NMDA Hyperfunction in Autism

[sekio]

Nasty side effects of memantine? Like what? I found it was even milder than DXM, and I was taking it at FAR above the recommended dose (hundreds of mgs)

 

[Flynnal]

I heard that it sometimes caused a bit of depersonalisation. Something I'd hope wouldn't happen to me.

How was memantine for you?

 

[dopamimetic]

Nasty side effects for many? Sounds like a different drug, honestly afaik most people find memantine does very little and if it's just cause younger people tend to require more than those 20mg. But really, dissociation, insomnia and euphoria is all you get.. maybe some initial headache. Despersonalisation is different from dissociation, I don't think you'd get that one.

Alcohol doesn't work for me and there is this theory of too much GABA inhibition too which would fit in that benzos make me just sleepy and stupid (of course, they are anxiolytics but fail in every other relation) while dissociatives are effective anxiolytics too and normalize senses, thinking and memory to some degree.. maybe most disturbing for me is memory imbalance. I tend to always, always race about things in the past that I and nobody ever could change without a time machine. Why spend energy to those things? I just can't stop it. Keeps you from being normally social too. Block some of my NMDA receptors and it's just gone.

Don't have any autism diagnosis tho, I gave up at psychiatry some time ago when they decided to label me paranoid schizophrenic again. Friend who is diagnosed by Mrs. Asperger personally heavily suspects I am too tho.

 

[Wilson Wilson]

I supposedly have AS. When I was 18, and going out to a party with my stepsisters, cousins, sisters, etc, I had a couple of beers to get started, and my sisters told me that I acted normal for the first time in my life. Normal.

Was it the NMDAR antagonism that caused this semblance of "normality" in my AS brain? I would never know, as I've done alcohol later on, and yes, it certainly made life a whole lot easier to deal with, but I decided I wasn't going down the alcoholic path where I'd be drinking escalating doses of this poison just to feel or seemingly act normal.

Then I saw dissociatives like ketamine, memantine, methoxetamine, and wanted to try them out, especially the memantine. But the doctor indicated that he wasn't comfortable putting me on memantine because of the nasty side effects for many people who are taking it. Not sure what a safe dose of memantine is, but I've done DXM 30mg and it made me feel a little weird.

It would be interesting to see how you react to ketamine, that'd give you a reasonable idea. Tiny bumps of ketamine every week or so can do wonders for anxiety and depression, which includes social anxiety, so it can certainly help in the respect of "acting normal" if your brain responds well to it.

I used to resort to popping benzos to ease social situations but like you it wasn't long until I worked out relying on them too much was a bad idea and I avoid frequent use now. But those GABAergic effects do help me socialise more fluidly.

Alcohol helps if I only drink enough to get a bit of a buzz on. I don't enjoy actually getting drunk at all.

Weed seems to work rather well as a less toxic social lubricant for me and that's what I tend to favour now.

 

[dopamimetic]

Another paper just found (older though, from 2012).

Psychosis and autism as diametrical disorders of the social brain

Abstract: Autistic-spectrum conditions and psychotic-spectrum conditions (mainly schizophrenia, bipolar disorder, and major depression) represent two major suites of disorders of human cognition, affect, and behavior that involve altered development and function of the social brain. We describe evidence that a large set of phenotypic traits exhibit diametrically opposite phenotypes in autistic-spectrum versus psychotic-spectrum conditions, with a focus on schizophrenia. This suite of traits is inter-correlated, in that autism involves a general pattern of constrained overgrowth, whereas schizophrenia involves undergrowth. These disorders also exhibit diametric patterns for traits related to social brain development, including aspects of gaze, agency, social cognition, local versus global processing, language, and behavior. Social cognition is thus underdeveloped in autistic-spectrum conditions and hyper-developed on the psychotic spectrum. We propose and evaluate a novel hypothesis that may help to explain these diametric phenotypes: that the development of these two sets of conditions is mediated in part by alterations of genomic imprinting. Evidence regarding the genetic, physiological, neurological, and psychological underpinnings of psychotic-spectrum conditions supports the hypothesis that the etiologies of these conditions involve biases towards increased relative effects from imprinted genes with maternal expression, which engender a general pattern of undergrowth. By contrast, autistic-spectrum conditions appear to involve increased relative bias towards effects of paternally expressed genes, which mediate overgrowth. This hypothesis provides a simple yet comprehensive theory, grounded in evolutionary biology and genetics, for understanding the causes and phenotypes of autistic-spectrum and psychotic-spectrum conditions.

Keywords: autism, cognition, genomic conflict, genomic imprinting, hyper-mentalism, psychosis, schizophrenia

People divide roughly, it seems to me, into two kinds, or rather a continuum is stretched between two extremes. There are people people and things people. —W. D. Hamilton (2005, p. 205)

(Full Text is here, get it as long as it lasts...)

Edit:

One more: NMDA receptor dysfunction in autism spectrum disorders

Abnormalities and imbalances in neuronal excitatory and inhibitory synapses have been implicated in diverse neuropsychiatric disorders including autism spectrum disorders (ASDs). Increasing evidence indicates that dysfunction of NMDA receptors (NMDARs) at excitatory synapses is associated with ASDs. In support of this, human ASD-associated genetic variations are found in genes encoding NMDAR subunits. Pharmacological enhancement or suppression of NMDAR function ameliorates ASD symptoms in humans. Animal models of ASD display bidirectional NMDARdysfunction, and correcting this deficit rescues ASD-like behaviors. These findings suggest that deviation of NMDAR function in either direction contributes to the development of ASDs, and that correcting NMDAR dysfunction has therapeutic potential for ASDs.