Schizotypy and smooth pursuit eye movements as potential endophenotypes of obsessive-compulsive disorder

Abstract

Patients with obsessive-compulsive disorder (OCD) show dysfunctions of the fronto-striatal circuitry, which imply corresponding oculomotor deficits including smooth pursuit eye movements (SPEM). However, evidence for a deficit in SPEM is inconclusive, with some studies reporting reduced velocity gain while others did not find any SPEM dysfunctions in OCD patients. Interestingly, psychosis-like traits have repeatedly been linked to both OCD and impaired SPEM. Here, we examined a large sample of n = 168 patients with OCD, n = 93 unaffected first-degree relatives and n = 171 healthy control subjects to investigate whether elevated levels of schizotypy and SPEM deficits represent potential endophenotypes of OCD. We applied a SPEM task with high demands on predictive pursuit that is more sensitive to assess executive dysfunctions than a standard task with continuous visual feedback, as episodes of target blanking put increased demands on basal ganglia and prefrontal involvement. Additionally, we examined the relation between schizotypy and SPEM performance in OCD patients and their relatives. Results indicate that OCD patients and unaffected relatives do not show deficient performance in either standard or predictive SPEM. Yet, both patients and relatives exhibited elevated levels of schizotypy, and schizotypy was significantly correlated with velocity gain during standard trials in unmedicated and depression-free OCD patients. These findings highlight the role of schizotypy as a candidate endophenotype of OCD and add to the growing evidence for predisposing personality traits in OCD. Furthermore, intact gain may represent a key characteristic that distinguishes the OCD and schizophrenia patient populations.

Recent updates of eye movement abnormalities in patients with schizophrenia: A scoping review

“…Within 30 years after Holzman's studies, the crucial finding of eye‐tracking dysfunction in SZ has been consistently reported in an extensive number of replications, 180, 194–201 where frequent small saccades were pointed out to be the distractors of eye behavior. Oculomotor control in psychiatric populations has been studied with a range of saccade paradigms, such as prosaccades (saccades to target sequences), antisaccades (saccades away from targets) and saccades to remembered targets , demanding an increase of attention 48, 55, 202–205 . Orienting toward a stimulus is reflexive, and moving one's eyes to the opposite location requires inhibitory control and maintenance of the task's instruction.…”

Along the fringes of Agency: neurodevelopmental account of the obsessive mind

“…A pathogenetic cascade partly echoing the putative one of obsessive mind has been proposed for the neurodevelopment of the psychotic mind (ie, from early childhood alterations of CD signals to distal psychotic symptoms as passivity delusions and auditory verbal hallucinations, through intermediate phenomena represented by an altered implicit SoA and anomalous self-experiences). 32,49,50 In this perspective, the hypothesis of a neurodevelopmentally determined dimensional gradient of altered sensorimotor prediction may offer a pathophysiological bridge between OCD and schizophrenia spectrum disorder, that 1) are epidemiologically associated above chance, [51][52][53] 2) present a partial polygenic overlap, 54 and 3) are clinically overlapping in terms of obsessive-compulsive features in the schizophrenia spectrum and increased schizotypy in OCD, [55][56][57][58] supporting the hypothesis of a schizo-obsessive spectrum. 59 Subjective effects of altered sensorimotor predictions, indeed, cannot be considered all-or-none phenomena 60 : the failure of sensorimotor prediction that conditions the development of both altered SoA and SoO may represent a substrate for the progressive build-out of the psychotic mind; on the contrary, milder alterations of sensorimotor predictions (and related attenuation of SoA associated with preserved SoO) may represent an enabling condition for the development of the obsessive mind.…”

Impaired Antisaccades in Obsessive-Compulsive Disorder: Evidence From Meta-Analysis and a Large Empirical Study

“…Pro- and antisaccade blocks appeared in a fixed order as the strong main effect of task (latency of antisaccades > prosaccades) is well-established throughout the literature ( 52 ). Tasks were part of a larger oculomotor battery with additional tasks, of which the results were already ( 53 , 54 ) and will be reported elsewhere.…”