Evidence for reduced long-term potentiation-like visual cortical plasticity in schizophrenia and bipolar disorder

Valstad, M.; Roelfs, D.; Slapo, N. B.; Timpe, C. M. F.; Rai, A.; Matziorinis, A. M.; Beck, D.; Richard, G.; Saether, L. S.; Haatveit, B.; Nordvik, J. E.; Hatlestad-Hall, C.; Einevoll, G. T.; Mäki-Marttunen, T.; Haram, M.; Ueland, T.; Lagerberg, T. V.; Steen, N. E.; Melle, I.; Westlye, L. T.; Jönsson, E. G.; Andreassen, O. A.; Moberget, T.; Elvsashagen, T.

doi:10.1101/2020.06.06.128926

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bioRxiv · 10.1101/2020.06.06.128926

Evidence for reduced long-term potentiation-like visual cortical plasticity in schizophrenia and bipolar disorder

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Abstract

BackgroundSeveral lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. MethodsWe measured the VEP of patients with SZ spectrum disorders (n=31), BDI (n=34), BDII (n=33), and other BD spectrum disorders (n=2), and age-matched healthy control participants (n=200) before and after prolonged visual stimulation. ResultsCompared to healthy controls, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum ({chi}2=35.1, p=3.1x10-9) and BD spectrum ({chi}2=7.0, p=8.2x10-3), including BDI ({chi}2=6.4, p=0.012), but not BDII ({chi}2=2.2, p=0.14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients ({chi}2=14.2, p=1.7x10-4). The reduction in N1b modulation was related to PANSS total scores ({chi}2=10.8, p=1.0x10-3), and nominally to number of psychotic episodes ({chi}2=4.9, p=0.027). Conclusions. These results suggest that LTP-like plasticity is impaired in SZ and BDI, but not BDII, and related to psychotic symptom severity. Adding to previous genetic, pharmacological, and anatomical evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

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Valstad, M., Roelfs, D., Slapo, N. B., Timpe, C. M. F., Rai, A., Matziorinis, A. M., Beck, D., Richard, G., Saether, L. S., Haatveit, B., Nordvik, J. E., Hatlestad-Hall, C., Einevoll, G. T., Mäki-Marttunen, T., Haram, M., Ueland, T., Lagerberg, T. V., Steen, N. E., Melle, I., Westlye, L. T., Jönsson, E. G., Andreassen, O. A., Moberget, T., Elvsashagen, T.. 2020-06-08. Evidence for reduced long-term potentiation-like visual cortical plasticity in schizophrenia and bipolar disorder. https://doi.org/10.1101/2020.06.06.128926

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