Case Report: Successful Implementation of Integrative Cognitive Remediation for Early Psychosis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMany individuals demonstrate functionally relevant impairment in neurocognition as well as social cognition early on in the course of their psychotic disorder. There is robust evidence supporting cognitive remediation as an effective treatment of cognitive dysfunction in schizophrenia. Increasingly it is accepted that earlier treatment is associated with better outcome and that it is important to systematically assess and treat cognitive dysfunction before the cognitive and functional disabilities are fully realized. However, the clinical availability of these interventions remains sparse. As we move forward with implementing evidence-based interventions into multi-component treatment for early psychosis, it is important to reflect on experience as well as evidence. This case report aims to describe the implementation of an integrative cognitive remediation program in coordinated specialty care (CSC) for early psychosis in Iceland and investigate whether the intervention is sustainable in a CSC setting. Data on the number of patients treated, facilitators trained, groups conducted, and funding was used to assess the sustainability. The results show that since initial implementation in 2016, the intervention has been routinely available as part of standard care, with over 100 patients having received the treatment. The report discusses key factors in the successful implementation of the program. Keywords: compensatory cognitive training; functional outcome; rehabilitation; schizophrenia; social cognition and interaction training.Research Fund Landspitali-The National University Hospital of Iceland 2017/2018 University of Icelan

Support for involvement of the AHI1 locus in schizophrenia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldRecently, markers in the Abelson Helper Integration Site 1 (AHI1) region were shown to be associated with schizophrenia in a family sample of Israeli-Arabs. Here, we report a study evaluating the relevance of the AHI1 region to schizophrenia in an Icelandic sample. Seven markers shown to confer risk in the previous report were typed in 608 patients diagnosed with broad schizophrenia and 1,504 controls. Odds ratios for the overtransmitted alleles in the Israeli-Arab families ranged from 1.15 to 1.29 in the Icelandic sample. After Bonferroni correction for the seven markers tested, two markers were significantly associated with schizophrenia. Thus, our results are in general agreement with the previous report, with the strongest association signal observed in a region upstream of the AHI1 gene

The sequences of 150,119 genomes in the UK Biobank

Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data(1,2). Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank(3). This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation

Schizophrenia, cognition, and aging: cognitive deficits and the relationship between test performance and aging.

To access publisher's full text version of this article click on the hyperlink belowMost measures of cognitive function decline with age during adulthood. Research indicates that people with schizophrenia experience considerable cognitive deficits. These deficits appear to become more troublesome with increasing age, but this has been debated. The aim of this research was to better understand the age related cognitive deficits of Icelandic subjects with schizophrenia in comparison to healthy individuals. Cognition of individuals 18 to 64 years of age was evaluated with 10 neuropsychological tests. People with schizophrenia performed significantly worse on all tests, as expected, indicating widespread cognitive deficits compared to healthy individuals, independent of age. Furthermore, the results suggest that people with schizophrenia follow a similar age-related trajectory of cognitive decline as healthy individuals. Overall, we conclude that the cognitive difficulties often experienced by older people with schizophrenia are better explained by lower cognitive function at the time of diagnosis than by faster cognitive decline with increasing age

Eye movement deficits in schizophrenia: investigation of a genetically homogenous Icelandic sample.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes in genetic studies of schizophrenia. The Icelandic population lends itself ideally to genetic studies due to its ethnic homogeneity and well-documented genealogy. The primary aim of this study was to assess AS and SPEM performance in a large Icelandic sample. Additional aims were to investigate the relationship between AS and SPEM task performance and to assess internal consistency, within-session performance changes and effects of SPEM target velocity on performance. METHOD: Patients with schizophrenia (N = 118) and healthy controls (N = 109) matched for age and gender underwent infrared oculographic assessment of AS and SPEM (at target velocities of 12 degrees , 24 degrees and 36 degrees /s). RESULTS: On the AS task patients displayed significantly more reflexive errors, longer latency, increased intra-individual latency variability, and reduced amplitude gain compared to controls. On the SPEM task, patients had significantly lower velocity gain and more frequent saccades during pursuit at all velocities, but group differences in velocity gain increased with increasing target velocity. Internal consistency of performance was high for all variables in both groups (Cronbach's alpha >0.77 for AS and >0.85 for SPEM) except for AS spatial error in patients (alpha = 0.38). A moderate association was found between AS and SPEM performance. By and large, patients and controls showed similar patterns of systematic within-session performance changes. CONCLUSIONS: Our findings confirm the existence of robust eye movement deficits in schizophrenia in a large sample. These measures may be studied as endophenotypes in future studies of potential schizophrenia risk genotypes in the genetically homogenous Icelandic population

Catechol-O-Methyltransferase Val158Met Polymorphism and Antisaccade Eye Movements in Schizophrenia

The catechol-O-methyltransferase (COMT) enzyme catabolizes dopamine. The val158met single nucleotide polymorphism (rs4680) in the COMT gene has received considerable attention as a candidate gene for schizophrenia as well as for frontally mediated cognitive functions. Antisaccade performance is a good measure of frontal lobe integrity. Deficits on the task are considered a trait marker for schizophrenia. The aim of this study was to investigate the association of COMT val158met polymorphism with antisaccade eye movements in schizophrenia patients and healthy controls. Schizophrenia patients (N = 105) and healthy controls (N = 95) underwent infrared oculographic assessment of antisaccades. Subjects were genotyped for COMT val158met and divided into 3 groups according to genotype (val/val, val/met, and met/met). Patients displayed significantly more reflexive errors, longer and more variable latency, and lower amplitude gain than controls (all P < 0.02). A greater number of val158 alleles was associated with shorter (P = 0.045) and less variable (P = 0.028) antisaccade latency and, nonsignificantly, with lower reflexive error rate (P = 0.056). None of these variables showed a group-by-genotype interaction (P > 0.1). There were no significant associations of genotype with measures of amplitude gain or spatial error (P > 0.2). The results suggest that COMT val158 carrier status is associated with better performance on the antisaccade task. Possible explanations of this finding are discussed

Case Report: Successful Implementation of Integrative Cognitive Remediation for Early Psychosis.

Many individuals demonstrate functionally relevant impairment in neurocognition as well as social cognition early on in the course of their psychotic disorder. There is robust evidence supporting cognitive remediation as an effective treatment of cognitive dysfunction in schizophrenia. Increasingly it is accepted that earlier treatment is associated with better outcome and that it is important to systematically assess and treat cognitive dysfunction before the cognitive and functional disabilities are fully realized. However, the clinical availability of these interventions remains sparse. As we move forward with implementing evidence-based interventions into multi-component treatment for early psychosis, it is important to reflect on experience as well as evidence. This case report aims to describe the implementation of an integrative cognitive remediation program in coordinated specialty care (CSC) for early psychosis in Iceland and investigate whether the intervention is sustainable in a CSC setting. Data on the number of patients treated, facilitators trained, groups conducted, and funding was used to assess the sustainability. The results show that since initial implementation in 2016, the intervention has been routinely available as part of standard care, with over 100 patients having received the treatment. The report discusses key factors in the successful implementation of the program

Integrative cognitive remediation for early psychosis: Results from a randomized controlled trial

To access publisher's full text version of this article click on the hyperlink belowEarly application of cognitive remediation may help prevent the development of long-term functional impairments that characterize psychotic disorders. Interventions that encompass both neurocognitive and social-cognitive training may work synergistically to bridge the gap between cognitive gains and functional outcomes in early psychosis. We integrated three cognitive remediation approaches: Neuropsychological Educational Approach to Remediation (NEAR), Compensatory Cognitive Training (CCT), and Social Cognition and Interaction Training (SCIT), and evaluated the effects on cognition, clinical symptoms, self-assessed and informant-assessed social functioning in early psychosis. A total of 49 patients diagnosed with primary psychotic disorder seeking service at an early-intervention service in Iceland were randomized to either a waiting-list control group (n = 24) or a 12-week group-based integrative cognitive remediation (n = 25). Neurocognition, social cognition, community functioning and clinical symptoms were assessed at baseline and post-treatment. The intervention group showed significant improvements in verbal memory, cognitive flexibility, working memory, ToM and a significant reduction in hostile attributions, compared to those receiving standard treatment alone, but there were no differences between groups on measures of social functioning or clinical symptoms. The intervention was well tolerated and received high treatment satisfaction ratings. Findings indicate that integrated cognitive remediation has potential to improve neurocognition and social cognition in early psychosis.Landspitali-The National University Hospital of Iceland 2016/2017 University of Iceland 2017/2018 Amor Bjornsson Memorial Fund 201

COMT val(158)met genotype and smooth pursuit eye movements in schizophrenia

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe association between the catechol-O-methyltransferase (COMT) val(158)met polymorphism (rs4680) and smooth pursuit eye movements (SPEM) was investigated in 110 schizophrenia patients and 96 controls. Patients had lower steady-state pursuit gain and made more frequent saccades than controls. Genotype was not associated with schizophrenia or SPEM, in either group or the combined sample. SPEM deficits in schizophrenia appear to be determined by genotypes other than rs4680, although the study may have lacked power to detect small effects

Neuregulin-1 genotypes and eye movements in schizophrenia

Neuregulin-1 (NRG-1) is a putative susceptibility gene for schizophrenia but the neurocognitive processes that may involve NRG-1 in schizophrenia are unknown. Deficits in antisaccade (AS) and smooth pursuit eye movements (SPEM) are promising endophenotypes, which may be associated with brain dysfunctions underlying the pathophysiology of schizophrenia. The aim of this study was to investigate the associations of NRG-1 genotypes with AS and SPEM in schizophrenia patients and healthy controls. Patients (N = 113) and controls (N = 106) were genotyped for two NRG-1 single nucleotide polymorphisms (SNPs); SNP8NRG222662, a surrogate marker for the originally described Icelandic NRG-1 risk haplotype, and SNP8NRG243177, which has recently been associated with individual differences in brain function. Subjects underwent infrared oculographic assessment of AS and SPEM. The study replicates previous findings of impaired AS and SPEM performance in schizophrenia patients (all P &lt; 0.005; all d = 0.5-1.5). SNP8NRG243177 risk allele carriers had marginally increased variability of AS spatial error (P = 0.050, d = 0.3), but there were no significant genotype effects on other eye movement variables and no significant diagnosis-by-genotype interactions. Generally, risk allele carriers (G allele for SNP8NRG222662 and T allele for SNP8NRG243177) had numerically worse performance than non-carriers on most AS and SPEM variables. The results do not suggest that NRG-1 genotype significantly affects AS and SPEM task performance. However, the power of the sample to identify small effects is limited and the possibility of a type II error must be kept in mind. Larger samples may be needed to reliably investigate such gene effects on oculomotor endophenotypes