Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres Clinical correlates of saccadic eye movement in antipsychotic-naïve schizophrenia Aditi Subramaniam a,b,1,2 , Vijay Danivas a,b,1,2 , Sri Mahavir Agarwal a,b,1,2 , Sunil Kalmady a,b,1,2 , Venkataram Shivakumar a,b,1,2 , Anekal C. Amaresha a,b,1,2 , Anushree Bose a,b,1,2 , Janardhanan C. Narayanaswamy a,b,1,2 , Shivarama Varambally a,b,1,2 , Samuel B. Hutton c , Ganesan Venkatasubramanian a,b, ⁎ ,1,2 , Bangalore N. Gangadhar a,b,1,2 a InSTAR Program, The Schizophrenia Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India b Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India c University of Sussex, Brighton, United Kingdom ARTICLE INFO Keywords: Schizophrenia Antisaccade Prosaccade Hallucination Inhibition ABSTRACT Some aspects of saccadic performance have been found to be abnormal in chronic schizophrenia. The majority of this research has, however, been performed on patients treated with long-term antipsychotic medication. Very few studies have examined saccadic performance in antipsychotic-naïve/free patients. There are also very few studies describing the relationship between saccadic performance and clinical symptoms, particularly in anti- psychotic free patients. In this study, we compared pro and antisaccade performance in a large sample of an- tipsychotic-naïve/free schizophrenia patients (N = 45) with healthy controls (N = 57). Clinical symptoms were assessed using Scale for Assessment of Positive Symptoms (SAPS) and Negative Symptoms (SANS). In the an- tisaccade task, patients made significantly more errors, and their correct antisaccades had smaller amplitudes in comparison to healthy controls. Higher error rates were associated with increased severity of hallucinations. In the prosaccade task, patients had less accurate final eye positions, and made saccades with slower latency and reduced amplitude compared to the healthy controls. These observations in schizophrenia patients without the potential confounds of antipsychotic treatment suggest intrinsic link between saccadic deficits and schizophrenia pathogenesis. The relationship between antisaccade errors and hallucination severity supports the potential link between hallucinations and deficits in inhibitory control. 1. Introduction Oculomotor abnormalities such as increased antisaccade error rate and reduced smooth pursuit velocity gain have been consistently ob- served in schizophrenia patients (Hutton and Ettinger, 2006; O'Driscoll and Callahan, 2008), and it has been argued that the study of eye movements offers a valuable paradigm for elucidating the neurophy- siological basis of schizophrenia. The neurological circuitry underlying eye movements has been well established in primates (Goldberg and Colby, 1992), and their corresponding human counterparts have also been identified using functional imaging. Importantly, the key neural circuits involved in oculomotor control share brain regions that are implicated in schizophrenia pathogenesis (O'Driscoll et al., 2000). Moreover, eye movements provide a non-invasive yet precise and accessible means of investigating psychomotor functioning as well as neural mechanisms of higher-order cognitive processes (Gooding and Basso, 2008). Saccades are ballistic, conjugate eye movements that alter the point of fixation of the fovea. Visually guided saccades or prosaccades are generated towards a particular target in the visual field, and rely on simple sensorimotor transformations for optimal performance. Volitional saccades, such as those performed in the antisaccade task, involve higher level cognitive processes such as goal activation and spatial memory, requiring the participant to inhibit a pre-potent re- sponse of looking at a visual target, and instead generate an en- dogenously driven saccade to the mirror image location of the target (Hutton and Ettinger, 2006). Many studies have shown that prosaccade performance in http://dx.doi.org/10.1016/j.psychres.2017.10.011 Received 27 May 2016; Received in revised form 16 August 2017; Accepted 2 October 2017 ⁎ Correspondence to: Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore 560029, India. 1 www.instar-program.org. 2 www.transpsych-lab.org. E-mail address: venkat.nimhans@yahoo.com (G. Venkatasubramanian). Psychiatry Research 259 (2018) 154–159 Available online 04 October 2017 0165-1781/ © 2017 Elsevier B.V. All rights reserved. MARK