Longitudinal and cross-sectional investigations of long-term potentiation-like cortical plasticity in bipolar disorder type II and healthy individuals

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.

Transcranial direct current stimulation induces long-term potentiation-like plasticity in the human visual cortex

“…A total of 38 healthy participants (20 females, 18 males; age 24.2 ± 2.0 years, age range 21-31 years) were included in the analysis to be on par with studies demonstrating clear effects on VEP plasticity 5,12 . Seven additional participants were not included in the analysis: two participants suffered from a febrile infection that might have influenced VEP amplitudes, one participant was identified as being amblyopic after screening, and four participants did not complete the protocol due to technical issues.…”

“…VEP plasticity has since been established as a tool to examine patterns of disturbed neural plasticity in mental disorders. Decreased VEP plasticity in the visual cortex has been described in patients suffering from schizophrenia 8,11 , depression 5 , and bipolar disorder 7,12 . In these conditions, noninvasive brain stimulation in distinct cortical areas is increasingly applied as a biological treatment approach, potentially acting by normalizing neural plasticity 13 .…”

Impaired Potentiation of Theta Oscillations During a Visual Cortical Plasticity Paradigm in Individuals With Schizophrenia

“…Using various sensory stimulation paradigms, several studies have documented impaired LTP-like plasticity in schizophrenia ( 45 , 48 ), as well as in individuals at clinical high risk for developing a psychotic disorder (Jacob et al, under review) and in bipolar II disorder ( 49 – 51 ) and major depressive disorder ( 52 ). Previously, we showed that visual high frequency stimulation (VHFS; ~8.9 Hz) induced sustained (enduring for at least 22 min post-VHFS) potentiation of visual N1b and C1 VEP amplitudes in healthy individuals but not in patients with schizophrenia ( 45 ).…”

Childhood Adversity Is Associated With Increased KITLG Methylation in Healthy Individuals but Not in Bipolar Disorder Patients

“…In our previous genome-wide DNA methylation analysis, KIT Ligand ( KITLG ) (cg27512205) methylation was positively associated with childhood trauma and served as a mediator between childhood trauma and blunted cortisol stress reactivity in healthy controls (8). Since impaired cortisol stress reactivity is associated with bipolar disorder (9, 10), this could imply an association between KITLG methylation with bipolar disorder. Moreover, bipolar disorder patients also report higher levels of childhood adversity (11), which may lead to higher KITLG methylation if the previous findings in healthy controls were to be extrapolated to bipolar disorder patients.…”