Variability in the decision process leading to saccades: A specific marker for schizophrenia?

Theleritis, Christos; Evdokimidis, Ioannis; Smyrnis, Nikolaos

doi:10.1111/psyp.12178

Cited by 17 publications

(13 citation statements)

References 62 publications

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“…These results are encouraging for future genome‐wide and follow‐up studies as they suggest that there are some relatively strong genetic effects influencing these phenotypes and they will likely be among the first to reach genome‐wide significance with the inclusion of additional individuals. It is of interest that the intra‐subject antisaccade reaction time variability is an oculomotor measure that we have repeatedly found to show different distributions between SZ cases and controls, and therefore may prove a useful SZ endophenotype [Smyrnis N et al, 2009; Theleritis C et al, 2014]. …”

Section: Discussionmentioning

confidence: 99%

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Hatzimanolis

Bhatnagar

Moes

et al. 2015

American J of Med Genetics Pt B

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Neurocognitive abilities constitute complex traits with considerable heritability. Impaired neurocognition is typically observed in schizophrenia (SZ), whereas convergent evidence has shown shared genetic determinants between neurocognition and SZ. Here, we report a genome‐wide association study (GWAS) on neuropsychological and oculomotor traits, linked to SZ, in a general population sample of healthy young males (n = 1079). Follow‐up genotyping was performed in an identically phenotyped internal sample (n = 738) and an independent cohort of young males with comparable neuropsychological measures (n = 825). Heritability estimates were determined based on genome‐wide single‐nucleotide polymorphisms (SNPs) and potential regulatory effects on gene expression were assessed in human brain. Correlations with general cognitive ability and SZ risk polygenic scores were tested utilizing meta‐analysis GWAS results by the Cognitive Genomics Consortium (COGENT) and the Psychiatric Genomics Consortium (PGC‐SZ). The GWAS results implicated biologically relevant genetic loci encoding protein targets involved in synaptic neurotransmission, although no robust individual replication was detected and thus additional validation is required. Secondary permutation‐based analysis revealed an excess of strongly associated loci among GWAS top‐ranked signals for verbal working memory (WM) and antisaccade intra‐subject reaction time variability (empirical P < 0.001), suggesting multiple true‐positive single‐SNP associations. Substantial heritability was observed for WM performance. Further, sustained attention/vigilance and WM were suggestively correlated with both COGENT and PGC‐SZ derived polygenic scores. Overall, these results imply that common genetic variation explains some of the variability in neurocognitive functioning among young adults, particularly WM, and provide supportive evidence that increased SZ genetic risk predicts neurocognitive fluctuations in the general population. © 2015 The Authors American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Hatzimanolis

Bhatnagar

Moes

et al. 2015

American J of Med Genetics Pt B

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“…In a later study RT-ISV was modelled as the variation in the decision process leading to the production of a visually guided saccade. An increase in the variation of this decision signal (thus an increase in RT-ISV) but not the increase in mean rise of the signal (corresponding to the mean RT) dissociated patients with schizophrenia from healthy controls, as well as patients with Obsessive Compulsive Disorder (Theleritis et al, 2014). These studies then suggest that increased RT-ISV, like the increase in mean RT, might represent a core…”

Section: Introductionmentioning

confidence: 89%

Modelling reaction time distribution of fast decision tasks in schizophrenia: Evidence for novel candidate endophenotypes

Fish

Toumaian

Pappa

et al. 2018

Psychiatry Research

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Increased reaction time (RT) and variability of RT in fast decision tasks is observed in patients with schizophrenia and their first degree relatives. This study used modelling of the RT distribution with the aim of identifying novel candidate endophenotypes for schizophrenia. 20 patients with schizophrenia, 15 siblings of patients and 25 healthy controls performed an oddball task of varying working memory load. Increases in mean and standard deviation (SD) of RT were observed for both patients and siblings compared to controls and they were again independent of working memory load. Ex-Gaussian modelling of the RT distribution confirmed that parameters μ, σ and τ increased significantly in patients and siblings compared to controls. The Drift Diffusion Model was applied on RT distributions. A decrease in the diffusion drift rate (v) modeling the accumulation of evidence for reaching the decision to choose one stimulus over the other, was observed in patients and siblings compared to controls. The mean time of the non-decisional sensorimotor processes (t0) and it's variance (st0) was also increased in patients and siblings compared to controls. In conclusion modeling of the RT distribution revealed novel potential cognitive endophenotypes in the quest of heritable risk factors for schizophrenia.

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“…In the present study, we analyze and report the data for five of the oculomotor tasks. The analysis for the visually guided saccade task has been reported in our previous work (Theleritis, Evdokimidis, & Smyrnis, 2014).…”

Section: General Proceduresmentioning

confidence: 99%

Shared and distinct oculomotor function deficits in schizophrenia and obsessive compulsive disorder

et al. 2016

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Detailed analysis of oculomotor function phenotypes in antisaccade, smooth eye pursuit, and active fixation tasks was performed in a sample of 44 patients with schizophrenia, 34 patients with obsessive compulsive disorder (OCD), and 45 matched healthy controls. A common pattern of performance deficits in both schizophrenia and OCD emerged including higher antisaccade error rate, increased latency for corrective antisaccades, as well as higher rates of unwanted saccades in smooth eye pursuit compared to healthy controls. This common pattern could be related to the dysfunction of a network of cognitive control that is present in both disorders, including the dorsolateral prefrontal cortex, the posterior parietal cortex, and the anterior cingulate cortex. In contrast, only patients with schizophrenia showed a specific increase for correct antisaccade mean latency and the intrasubject variability of latency for error prosaccades as well as a decrease in the gain for smooth eye pursuit, suggesting a specific deficit in saccadic motor control and the frontal eye field in schizophrenia that is not present in OCD. A specific deficit in fixation stability (increased frequency of unwanted saccades during active fixation) was observed only for OCD patients pointing to a deficit in the frontostriatal network controlling fixation. This deficit was pronounced for OCD patients receiving additional antipsychotic medication. In conclusion, oculomotor function showed shared and distinct patterns of deviance for schizophrenia and OCD pointing toward shared and specific neurobiological substrates for these psychiatric disorders.

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Variability in the decision process leading to saccades: A specific marker for schizophrenia?

Cited by 17 publications

References 62 publications

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood

Modelling reaction time distribution of fast decision tasks in schizophrenia: Evidence for novel candidate endophenotypes

Shared and distinct oculomotor function deficits in schizophrenia and obsessive compulsive disorder

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