Perceptual and cognitive effects of antipsychotics in first-episode schizophrenia: The potential impact of GABA concentration in the visual cortex

Abstract

Schizophrenia is characterized by anomalous perceptual experiences (e.g., sensory irritation, inundation, and flooding) and specific alterations in visual perception. We aimed to investigate the effects of short-term antipsychotic medication on these perceptual alterations. We assessed 28 drug-naïve first episode patients with schizophrenia and 20 matched healthy controls at baseline and follow-up 8 weeks later. Contrast sensitivity was measured with steady- and pulsed-pedestal tests. Participants also received a motion coherence task, the Structured Interview for Assessing Perceptual Anomalies (SIAPA), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Proton magnetic resonance spectroscopy was used to measure gamma-aminobutyric acid (GABA) levels in the occipital cortex (GABA/total creatine [Cr] ratio). Results revealed that, comparing baseline and follow-up values, patients with schizophrenia exhibited a marked sensitivity reduction on the steady-pedestal test at low spatial frequency. Anomalous perceptual experiences were also significantly ameliorated. Antipsychotic medications had no effect on motion perception. RBANS scores showed mild improvements. At baseline, but not at follow-up, patients with schizophrenia outperformed controls on the steady-pedestal test at low spatial frequency. The dysfunction of motion perception (higher coherence threshold in patients relative to controls) was similar at both assessments. There were reduced GABA levels in schizophrenia at both assessments, which were not related to perceptual functions. These results suggest that antipsychotics dominantly affect visual contrast sensitivity and anomalous perceptual experiences. The prominent dampening effect on low spatial frequency in the steady-pedestal test might indicate the normalization of putatively overactive magnocellular retino-geniculo-cortical pathways.