How Do We Go Beyond D2 Blockers for Schizophrenia: Is the Synapse the Answer?

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Presenting Author(s): Prof. Oliver Howes, BM BCh, MRCPsych, PhD, DM, FMedSci

Date and time: 25 Mar 2023 from 09:00 to 10:00

Location: Wildrose Salon C  Floor Map

Learning Objectives

To understand:

  1. To understand the nature of synaptic brain changes in people with schizophrenia;
  2. To understand the limits of D2 blockers; 
  3. To understand potential novel treatment approaches.


This talk will consider the synaptic hypothesis of schizophrenia, reviewing post-mortem evidence, and the
recent evidence for abnormal synaptic pruning in neurons from patients. It will then review new in vivo
evidence for lower synaptic protein levels in patients. It will then consider the implications for developing
new treatments beyond D2 blockers.

Literature References

Evidence of lower synaptic vesicle density in schizophrenia.
Radhakrishnan R, Skosnik PD, Ranganathan M, Naganawa M, Toyonaga T, Finnema S, Hillmer AT, Esterlis I,
Huang Y, Nabulsi N, Carson RE, D'Souza DC.
Mol Psychiatry. 2021 Dec;26(12):7690-7698.

Synaptic density marker SV2A is reduced in schizophrenia patients and unaffected by antipsychotics in rats.
Onwordi EC, Halff EF, Whitehurst T, Mansur A, Cotel MC, Wells L, Creeney H, Bonsall D, Rogdaki M, Shatalina
E, Reis Marques T, Rabiner EA, Gunn RN, Natesan S, Vernon AC, Howes OD.
Nature Commun. 2020 Jan 14;11(1):246.

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