Ellis Chika

I'm pleased to share our review of the synaptic hypothesis of schizophrenia, out now in @molpsychiatry, with Oliver Howes, @MRC_LMS @KingsIoPPN @QMUL_WIPH We reflect on >4 decades of evidence, and use this to propose an updated synaptic hypothesis nature.com/articles/s4138…

Out in Translational Psychiatry nature.com/articles/s4139… , we examine the relationship between 2 of the major players thought to have a role in psychosis, the neuromodulator dopamine and neurotransmitter glutamate, in ppl w psychosis after antipsychotic treatment

@eosimo Thanks, Emanuele. Your work was fundamental in our thinking. I hope the write-up is going well!

Some unanswered questions: Are synaptic alterations present in unmedicated first-episode, and clinical high-risk? Are there post-synaptic deficits in vivo? Does synaptic profile differ across distinct clinical sub-types? Are synaptic and dopaminergic markers linked in vivo?

➡️Genetic variants render synapses vulnerable to pruning ➡️Stress/immune activation causes ⬆️pruning by glia ➡️This causes EI imbalance, so cog+neg symptoms; and disinhibited projections to striatum, so hyperdopaminergia, so psychosis ➡️Stress of psychosis causes more pruning

I'm pleased to share our review of the synaptic hypothesis of schizophrenia, out now in @molpsychiatry, with Oliver Howes, @MRC_LMS @KingsIoPPN @QMUL_WIPH We reflect on >4 decades of evidence, and use this to propose an updated synaptic hypothesis nature.com/articles/s4138…