Etiological Conjectures, Part 2
As I alluded in my previous post, scientists also like to speculate and generate conjectures regarding the etiology of transsexuals. In this post, I will explore and comment on some of them.
Many of the earlier conjectures were highly influenced by psychoanalysis, shoehorning observations into existing, yet completely untested, models of psycho-sexual development. These were largely psychogenic theories, that is to say, that mental process create the condition, either transsexuality or homosexuality. More specifically, they theorized that family constellations, usually an overly involved mother and a distant father create the conditions whereby a male child gets the erroneous idea that they must be female, as they can’t separate themselves as individuals from their mothers. Or, the theory might be that fear of losing their precious penis causes them to overly-identify with their mother so that losing it doesn’t seem such a bad alternative. (Yes, I’m over simplifying, deliberately, sarcastically.)
Before we completely laugh at the idea of psychogenic illness, we should remember that there are several very real psychiatric illnesses which have been identified and shown, using modern science, to be of such psychogenic origin. The most heart breaking is Reactive Attachment Disorder, which is common among institutionalized children who as babies and toddlers were literally not cuddled. The lack of physical / emotional contact with caregivers literally creates a condition whereby these children have severe emotional and behavioral problems as they grow up (but not autism). Another illness that has a psychogenic origin is post-traumatic stress disorder. Although traumatic events as adults act as the proximate trigger, horrific events in childhood have been identified as leaving these individuals without the emotional resilience to weather such events. A history of physical abuse as a child is one of the more commonly identified preconditions for later post-traumatic stress syndrome, likely due to down-regulation of cortisol production.
But, during the early to mid-twentieth century, psychoanalysis claimed illnesses were psychogenic that we now have clearly established as neurological defects including schizophrenia and autism spectrum disorders. Typically, the quality of mothering was blamed. (Sound familiar?) Mothers were blamed for nearly every sort of bad outcome in their children, without ANY corroborating statistics or evidence. The ugliest of these was calling the mothers of autistic children, “refrigerator mothers” and the mothers of schizophrenic young adults, “schizogenic mothers”.
So, in a similar vein, I call the theories that invoke parenting styles, especially those that blame mothers, for MTF transkids, the “smother mother” hypothesis. Without ANY corroborating statistics or evidence, many psychoanalysts and their medical colleagues, accepted many of these theories as “true”. Although it is true that many parents become emotionally distant from a transkid, this is far more likely a result, not a cause, of the child’s gender atypical behavior. These theories, although largely abandoned by scientists, still seem to have currency with a number of therapists that I’ve talked to. In one odd conversation I had about two decades ago, an elderly therapist acknowledged that it didn’t seem to be true of her “early transitioners”, but she was convinced that her “late transitioners and transvestites” had come from such families with smothering mothers and distant fathers. During the conversation, I began to suspect that she was guilty of confirmation bias and of subtly “coaching” her clients in what she expected them to say, so that they could obtain their “letters”.
To a modern scientifically based intellect, the creation and wide scale acceptance of psychodynamic theories about the origins of both typical and atypical gender and sexual behavior seems incomprehensible. How could they ever even entertain such odd notions? But, if we understand that the ideas have at their core, the pre-Darwinian notion that humans are a special creation, unlike any other species on the planet, it starts to make some sense. While to us, the thought that gendered and sexual behavior comes from a mental process that, if we translated to our rodent cousins, would make it sound, and be, ludicrous: Baby rat sees Daddy rat’s penis and notices she doesn’t have one… and envies Daddy rat’s penis… so she starts acting like Mommy rat to get Daddy rat’s affectional attention, etc. But, if humans are special creation, the theory doesn’t have to work for our rodent, or even, or maybe especially (?) our primate cousins. These notions had their genesis in Late-Victorian Europe, which was then struggling with the implications of Darwin’s theory of natural selection and evolution and spread to North America which is still struggling (!) .
Another hypothesis is that an anomalous hormonal environment causes cross-sex neurological development. This is bolstered by experimental research in various animal models, usually rodents, in which exogenous hormonal intervention at certain critical times in neurological development induces cross-sex behaviors. When coupled with the discovery of cross-sex neurological features in the brain, this would seem to clinch the matter. Yet… and yet… it doesn’t explain how or why these events occur in otherwise phenotypically normal individuals. Further, phenotypical markers of prenatal hormone exposure, such as the 2D:4D finger ratio have failed to provide consistent, reproducible, results.
Thus was born the “gay gene” hypothesis. Studies of gay men and MTF transkids consistently show evidence of consanguinity, that male homosexuality and exclusive androphilic MTF transsexuality both run in families. However, the idea of a “gay gene” caused problems with evolutionary theory, since how could such a genetic allele continue to exist against the obvious reproductive disadvantage that being gay (or transkid) naturally presented. Researchers have spent the past two decades searching for an evolutionary advantage that the relatives of gay men and transkids might enjoy as a “carrier” of the putative “gay gene”. But years of searching have failed to find such a gene(s). Perhaps that’s because, there isn’t one?
Finally, we have our new variant on the “gay gene”, the “gay epigene”. An epigenetic model is based on the recognition that genes are controlled and regulated by other genes using chemical tags, dangling links, attached to the DNA in each and every cell in the body. These marks are like the conditional branch points, the “flags” or variables, of a computer program. The interesting thing about such epi-marks is that though it is believed that they should all be erased between generations, many of them are not always fully erased. This might be a mistake… or it might even be an evolved ability for a crude form of transgenerational gene regulation “memory”. For example, if an organism needs to adjust it’s metabolism to lean times, like not enough food, by becoming careful about not burning off fat too quickly, it might be advantageous to their progeny to have that adjustment already turned on. Just such a behavior has been seen in humans, where grandchildren of individuals who knew starvation have slower metabolisms than individuals whose grandparents and parents never knew such lean times.
One of the earliest models to include an epigenetic explanation was from Richard Green M.D., ( a stalwart friend of the transsexual community) and E.B. Keverne, a noted geneticist. This model suggests that the failure to erase/modify epigenetic markers on the X chromosome that are supposed to be passed down to only one generation, but when passed down past that generation, are theorized to cause severe harm:
A significant skewing in the sex ratio in favour of females has been reported for the families of homosexual men such that there are fewer maternal uncles than aunts. This finding is repeated for a large series of transsexual families in this study. Four hundred and seventeen male-to-female transsexuals and 96 female-to-male transsexuals were assessed. Male-to-female transsexuals have a significant excess of maternal aunts vs. uncles. No differences from the expected parity were found for female-to-male transsexuals or on the paternal side. A posited explanation for these findings invokes X inactivation and genes on the X chromosome that escape inactivation but may be imprinted. Our hypothesis incorporates the known familial traits in the families of homosexuals and transsexuals by way of retention of the grand parental epigenotype on the X chromosome. Generation one would be characterized by a failure to erase the paternal imprints on the paternal X chromosome. Daughters of this second generation would produce sons that are XpY and XmY. Since XpY expresses Xist, the X chromosome is silenced and half of the sons are lost at the earliest stages of pregnancy because of the normal requirement for paternal X expression in extra-embryonic tissues. Females survive by virtue of inheriting two X chromosomes, and therefore the possibility of X chromosome counting and choice during embryonic development. In generation three, sons inheriting the paternal X after its second passage through the female germline survive, but half would inherit the feminizing Xp imprinted genes. These genes could pre-dispose the sons to feminization and subsequent development of either homosexuality or transsexualism.
The latest attempt to explain the presence of homosexuality goes into greater detail of how epigenetic markers canalize (channel) the sex hormone influenced masculinization in males or protect against such masculization in females. This model assumes that all of the epimarkers should have been erased between generations, but the ones from the cross-sex parent were not fully erased:
It is well established that fetal androgen signaling strongly influences sexual development. We show that an unappreciated feature of this process is reduced androgen sensitivity in XX fetuses and enhanced sensitivity in XY fetuses, and that this difference is most feasibly caused by numerous sex-specific epigenetic modifications (“epi-marks”) originating in embryonic stem cells. These epi-marks buffer XX fetuses from masculinization due to excess fetal androgen exposure and similarly buffer XY fetuses from androgen underexposure. Extant data indicates that individual epi-marks influence some but not other sexually dimorphic traits, vary in strength across individuals, and are produced during ontogeny and erased between generations. Those that escape erasure will steer development of the sexual phenotypes they influence in a gonad-discordant direction in opposite sex offspring, mosaically feminizing XY offspring and masculinizing XX offspring. Such sex-specific epi-marks are sexually antagonistic (SA-epi-marks) because they canalize sexual development in the parent that produced them, but contribute to gonad-trait discordances in opposite-sex offspring when unerased. In this model, homosexuality occurs when stronger-than-average SA-epi-marks (influencing sexual preference) from an opposite-sex parent escape erasure and are then paired with a weaker-than-average de novo sex-specific epi-marks produced in opposite-sex offspring. Our model predicts that homosexuality is part of a wider phenomenon in which recently evolved androgen-influenced traits commonly display gonad-trait discordances at substantial frequency, and that the molecular feature underlying most homosexuality is not DNA polymorphism(s), but epi-marks that evolved to canalize sexual dimorphic development that sometimes carryover across generations and contribute to gonad-trait discordances in opposite-sex descendants.
This model has much to recommend it. For instance, it would fit with the conjecture I made in my last post regarding the possibility of multiple semi-independent genes controlling sexually dimorphic behavior being involved. Yet,the odd thing about this recently published paper is that the authors seem to have no understanding of the nature of homosexuality and the close relationship it has with transkids, childhood gender atypicality, childhood gender dysphoria in desisting pre-homosexuals, and persisting transkids. Incredibly, they actually predict that such epigenetic marking will have no correspondence with “gender identity”:
We describe our hypothesis for an epigenetic cause of homosexuality as a series of statements (see Figure 3 for a graphical summary):
a) Empirical studies demonstrate that XX fetuses are canalized to blunt androgen signaling (lower sensitivity to T) and XY fetuses are canalized to boost androgen signaling (higher sensitivity to T).
b) Empirical studies demonstrate the production of XX- and XY-induced epi-marks in embryonic stem cells and extensive sex-specific differences in gene expression at this time. Epi-marks laid down during the embryonic stem cell stage are also established to influence gene expression later in development. This stem cell period is the most plausible candidate time point for the production of epi-marks influencing sensitivity to androgens later in development (canalization of fetal androgen signaling).
c) Epi-marks produced in embryonic stem cells are mitotically transmitted to cell lineages leading to both the soma and the germline, and hence can contribute to pseudo-heritability when they escape erasure across generations (nonerasure in the primordial germ cells and in the zygote and first few cell divisions of the next generation). Animal models as well as human data unambiguously demonstrate that such a multistep escape from erasure does occur at nontrivial frequency.
d) Epi-marks blunting (in XX fetuses) or boosting (in XY fetuses) androgen signaling will be sexually antagonistic (SA-epi-marks) when they have a nonzero probability of carryover across generations and are expressed in oppose sex descendants. Such carryover will contribute to discordance between the gonad and one or more sexually dimorphic traits.
e) Our modeling work shows that SA-epi-marks are favored by natural selection over a broad span of parameter space because there is a net benefit to the carrier (due to canalization of sexually dimorphic development) that is not offset sufficiently by transmission (and fitness reduction) to opposite sex descendants.
f) Genetic mutations causing SA-epi-marks are expected to fix in populations and are therefore not expected to be polymorphic except transiently during their initial spread within a population. Therefore, no association between genotype and homosexuality is predicted.
g) Because the androgen signaling pathways differ among organs and tissues (e.g., use of different AR cofactors), the same inherited SA-epi-mark can affect only a subset of sexually dimorphic traits, e.g., no effect on the genitalia, but a large effect on a sexually dimorphic region of the brain.
h) Shared, gonad-discordant SA-epi-marks that carryover across generations would contribute to the observed realized heritability of homosexuality, e.g., monozygotic twins share the same SA-epi-marks coinherited from a parent.
i) Unshared, gonad-concordant SA-epi-marks, produced during fetal development, would contribute to the low proband concordance of homosexuality observed between monozygotic twins, i.e., they need not share SA-epi-marks generated during development that occurs after the twins have separated.
j) Homosexuality occurs when an individual inherits one or more gonad-discordant SA-epi-marks that are not masked nor erased by the production of de novo gonad-concordant SA-epi-marks that accrue during ontogeny. The SA-epi-mark(s) influence androgen signaling in the part of the brain controlling sexual orientation, but not the genitalia nor the brain region(s) controlling gender identity.
Perhaps they are referring not to the existence of transkids “gender identity” but of the “gender identity” of autogynephilic transsexuals? If so, I would TOTALLY agree with them. But, somehow, I believe that they are simply basing this odd assertion on the mistaken acceptance of our late 20th Century adoption of the separation of sexual orientation and gender identity as being unrelated phenomena, without having read the scientific literature dispelling it.
Thus, we see that cultural biases have and continue to distort scientific discourse into the etiology of homosexual transsexuality.
David E. Simpson, J.J. Hanley, Gordon Quinn, Documentary film: “Refrigerator Mothers”
Green, R., Keverne, EB., The disparate maternal aunt-uncle ratio in male transsexuals: an explanation invoking genomic imprinting.
Rice, et al. “Homosexuality as a Consequence of Epigenetically Canalized Sexual Development”