Https://www.sciencedirect.com/topics/neuroscience/dopamine-hypothesis-of-schizophrenia

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https://www.sciencedirect.com/topics/neuroscience/dopamine-hypothesis-of-schizophrenia

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“The dopamine hypothesis of schizophrenia postulates that hyperactivity of dopamine D2 receptor neurotransmission in subcortical and limbic brain regions contributes to positive symptoms of schizophrenia, whereas negative and cognitive symptoms of the disorder can be attributed to hypofunctionality of dopamine D1 receptor neurotransmission in the prefrontal cortex (Toda & Abi-Dargham, 2007). In support of this, studies have shown an increased density of the dopamine D2 receptor in postmortem brain tissue of schizophrenia sufferers (Seeman et al., 2000). It is also reported that upregulation of D2 receptors in the caudate nucleus of patients with schizophrenia directly correlates with poorer performance in cognitive tasks involving corticostriatal pathways”

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  • Clozapine - partial agonist at D1-like receptors
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The more I read about negative symptoms the more I realize how Clozapine is the best like my psychiatrist told me. But damn these weekly blood tests and risk of low white blood cells, catching covid and die.

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Most of the article seems to make sense, but I don’t understand why upregulation of d2 receptors in the caudate nucleus leads to poorer performance in cognitive tasks. You would think it would be the opposite. Unless I am missing or misunderstanding something.

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upregulation

/ˌəpˌreɡ(y)əˈlāSH(ə)n/

noun

PHYSIOLOGY•BIOCHEMISTRY

the increase at the cellular level of the magnitude or rate of a physiological response or biochemical or process, especially of the expression of a gene.

the increase in the number or density of cell surface receptors for a physiologically active substance, causing an increase in sensitivity in response to persistent exposure.

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Not sure but I think they’re saying that too much activation of d2 receptors such as when unmedicated causes cognitive problems.

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I also read a study that says that Vraylar is better than placebo and than Abilify at combating negative symptoms.

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Yeah, that’s what it sounds like, but you also have the blockage of D1 and D5 receptors to take into account when you consider the effect of medication on cognition/negatives.

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I remember in the year before I developed sz, I had (in my personal opinion and in hindsight) a massive dopamine boost (or receptor boost) when I was doing certain things like listening to dating advice and even just being engaged at work. The problem was it felt so good I did it more and more. The rest is history.

I didn’t read the whole thing, but this theory holds water with me.

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That would cause me psychosis :joy:

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Funny thing is, 15 years later, if I have any strong feelings of everything being in it’s place and strong motivation, then within a couple of days I get positive symptoms.

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Isn’t there something to do also with d3 receptors? I haven’t done my research in a while. Anyways, I don’t see why it’s so hard to target specific receptors in our brains, but im not a neuroscientist.

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Yea Vraylar acts more on d3 than d2.

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