Meta-analysis of cognitive performance in drug-naïve patients with schizophrenia

Fatouros‐Bergman, Helena; Červenka, Simon; Flyckt, Lena; Edman, Gunnar; Farde, Lars

doi:10.1016/j.schres.2014.06.034

Cited by 212 publications

(149 citation statements)

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“…Broad executive function impairments are also seen in schizophrenia, in which real-world cognitive difficulties are pervasive (e.g. Fatouros-Bergman et al, 2014). But OCD is not thought to simply be a forme fruste of schizophrenia; clinically, the difficulties patients have in cognitively demanding situations are quite distinct in the two disorders, at least in typical cases.…”

Section: The Paradox Of Broad Executive Function Deficits In Ocdmentioning

confidence: 99%

Cognitive inflexibility in Obsessive-Compulsive Disorder

Gruner¹,

2017

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Obsessive-Compulsive Disorder (OCD) is characterized by maladaptive patterns of repetitive, inflexible cognition and behavior that suggest a lack of cognitive flexibility. Consistent with this clinical observation, many neurocognitive studies suggest behavioral and neurobiological abnormalities in cognitive flexibility in individuals with OCD. Meta-analytic reviews support a pattern of cognitive inflexibility, with effect sizes generally in the medium range. Heterogeneity in assessments and the way underlying constructs have been operationalized point to the need for better standardization across studies, as well as more refined overarching models of cognitive flexibility and executive function. Neuropsychological assessments of cognitive flexibility include measures of attentional set shifting, reversal and alternation, cued task switching paradigms, cognitive control measures such as the Trail-Making and Stroop tasks, and several measures of motor inhibition. Differences in the cognitive constructs and neural substrates associated with these measures suggest that performance within these different domains should be examined separately. Additional factors, such as the number of consistent trials prior to a shift and whether a shift is explicitly signaled or must be inferred from a change in reward contingencies, may influence performance, and thus mask or accentuate deficits. Several studies have described abnormalities in neural activation in the absence of differences in behavioral performance, suggesting that our behavioral probes may not be adequately sensitive, but also offering important insights into potential compensatory processes. The fact that deficits of moderate effect size are seen across a broad range of classic neuropsychological tests in OCD presents a conceptual challenge, as clinical symptomatology suggests greater specificity. Traditional cognitive probes may not be sufficient to delineate specific domains of deficit in this and other neuropsychiatric disorders; a new generation of behavioral tasks that test more specific underlying constructs, supplemented by neuroimaging to provide greater insight into the underlying processes, may be needed.

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Section: The Paradox Of Broad Executive Function Deficits In Ocdmentioning

confidence: 99%

Cognitive inflexibility in Obsessive-Compulsive Disorder

Gruner¹,

2017

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“…Impaired working memory reduces the capacity of schizophrenia patients to maintain information across a delay and protect it from interference (Fleming et al 1995;Kim et al 2004;Fatouros-Bergman et al 2014). Due to their high prevalence, robustness, and severity, working memory deficits have been proposed as a core component to the diagnosis (Mesholam-Gately et al 2009).…”

Section: The Measurement and Treatment Research To Improve Cognition mentioning

confidence: 99%

“…Working memory impairments are robust and highly prevalent among patients (Mesholam-Gately et al 2009). The severity of impairment is highlighted by the collection of working memory vulnerabilities, including the inability to maintain information across a delay or protect it from interference (Fleming et al 1995;Kim et al 2004;Fatouros-Bergman et al 2014). …”

Section: Introductionmentioning

confidence: 99%

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

et al. 2016

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The cognitive symptoms observed in schizophrenia are highly prevalent and predictive of patient functional outcome but are not usually alleviated by conventional antipsychotics. In a recent pilot study, sodium nitroprusside (SNP), a nitric oxide donor, was identified as a promising adjunct treatment to reduce the working memory impairments experienced by schizophrenia patients.Adjunctive SNP has also been reported to decrease the positive and negative symptoms experienced by patients for weeks following a single administration. The mechanisms underlying these changes and the areas of cognition affected remain largely unknown.Therefore, it is of interest to examine the effects of SNP using a rodent model of schizophrenia that has demonstrated predictive validity. The aim of the present experiment was to explore the effects of SNP on the acute MK-801 rodent model of schizophrenia using a highly translatable task in order to establish its validity. Working memory and pattern separation were measured using the trial-unique, delayed nonmatching-to-location (TUNL) task in touchscreen-equipped operant conditioning chambers. Acute MK-801 administration 25 minutes prior to task initiation impaired both areas of cognition. When SNP and MK-801 were administered within 5 minutes of each other, no interaction was observed. Interestingly, SNP improved performance on trials with difficult to discriminate patterns (p=0.058). Previous rodent studies using the ketamine model of schizophrenia and the novel object preference task observed a preventative effect of SNP administration. When we administered SNP nearly 4 hours prior to MK-801, no cognitive improvements were observed. Our results suggest that SNP may have intrinsic cognitive enhancing properties but is not capable of reducing MK-801-induced working memory and pattern separation impairments in the TUNL task. This study failed to mirror the results of the human pilot study that observed improved working memory following SNP administration.iii Further, it did not replicate previous animal studies using ketamine. Ultimately, the findings suggest that the effects of MK-801 in the TUNL task may not hold the predictive validity needed for its use in the study of SNP. In order to advance the understanding of SNP, future studies should investigate other translatable paradigms to establish validity. iv ACKNOWLDGEMENTSFirst and foremost, I would like to thank my supervisor Dr. John Howland, for his guidance and encouragement over the past three years. He believed in my abilities before I had proven them to myself and pushed me to be the best scientist and student I could be. John has provided me with countless opportunities to grow as a researcher and selflessly helped me make decisions about my future. I would not be where I am today without him and will always be grateful to have had such an incredible mentor in my life.I would like to thank my committee members, Dr.

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“…As Gottesman and Gould6 defined, endophenotypes measure components unseen by the unaided eye along the pathway between disease and distal genotype, which may provide a more reliable index of liability than disorder itself. Previous literature reports that individuals with schizophrenia, compared with normal controls, have deficits in verbal memory, speed of cognitive processing, working memory, and verbal fluency789.…”

mentioning

confidence: 99%

Performance of Verbal Fluency as an Endophenotype in Patients with Familial versus Sporadic Schizophrenia and Their Parents

Liang

Deng

Wang

et al. 2016

Sci Rep

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What’s the neurocognitive deficit as an endophenotype to familial schizophrenia? Here, we investigate the neurocognitive endophenotype in first-episode patients with familial schizophrenia (FS) and sporadic schizophrenia (SS), and their parents. 98 FS patients and their 105 parents; 190 SS patients and their 207 parents; 195 controls matched with patients, and 190 controls matched with the patients’ parents, were assessed with the short version of the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC), the immediate and delayed logical memory tests from the Wechsler Memory Scale-Revised in China (WMS-RC), the Verbal Fluency Test (VFT), the Trail Making Test Parts A and B-Modified (TMA, TMB-M), and the Modified Wisconsin Card Sorting Test (WCST-M). The results showed that with age, gender, and education as covariates, after controlling for false discovery rates, the FS group and their parent group performed worse than the SS group and their parent group on VFT. No significant differences were found for other neurocognitive tests between the FS and SS patient groups, and their respective parent groups. Our findings suggest the patients with familial and sporadic schizophrenia and their respective parent groups may have a different genetic predisposition in relation to a cognitive endophenotype.

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Meta-analysis of cognitive performance in drug-naïve patients with schizophrenia

Cited by 212 publications

References 50 publications

Cognitive inflexibility in Obsessive-Compulsive Disorder

Cognitive inflexibility in Obsessive-Compulsive Disorder

MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside

Performance of Verbal Fluency as an Endophenotype in Patients with Familial versus Sporadic Schizophrenia and Their Parents

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