death apple

CW mental health, stress, academic work, brain determinism, dysphoria.

Late last night drank again coffee so as to be able to work another two hours. It was a bad idea regardless because unlike in the past, 7dl coffee at 22 prevented me now from falling asleep at 03. In the end, slept some, possible through low-dose atarax and phenibut. Cancelled some meetings, cut others short, emotional but kept under control during day – felt disapproval of collaborator for how slowly we have delivered on one project, felt helpless from not being able (or willing) to force my postdoc to work faster.

Finally ended up on train ride. There is so much to do in regards to real work, and it frustrates me that I will have so little time for it during the next few days of my course; I will have to somehow do data crunch and coding and emails during the night, plus a planned phone conference. This causes a sense of fear because I know I have to do this, have to make it work.

To add insult to injury, I came across a new Nature article that fucks me up further ( https://www.nature.com/articles/s41398-020-0742-9 ). It is not bad science, nor is the pursuit of this knowledged bad, nor are the methods so flawed. It moves Sry genes around and includes gonadectomies to test for sex differences between animals in a way that separates genetic (double X chromosome double expression dosage for genes escaping X-inactivation, actual Y gene expression in adults (Sry apparently expresses in adult mouse brain)) from organizational (sex hormone levels during development and puberty changing reactivities for later) from each other and from either anatomy (since you have XX mice with testes, XY mice with ovaries this way) or circulating hormone levels.

Long ago I blogged about major depressive disorder, how it corresponds to very different brain activation networks in men and women. Apparently, from these results, inducing MDD-like disease in mice from chronic stress similarly causes almost entirely different gene networks and interregion patterns to activate between XY male and XX female mice, in line with this. Phenotypes may be similar, but mechanisms (which are heavily immune linked, interestingly) seem robustly very different, and these differences trace to both the genetic sex effect and to the organizational influence.

While the same authors previously showed similar things (but without the whole transcriptome level data) on genes involved in GABA and anxiety, they also showed in that earlier study that circulating testosterone impacted these behaviours independently of either gonadal (organizational and mouse cultural, such as it is) and genetic status, this leaves me still with the heavily dysphoric observation that for a dyadic trans woman (not karyotypically intersex), none of the changes we undergo with HRT reduce this vast set of gene expression/mechanism differences that separate us from cis women (some of which represent development terminal differentiation, which a CAIS XY woman would not have, some of which represent dosage effect, which a CAIS XY woman would have). While there may well be even more differences emerging between non-gonadectomied cis men and women, this is still a major difference.

I saw before this being the case for liver, that inflammation and starvation systems differ majorly between cis men and women (by extension) due to chromosome direct effects in a way which I cannot currently eliminate through transition treatment. But liver is less important. Systems like depression and anxiety are core to who we are. Fearing their mechanistic difference (even under similar observed behaviour) between me and my cisters make me feel extremely and terribly dysphoric, worried that I cannot fully understand the experience of a depressed XX person as a result, that I am shut out, able only to understand the men. It evokes, through no fault of the study authors, perceptions of essential prisons. I feel such thoughts as lead-heavy, death-urgent dysphoria.

Probably it is not quite so terrible as it seems, because more systems may be more subtly involved. These groups of many correlated genes imply this is the effect of a few top regulator factors cascading, and the immune involvement implies a system at least in part separable from the pure mood phenotype (and does not reveal, in this manner, causality). But linked to the functional network views this still is very dire (though perhaps those network changes also reflect more a consequence than cause of the experiential phenotype).

But the way I respond is terribly dark. I feel again like I learned I died, like my loved ones died, disappeared. I sense waves of hate and disgust over my body – not just the deformed parts which makes people see and hear me as male, but right now I feel no pride or happiness over my brain or personality either. What if through my garbage Sry and lack of a second X, and the times of my life from conception spent misassembling my chromatin under testosterone poisoning, what if from that I am doomed to function (under stress, anxiety, depression but also their resilience and counterparts) in some manner which is unavoidably like male persons, leaving me unable to fully understand on an emotional level my sisters? It makes me feel fully and wholly dissociated from this rotting corpse body and from my thoughts and emotions, too, leaving me like a skull or shard inside something which holds neither thought or emotion. Dead. Never alive.

I had more coffee and two emergency phenibut, and I am glad I brought more on this journey in case I will risk being sleepless in next nights (fun fact: systems studied here ALSO are involved in phenibut action). I wanted to not use it so much, and hope to cease to need it, but this places me in such sad darkness. Of course it is not so bad as it seems. A Turner X0 woman or CAIS XY woman has many of these effects in place, yet is no less a woman for that. A CAH XX woman might have some of the other effects, and is also no less a woman (unless, like some elevated fraction of CAH people, he is a trans man).

Sanity requires I accept somehow that there are even important aspects of my neurobiology where my current husk of a body functions like men function, but that this does not diminish my womanhood. I am an atypical woman, like a combination of multiple intersex conditions as well as some unique ones. I am still female in all ways I am, for all that. I just feel dysphoric over my chemistry or transcription profile or epigenome in the exact same way as I do over my awful voice or big head or hands, or damnable genitals. Disgusting, but I change all I can.

Not for the first time I find myself wondering, can we build on this? Can we somehow activate these programs differently? Can we treat this in transition care? For liver I was hoping to rebuild the organ with the right karyotype and epigenetics, but of course eventually that might lead to immune incompatibility (or not? Perhaps cell differentiation cannot break the own/vs foreign influence?). But could we mimic the effect of an XX karyotype by somehow elevating expression of the genes in question? It would be hard, not least because this all might be tissue specific. If nothing else, then the fact these are interlinked gene networks would make it easier than it could be. But still risky, might lead to uncontrolled growth.

And of course there will also be direct hormone effects, relevant ones, and those I do fix. And some terrible cases where early exposure may mean I cannot benefit from my new estrogen balance the way I could have without early testosterone exposure. It is all terrible, and I see as yet no way to fix myself the way I would want. (And it seems XY genotype increases anxiety risks where circulating T reduces it, implying XX compensates a little through dosage compensation for lower T, and placing me as an XY woman in even higher risk of anxiety since I definitely want no more T. Be that as it may.)

Though I suppose as a mad science witch I should have goals. Defeating death is not enough, becoming biologically exactly the same as a cis girl is the other thing I need. But while the rest can be replaced, the brain is harder. Can’t clone a new XX brain and replace my present one with it, my individuality would not come along. Now even the thought of my mind and personality disgusts me, how much of it is dependent on these awful male-like system differences?

(Spirit. You should read this paper, it is good and will interest you. Understanding networks underlying major depressive disorder, which you almost certainly have, with anhedonic subtype, that is one application of network work and epigenomics that might address this major disease. It lies very well within your research interest and can be a further direction you go in, even. I suggest it because perhaps you can succeed within decades even if I don’t, in working out some way of medicating these networks to mitigate such effects on a clinically relevant scale. Then I could build on that research in turn to make something that lets me and other trans sisters function more like XX people. I envy you your body, for so many reasons, but I love you deeply and I am glad that you have it, even those parts which matter much less to you than to me. If I was AFAB XX, I would probably be even more like you.)

Never mind. I am myself. I am the woman that I am, and I will change everything about me that I can. Even if my resilience and perseverence might be affected by certain types of immune activation in my brain under stress that are characteristic of the male brain, that does not deny or make unimportant all the rest of me. And I will do studies that are the opposite of this, see what factors clearly do change under transition, and take some solace in them.

I feel such sorrow and pain and envy. For all those who don’t have to do this, defend this, seek this, just to be that which I need to be.

The medication is working, at least. I am more calmly coldly focusing. I will share this with my loved ones so you know how I feel. Then I will do some work on my own science instead. Make a small dent in the mountain, working towards safety. I will never give up my willpower or resilience. I will always strive towards my goals. I just wish the world did not make it so hard. I wish I had emerged in a different genotype and phenotype.

through-a-scanner-glitteringly

So on Gliske again, came across reviewer comments. Two named, not sure which. I believe first must be Ivanka Savic, she was mostly critical – though not for the eugenics or misgendering – but for not claiming credit of ideas she considers hers. From what I can see she has published a lot of interesting things, including re: how HRT improves sense of body ownership and changes sexed perception of scent. I sort of want to work with her, though I heard from people nearer she is somewhat of a nasty person to collaborate with. These comments if hers would paint a similar picture, less a bigot, more an uncaring asshole. Her papers have not been as bad terminology-wise.

One reviewer, apparently anonymous, is a sexologist, not neuro. They (I suspect he) explicitly asked for the Blanchardianism, claims young transitioners have no body issues (then again, not as sexed bodies then), and that aversion therapy hasn’t been properly tried yet, implying they would like for it to. Claiming it has not because Zucker disputes he has done so. Reviewers overall more accepting than I would like. Then again, this is what happens when we get to suggest reviewers. This is why we do so.

I no longer think this is a side project for Gliske, he spent grant funds to have the time to do it. In initial version there was apparently a lot of reference – removed by reviewer request – to sleep disturbances, which he has worked more on. He claimed based on too little data for reviewers to like it that this would be part of trans pathology. Parents, don’t let your children stay up all night, they might be transed!

But what mostly have me commenting, to get it out of my head, is in reviewer response he gets again onto the concept of gender being encoded as “same” or “different”. I agree on the level that the core gender-constructing brain response is a universal capacity to classify perceived bodies as same or other in sense of sex, which wired one way or the other leads to decisions on desire and competition and model learning. But the way he seems to imply a model for it, he perceives trans modality as wanting to be the bodies one classifies as “other” whereas cis modality is wanting to be the bodies one classifies as “same”. This model evokes body dysmorphia, plastic surgery addiction, continually searching for something new to transform into. It would predict that transition can never be enough, that full body medical and full life social transition would just give a new intolerable state one must escape into something else. This toxic idea, of course, was one of those I worried over, that kept me questioning myself.

Can it hold? It would predict that transition cannot enduringly reduce dysphoria, unless it indirectly leads to a change in the brain so that it comes to 1) wants now to instead embody sameness, not otherness, and 2) self-perception is that one has the gender one transitioned as, or rather, reacts with “same” to oneself. Alternately, one still sees ones self as “opposite”, and continues to crave “opposite”. End result same, only in the latter such idea, our genders would somehow be something qualitatively different than cis people’s genders. It is convoluted that one would continue to regard one’s own body as “opposite” once it has stabilized, and assuming then some virtual AGAB identification one happily feels one’s body is opposite to, also feels convoluted. And dysphoria-inducing, as any other scenario that implies there is some essential true identity as my gender that I could never attain.

Transition is complex though. I keep talking of the synergy between medical, social and internal transition. By internal, I mean the alterations in how one perceives oneself and others, how one reacts, how one feels. Some such are spontaneous, some require effort; transition involves making that effort. Moreover, there are mixtures of worries and memories and insecurities, euphoria and dysphoria and problematic validation, doubt, fears of illegitimacy, and the eventual rise of a new, more relaxed normality. In the end it is important I think for me to recognize I am legitimate by virtue of my subjectivity and agency alone, even had I had not been able to reference anything external.

My simpler same-different model echoes how we classify others as same-sex or different-sex. Additionally, I postulate, we do so to ourselves. Cis people inhabit bodies and lives which they classify spontaneously as same-sex as themselves. Trans people the opposite. Transitioning changes that, but beyond ourselves, does not alter who feels “same” or “opposite” with regards to sex, nor (mostly) how we feel about that. By changing what sex we can see ourselves as, we can go from seeing ourselves as paradoxes, mismatches, to simply normal. This reduces distress, reduces sense of lack of body ownership, and makes us eventually less preoccupied with gender. There probably are direct dysphoria reactions from various aspects of HRT itself acting on the brain, but the changes to our bodies are crucial also, something Gliske appears not to realize. Knowing others can see me as a woman makes me comfortable being seen. This is also why some dysphoria reduction can be achieved already by presentation and social transition alone, which again is not fully recognized by this “model”.

I followed up references made to a 2019 Savic paper where her team put 15 cishetero men and 15 cishetero women in a brain scanner and systematically showed them their own body, that of same and opposite sex others, and morphs between them, assing perception of “me/not-me” by self-declaration and imaging data. This is in principle highly relevant. They show own-body perception to involve mostly same brain regions in these men and women; Gliske references this in support for his same-other brain classifier dichotomy but of course it fits equally well with mine. There are other parts of the paper (Burke et al., 2019: Sex differences in own and other body perception [ https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24388 ] ) that are interesting; seeming congruent with somewhat (N = 15+15, brain imaging statistics caveats, presumably overlapping distributions) greater salience of own body for women, others’ bodies for men, more possible inspect-for-partner vs inspect-for-rivalry in men, etc. The descriptions the paper makes of women sounds like trans girls honestly – own body critical and focused, identifying other women also as self, etc. But tiny, who knows what can be reproduced and then hardly absolute.

It would be a literature of interest to look into but it also severely scare me, because what if brain imaging gets better and more robust so that it would become emergent that trans women (or just me, the awful impostor…) did not react the way I think we do in terms of perception and response, but like twisted versions of our AGABs. Important to remember then – the subjectivity is what matters in this case, brains are plastic and might not locate functions uniformly, HRT has already been shown to change brain functional connectivity. The latter also supported indirectly by another paper I randomly came across – placing CAIS XY women in brain scanners yield the same responses as for cis XX women when shown nudes, compared to cis XY men. So whatever is there in such activation at least is not chromosomal. It may reflect some organizational effects, not just activational, but over time, who knows what we can become?

And as noted, the real crucial insight is – my agency and my feelings, however they arose, however they are implemented, are what matters for me. I believe strongly my brain has differences from that of a cis man, but whether it does or not, I am changing over time into someone I am much happier being, and my life as a result is better. I will that life into reality, no matter what stands against me.

tiphareth IV

These are days of force going up and down. All in all I am so blessed. There is so much to challenge, but I feel the world unfold. Life is adventure.

I must learn the saran wrap technique, must try it. My estradiol levels were not tested after I started gel, so I worry perhaps I misapply and my levels may be too low? Next check is scheduled for March. But there is no fear – I no longer masculinize, so even delays in my change are only temporary setbacks.

With too many crucial and important things at once I must learn to force relaxation. It is so hard. I must set evenings when I do nothing, not even emotional labor, not even quick email answers. Certainly not late chatting. I must set days when I do nothing productive, only go see new parts of Babylon, or try to write more intense words than these. I must set days when I work on forgotten projects only, or long-term projects only, despite any urgency, days when I just read. I must start placing these into my calendar, schedule nothing conflicting then, and adhere to them.

I know this is truth and that I can do it. Nothing stops me. It is still difficult. But nothing stops me. I am alive now. I know it is what I need, so I must do it.

Similarly, I must do what is needed for health. It seems documents will not be an issue, so after the consultation in April I can decide on surgery – if, and when, and where. And if as I now am leaning to, and I will go to Chettawut in Bangkok, and if I have the funding ready, then perhaps I have no reason to delay. I’m trying to get used to the really scary thought of doing it in December. Maybe one of my partners can join. I can’t assume they will, so will keep that open, for whomever can. And thereafter, after the first month, will I spend one in my country of origin? Or will I stay in Babylon, receving guests?

It scares immensely. It must and I must process it even more before April, so I will be ready to decide then.

I fear somehow having a heart condition. I don’t think I do, but I must minimize the risk so I am not denied. So this year is the strict deadline for perfection, isn’t it? What should I do?

I should attempt to make real – again, I can, I just have to dare schedule it – so that I sleep closer to eight than six hours each night.

I should attempt to reach fully where I want to be with the fasting, and keep diligent with probiotics and vitamins. I need to minimize risk for blood clotting, optimize blood circulation. So I should also begin cardio exercise. This is even harder in terms of finding time. I cannot become sick. So I must dress warmly, from now on.

That effort with voice, that must continue.

I relax into these preparations. Certainly there is also here a factor of having a complex goal and vast ordeal being something which empowers me. After surgery, which will mine be correspondoingly? Asides from all my other goals? I will find one, certainly.

Emotionally, I learn to be ebb and flow. I write heart-baring words and then brood over whether to send them.

The sun is shining today in terrible glory.