The synaptic hypothesis of schizophrenia version III: a master mechanism

The synaptic hypothesis of schizophrenia has been highly influential. However, new approaches mean there has been a step-change in the evidence available, and some tenets of earlier versions are not supported by recent findings. Here, we review normal synaptic development and evidence from structural and functional imaging and post-mortem studies that this is abnormal in people at risk and with schizophrenia. We then consider the mechanism that could underlie synaptic changes and update the hypothesis. Genome-wide association studies have identified a number of schizophrenia risk variants converging on pathways regulating synaptic elimination, formation and plasticity, including complement factors and…

• W
  Wellcome

  Award: 094849/Z/10/Z
• SL
  South London and Maudsley NHS Foundation Trust
• WT
  Wellcome Trust

  Award: 094849/Z/10/Z
• MC
  Maudsley Charity

  Award: 094849/Z/10/Z
• NI
  National Institute for Health and Care Research
• KC
  King's College London
• MR
  Medical Research Council

  Awards: 094849/Z/10/Z, MC_A656_5QD30_2135, MC_U120097115