I recently got interested in this topic because it seems like the most acute of the “mental health” conditions that we need to address before we can start moving toward a healthier brain model.
My general understanding of psychosis is that it’s an artifact of hippocampal complex function, particularly either dentate gyrus or the CA2<->CA3 portion of the transform. Looking at evidence from both hallucinogenic drugs and MRI data, we might have a couple ways to address this.
First, my understanding of the data posits that there’s actually a few discrete types of psychosis in and above duration, and those types of psychosis are directly related to specific functional modules. Acute cases usually span multiple modules and depending on whether they occur on the dorsal or ventral side they can be additive or subtractive of each other. Understanding that some people’s delusions are actually cancelling each other out is important to understand so we don’t “fix” something and make the overall “symptomology” worse.
For the purposes of this I’m going to focus on the two major categories of psychosis, “non-fixated” and “fixated”.
“Non-fixated psychosis” represents general inability to bind to external objects or concepts. This category includes general dementia presentation as well as some types of “schizophrenic psychosis”. Severe depressive disorders with “psychosis” would also fit here.
“Non-fixated psychosis” (this is a coined phrase, probably need better language) is a result of dentate gyrus hypofunction. The dentate gyrus is the filter discrimination module for the hippocampal complex, responsible for matching bits of engrams into relevant scene context. The more convoluted the dentate gyrus, the more discrete the level of discrimination.
Severe dementia and chronic psychotic episodes should all show some level of lesion or hypofunction to the dentate gyrus. This should be a diagnostic phenotype/criteria for these types of conditions.
Mechanically, there are two separate issues going on. First, the dentate gyrus filtering process is not discrete enough to properly match CA1 targets, so it’s fitting really poor engrams. This is “dissociation”. Dissociation occurs naturally as an intentional mechanic, and can be intentional. This is how daydreaming and “imagination” works. The problem is that some brains aren’t able to adjust the “filtering” level in the dentate gyrus and it gets stuck in a “low” state. Depending on the area of the dentate gyrus, this can effect single classes of function, or in severe cases all types of function.
Second, inappropriate levels of “confidence” are being generated. Usually brains handle these types of misassociations by assigning very low confidence scores, which feels like doubt or uncertainty about it. With these conditions the brain isn’t properly tagging it as low confidence and as such becomes completely indistinguishable from external stimuli information.
In clinical cases, this type of dissociation is triggering a really high valence calculation somewhere in the chain, and high valence reactions all trigger high behavioral motivation.
Looking at this a little bit more, this won’t be a full solution because the DCN’s can also induce psychotic symptomology. TMS to the Cerebellum is a whole different ball of wax unfortunately. We can use the habenula complex to gate down some salience in general, but that’s only a solution for acute cases. Not addressing chronic cases is a bad half step IMO and not that much better than the current anti-cholinergic nuking. I have no idea how to get a sense of what the ratio is of DCN induced psychosis to hippocampal complex induced psychosis, there really isn’t any clear data out there. Will have to figure out a way to infer this, maybe assuming that in studies which assert hippocampus complex correlations, an equivalent percentage are also DCN effect? I’m imagining that still leaves ~30% or so still idiopathic.
Yeah this is going to be harder than I thought. I think it’s probable we can reduce the mania of psychosis but the beliefs themselves are far too circuit level and interconnected with other processes. So far it looks like we can only accurately target the higher level state processes, which is still too broad for my comfort. Disappointing but I don’t think it’s impossible.