Potential Schizophrenia Medications Point to New Disease Model | Psychiatric

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We might be the last generation taking dopamine antagonists/agonist.

Which might be a good thing

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This was interesting, albeit I couldn’t understand much of what was written.

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I only skimmed throught it too.

it said something about new medicine for glutamate or gaba neurotrasmiters. something like that

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Yeah, if this approach works, I am going to read the article again when on those drugs, and see if it makes sense haha.

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New psychiatric drugs = overpromise + underdeliver

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The three new medications that reduce psychosis without blocking dopamine D2 receptors are all believed to reduce the release of dopamine and glutamate in cortico-striatal circuits (see Figure 1B). This constitutes a striking mechanistic convergence at the circuit level. We previously suggested that the neurobiology of schizophrenia evolves over the lifespan of the individual and that medications might be developed that targeted particular illness phases.

This model suggests that glutamate synaptic deficits are present prenatally and that they compromise the development and maintenance of GABA interneurons. During adolescence, the resulting deficits in GABA signaling disinhibit cortical networks, giving rise to cortical functional hyperconnectivity, noisy cortical information processing, less precise cortical representations of information, and hyperactivity of cortical projections to the striatum, contributing to the dorsal striatal dopaminergic hyperactivity that is associated with psychosis (see Figure 1A). We posit that in chronic schizophrenia, the network disinhibition triggers a homeostatic downregulation of glutamate synaptic structure and function that exacerbates the impact of programmed synaptic elimination and other mechanisms through which synaptic elimination might be accelerated in schizophrenia, such as enhanced expression of complement C4A.

I hope they are able to do something with this for the folks who already have longstanding illness. Otherwise I guess we’re waiting for the treatments to regrow synapses. Don’t get me wrong - if they show that a medication can prevent the development or progression of schizophrenia if given at a certain stage, that would still be a big step towards treating chronic schizophrenia because it would show at least one of the biological mechanisms of how the symptoms happen in the first place.

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