Abstract

Visual evoked potential (VEP) plasticity is a promising assay for noninvasive examination of long-term potentiation (LTP)-like synaptic processes in the cerebral cortex. We conducted longitudinal and cross-sectional investigations of VEP plasticity in controls and individuals with bipolar disorder (BD) type II. VEP plasticity was assessed at baseline, as described previously (Elvsåshagen et al. Biol Psychiatry 2012), and 2.2 years later, at follow-up. The longitudinal sample with VEP data from both time points comprised 29 controls and 16 patients. VEP data were available from 13 additional patients at follow-up (total n = 58). VEPs were evoked by checkerboard reversals in two premodulation blocks before and six blocks after a plasticity-inducing block of prolonged (10 min) visual stimulation. VEP plasticity was computed by subtracting premodulation VEP amplitudes from postmodulation amplitudes. Saliva samples for cortisol analysis were collected immediately after awakening in the morning, 30 min later, and at 12:30 PM, at follow-up. We found reduced VEP plasticity in BD type II, that impaired plasticity was present in the euthymic phases of the illness, and that VEP plasticity correlated negatively with depression severity. There was a positive association between VEP plasticity and saliva cortisol in controls, possibly reflecting an inverted U-shaped relationship between cortisol and synaptic plasticity. VEP plasticity exhibited moderate temporal stability over a period of 2.2 years. The present study provides additional evidence for impaired LTP-like cortical plasticity in BD type II. VEP plasticity is an accessible method, which may help elucidate the pathophysiological and clinical significance of synaptic dysfunction in psychiatric disorders.

Highlights

  • Bipolar disorder (BD) type I and II affect 2–3 % of the population and can lead to marked impairments in social and occupational functioning[1,2,3]

  • The precise neural substrates for Visual evoked potential (VEP) plasticity in humans remain to be clarified, detailed studies in rodents showed that VEP increases induced by repetitive visual stimulation is long-lasting, stimulus-specific, and depends on synaptic N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and protein kinase Mζ31–33. These are all core features of long-term potentiation (LTP), which is the best characterized form of synaptic plasticity[34,35,36]. These results indicate that VEP plasticity is reduced and may reflect impairments of cortical LTP-like synaptic processes, in BD type II, major depressive disorder (MDD), and schizophrenia

  • Plasticity of the VEP is a promising assay for noninvasive examination of cortical LTP-like synaptic processes[24,25]

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Summary

Introduction

Bipolar disorder (BD) type I and II affect 2–3 % of the population and can lead to marked impairments in social and occupational functioning[1,2,3]. Preclinical studies and genetic investigations have implicated synaptic plasticity in the etiology and treatment of BD, major depressive disorder (MDD), autism spectrum disorder, and schizophrenia[13,14,15,16,17,18,19,20,21,22,23]. Despite these findings, there is a paucity of clinical evidence supporting synaptic

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