, Helsinki, Finland; Department of Psychology, University of Helsinki, Helsinki, Finland; Department of Child Psychiatry, University of Oulu, Oulu, Finland

Background Psychopathological symptoms and cognitive impairment are core features of patients with psychotic disorders. Executive dysfunctions are commonly observed and typically assessed using tests like the Wisconsin Card Sorting Test (WCST). However, the structure of executive deficits remains unclear, and the underlying processes may be different. This study aimed to explore and compare the network structure of WCST measures in patients with psychosis and their unaffected siblings and to empirically validate the resulting network structure of the patients. Methods The subjects were 298 patients with a DSM 5 diagnosis of a psychotic disorder and 89 of their healthy siblings. The dimensionality and network structure of the WCST were examined by means of exploratory graph analysis (EGA) and network centrality parameters. Results The WCST network structure comprised 4 dimensions: perseveration (PER), inefficient sorting (IS), failure to maintain set (FMS) and learning (LNG). The patient and sibling groups showed a similar network structure, which was reliably estimated. PER and IS showed common and strong associations with antecedent, concurrent and outcome validators. The LNG dimension was also moderately associated with these validators, but FMS did not show significant associations. Conclusions Four cognitive processes underlying WCST performance were identified by the network analysis. PER, IS and LNG were associated with and shared common antecedent, concurrent and outcome validators, while FMS was not associated with external validators. These four underlying dysfunctions might help disentangle the neurofunctional basis of executive deficits in psychosis.

International audience; Patients with schizophrenia show severe autobiographical memory impairment, thought to reflect retrieval deficits caused by executive dysfunction. However, prior research has focused exclusively on strategic (voluntary) retrieval, and ignored involuntary retrieval resulting from automatic and associative processes, involving mini- mal cognitive control. We report two studies with patients diagnosed with schizophrenia (Ns = 40 and 50 respectively) comparing their impairment in involuntary versus voluntary autobiographical memory. We use two different methodologies, not previously used in schizophrenia research: a naturalistic study involving real- life data and an experimental setup. Both studies consistently showed that involuntary and voluntary autobiographical memories were similarly impaired in schizophrenia. The absence of interaction effects between group and retrieval suggests that schizophrenic patients did not benefit from memory tasks involving little retrieval effort. These findings suggest that autobiographical memory impairment in schizophrenia are not caused by problems with self-initiated voluntary retrieval, but instead likely reflect encoding or binding deficits.

Introduction Performance in the executive function (EF) domain has been linked to symptoms and functional outcomes in psychosis. Studies have found that UHR populations have difficulty with verbal fluency, which involves multiple facets of EF. Two potentially implicated EF facets were examined to explore whether these could be dissociated in UHR populations: selection among alternatives (measured by selection costs) and retrieval from semantic memory retrieval (measured by retrieval costs). Methods A total of 45 UHR individuals and 46 healthy controls (HVs) were assessed with a verb generation task. Differences in selection cost (RT difference between high and low selection demand conditions) and retrieval cost (RT difference between high and low retrieval demand conditions) were examined and participants were also assessed for clinical symptoms. Results The UHR group showed greater selection costs relative to HVs, F (1, 91) = 4.39, p = 0.039. However, there were no group differences on retrieval cost, F (1, 91) = 0.63, p = 0.43. A positive association (r = 0.41) was found between disorganized and negative symptoms and selection costs (but not retrieval costs) in the UHR group. There was no significant association between selection costs and positive symptoms. Discussion Increased selection costs may reflect impaired performance in the neural inhibition domain of EF in the UHR population, potentially underlying a mechanistically distinct EF subdomain that affects the group's ability to efficiently select between competing options. Findings suggest that UHR individuals may exhibit impairment in selecting among alternatives, but not in retrieval from semantic memory.

Despite considerable evidence showing thalamus anatomy and connectivity abnormalities in schizophrenia, how these abnormalities are reflected in thalamus function during cognition is relatively understudied. Modulation of thalamic connectivity with the prefrontal cortex (PFC) is required for higher-order cognitive processes, which are often impaired in schizophrenia. To address this gap, we investigated how thalamus function and thalamus-PFC connectivity under different levels of cognitive demand may be disrupted in schizophrenia. Participants underwent fMRI scanning while performing an event-related two-alternative forced choice task under Single and Dual task conditions. In the Single task condition, participants responded either to a visual cue with a well-learned motor response, or an audio cue with a well-learned vocal response. In the Dual task condition, participants performed both tasks. Thalamic connectivity with task relevant regions of the PFC for each condition was measured using beta-series correlation. Individuals with schizophrenia demonstrated less modulation of both mediodorsal thalamus activation and thalamus-PFC connectivity with increased cognitive demand. In contrast, their ability to modulate PFC function during task performance was maintained. These results suggest that the pathophysiology of cognitive impairment in schizophrenia is associated with thalamus-PFC circuitry and suggests that the thalamus, along with the PFC, should be a focus of investigation.

Background In a pilot study, we assessed the potential value of deficits at the metacognitive versus the neurocognitive level of functioning for identifying adolescents with attenuated psychotic syndrome (APS). Method Twenty-two treatment-seeking adolescents with APS, 42 treatment-seeking comparisons, and 34 age-matched healthy comparisons were evaluated using the Prodromal Questionnaire, the Structured Interview for Prodromal Syndromes, and the Mood and Anxiety Symptom Questionnaire. Neurocognitive and metacognitive functioning were assessed in two non-social (verbal memory and executive functioning) and two social (facial emotion perception and theory of mind) cognitive domains. In addition to the standard neurocognitive administration of the tasks, subjects were asked to rate their confidence level on each answer and to choose whether they wanted it “counted” toward their overall task performance score on the task. Choices were rewarded. Results As hypothesized, APS among treatment-seeking adolescents was more strongly associated with impaired neurocognition than with impaired metacognition. Likewise, as hypothesized, impaired metacognition was shown to significantly improve the APS prediction beyond the contribution of impaired neurocognition alone, even after controlling for general intellectual ability, negative symptoms, social functioning, and depression. Conclusions These results suggest that metacognitive monitoring and control play a strengthening role in the association between neurocognition and APS. One possible explanation is that metacognition serves as an indicator of insight into the condition, accounting for differences in insight not explained by neurocognition alone. However, further research with larger samples that include non-treatment seeking individuals, established measures of insight, and follow-up data is required to assess this possibility.

The ability to use feedback to guide optimal decision-making is essential for goal-directed behaviour. While impairments in feedback-driven decision-making have been associated with schizophrenia and depression, this has been examined primarily in the context of binary probabilistic choice paradigms. In real-world decision-making, however, individuals must make choices when there are more than two competing options that vary in the frequency and magnitude of potential rewards and losses. Thus, the current study examined win-stay/lose-shift (WSLS) behaviour on the Iowa Gambling Task (IGT) in order to evaluate the influence of immediate rewards and losses in guiding real-world decision-making in patients with schizophrenia and major depressive disorder. Fifty-one patients with schizophrenia, 43 patients with major depressive disorder, and 51 healthy controls completed the IGT, as well as a series of clinical and cognitive measures. WSLS was assessed by quantifying trial-by-trial behaviour following rewards and losses on the IGT. Multivariate analyses of variance revealed that patients with schizophrenia demonstrated intact lose-shift behaviour, but significantly reduced win-stay rates compared to healthy controls. In contrast, no WSLS impairments emerged in the depressed group. Win-stay impairments in the schizophrenia group were significantly related to deficits in motivation and cognition. Patients with schizophrenia exhibit impaired reward-driven decision-making in the context of multiple choices with concurrent rewards and losses, and this appears to be driven by a reduced propensity for advantageous win-stay behaviour. With the importance of reward learning and decision-making in generating goal-directed behaviour, these findings suggest a potential mechanism contributing to the motivation deficits seen in schizophrenia.

We investigated the influence of anger processing on cognitive control in male schizophrenia patients presenting violent behaviors. We recruited 23 patients without and 24 patients with (SCZ + V) a history of violent behaviors, as well as 22 healthy non-violent men. Participants were administered an affective (angry-neutral faces) Go/NoGo task while undergoing functional magnetic resonance imaging. We found a reduced activation in the dorsolateral prefrontal cortex in SCZ + V patients specifically when inhibiting a response while viewing angry faces. These results show an inability of SCZ + V to recruit a core region of the (inhibitory) cognitive control network in the context of anger.

We examined the relationship between white matter microstructure in schizophrenia using diffusion tensor imaging (DTI) and cognitive improvements induced by 70 hours (~16 weeks) of cognitive training. We measured anatomical connectivity in 48 patients with schizophrenia (SZ) and 28 healthy control participants (HC) at baseline, and then examined the relationship between anatomical connectivity at baseline and training-induced cognitive gains in 30 SZ who performed diffusion imaging after completing 70 hours of training. Compared with healthy control participants, individuals with schizophrenia showed reduced white matter integrity at baseline, as indexed by fractional anisotropy metrics, in bilateral posterior corona radiata, bilateral retrolenticular internal capsules, bilateral posterior thalamic radiation, left anterior corona radiata, left superior longitudinal fasciculus, left sagittal stratum, right cerebral peduncle and the genu and splenium of the corpus callosum. After training, schizophrenia participants showed significant gains in attention/vigilance, speed of processing, verbal learning, visual learning and executive functioning. White matter integrity within the right fronto-occipital fasciculus predicted training-induced improvements in attention/vigilance, while white matter integrity within the right corticospinal tract and bilateral medial lemnisci predicted cognitive training-induced improvements in executive functioning, areas that did not show white matter tract deficits at baseline. These findings suggest that preserved white matter integrity connecting long-range prefrontal-thalamic-sensorimotor areas may be an important determinant for training-induced neurocognitive plasticity.

Subtle social cognitive deficits in unaffected relatives of schizophrenia patients have received increasing attention over the last few years, supporting their potential endophenotypic role for this disorder. The current study assessed non-psychotic first-degree relatives' performance on a multidimensional measure of emotional intelligence (EI): the Mayer–Salovey–Caruso Emotional Intelligence Test 2.0 (MSCEIT). Endorsed by the National Institute of Mental Health, the MSCEIT is a valid and reliable instrument for detecting emotion-processing deficits among schizophrenia patients and people high in schizotypy. Method : Thirty-seven first-degree relatives, 37 schizophrenia outpatients and 37 healthy controls completed the MSCEIT, which comprises eight subscales aimed to assess the four branches of EI: Identifying, Facilitating, Understanding and Managing Emotions. Potential associations with cognitive function and schizotypy levels, measured with the Schizotypal Personality Questionnaire–Brief, were further evaluated. Results : Relatives had significantly lower MSCEIT total scores than controls and also significantly lower scores on the Identifying emotions branch. Nevertheless, schizophrenia patients still had the poorest global EI performance. The strongest positive correlations were found in relatives and controls with measures of executive function, processing speed and general intelligence. A higher level of schizotypy correlated significantly with lower MSCEIT scores among controls, but not among relatives. Conclusions : Contrary to expectations in the general population, the current study observed subtle EI impairment in non-psychotic first-degree relatives of schizophrenia patients. These findings support the hypothesis that these EI deficiencies may be potential endophenotypes located between the clinical phenotype and the genetic predisposition for schizophrenia.

Schizoaffective patients can have neurocognitive deficits and default mode network dysfunction while being acutely ill. It remains unclear to what extent these abnormalities persist when they go into clinical remission. Memory and executive function were tested in 22 acutely ill schizoaffective patients; they also underwent fMRI scanning during performance of the n-back working memory test. The same measures were obtained after they had been in remission for ≥ 2 months. Twenty-two matched healthy individuals were also examined. In clinical remission, schizomanic patients showed an improvement of memory but not of executive function, while schizodepressive patients did not change in either domain. All schizoaffective patients in clinical remission showed memory and executive impairment compared to the controls. On fMRI, acutely ill schizomanic patients had reversible frontal hypo-activation when compared to clinical remission, while activation patterns in ill and remitted schizodepressive patients were similar. The whole group of schizoaffective patients in clinical remission showed a failure of de-activation in the medial frontal gyrus compared to the healthy controls. There was evidence for memory improvement and state dependent changes in activation in schizomanic patients across relapse and remission. Medial frontal failure of de-activation in remitted schizoaffective patients, which probably reflects default mode network dysfunction, appears to be a state independent feature of the illness.

Insight is impaired in most patients with psychosis and has been associated with poorer prognosis. The exact neural basis of impaired insight is still unknown, but it may involve disrupted prefrontal neural connectivity. Numerous studies have indeed found white matter (WM) abnormalities in psychosis. The association between prefrontal WM abnormalities and insight has not been studied yet by means of proton magnetic resonance spectroscopy (H-1-MRS). H-1-MRS can be used to measure N-acetylaspartate (NAA), which is considered to be a marker of neuronal integrity. We measured insight with the Birchwood Insight Scale (BIS) as well as item G12 of the Positive and Negative Syndrome Scale (PANSS) in 88 patients with psychosis. Prefrontal WM concentrations of NAA and ratios of NAA to creatine (Cr) were assessed with H-1-MRS. Nonparametric partial correlational analyses were conducted between NAA concentrations and insight controlling for illness duration, standardized antipsychotic dose, symptom scores, voxel grey matter content and voxel cerebrospinal fluid content. We found a significant correlation between reduced NAA/Cr ratios and poorer insight as measured with the BIS, which remained significant after additional correction for full width at half maximum, signal/noise and age. This is the first study reporting a relationship between lower prefrontal concentrations of a marker of neuronal integrity and impaired insight, providing further evidence that prefrontal pathology may play an important role in impaired insight in psychosis. This may be explained by the involvement of the prefrontal cortex in several executive and metacognitive functions, such as cognitive flexibility and perspective taking. (C) 2016 Elsevier B.V. All rights reserved.

Background It has been suggested that the effect of cognitive remediation (CR) on functioning is mediated by the improvement in neurocognitive domains; especially executive function. However, the correlations are generally moderate and this has prompted the search for other mediators including negative symptoms (NS). Aims To investigate whether the effect of CR on functioning could be mediated by executive function and/or NS. Method In a previous study, 62 outpatients with schizophrenia were randomized to 32 group sessions of REPYFLEC CR or leisure activities. Functioning (Life Skills Profile; LSP), NS (PANSS) and executive function (Behavioral Assessment of the Dysexecutive Syndrome; BADS) were measured at baseline and post-therapy. To assess how the effect of REPYFLEC CR is expressed in functioning at post-treatment, an autoregressive mediation model was employed. Results There was a significant effect of the REPYFLEC CR compared with the control group in improving BADS total score and PANSS NS. There was also a significant association between NS and functioning while executive function was not significantly related to functioning. Finally, there was a significant intervention effect on functioning mediated by NS but not by executive function. Conclusion It is apparent that improving executive function does not lead directly to improved functional outcome and that NS might be closely linked to functioning in the context of our study.

Impaired insight into illness is a common but poorly understood phenomenon in schizophrenia. Several studies in midlife adults with schizophrenia have reported an association between impaired insight and illness severity, executive dysfunction, premorbid intellectual function, and to a lesser degree attention. Aging is associated with a decline in attention and executive function. Thus, the relationship between cognition and insight is expected to differ between younger and older adults with schizophrenia. This study assessed this relationship among 50 patients with schizophrenia 60 years and older. Insight was explained by illness severity (16.2% of the variance) and premorbid intellectual function (23.9% of the variance), but not by attention or executive function. Our findings suggest that the predictors of insight in schizophrenia differ early and later in life. In particular, insight's association with attention and executive function observed in younger patients is attenuated by age-related changes in cognition. In contrast, premorbid intellectual function continues to be a strong predictor of insight in late life, which highlights the need to better understand and enhance cognitive function early in the course of schizophrenia.