Tuesday, 22 July 2008

More Parts of the Puzzle

CNN is now reporting on the same kind of research on opposite-sex twins that I mentioned in BiGender and the Brain.

And the latest issue of Cerebral Cortex has an article, Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. by Berglund H, Lindström P, Dhejne-Helmy C, and Savic I.

As per usual, lesbian MtoF women are described as "nonhomosexual". One day, the penny will drop.

From the article itself (rather than the online abstract) :
Transsexuals have the strong feeling, often from childhood onward, of having been born the wrong sex. The possible etiology of transsexualism has been the subject of debate for many years (Benjamin 1967; van Goozen et al. 2002; Swaab 2004; Gooren 2006). Investigation of the genetics, hormone levels, gonads, and genitalia of transsexuals has not produced results that explain their status (van Goozen et al. 2002; Swaab 2004; Gooren 2006). In experimental animals, the gonadal hormones that prenatally determine the morphology of the genitalia are shown to also influence the morphology and function of the brain in a sexually dimorphic manner (Fels and Bosch 1971; Yalom et al. 1973; Baum 2003 2006). This led to the hypothesis that sexual differentiation of the brain in transsexuals might not have followed the line of sexual differentiation of the body as a whole and that transsexual persons may have sex-atypical cerebral programing (van Goozen et al. 2002). Such a scenario can be evaluated in humans by comparing transsexual and control subjects with respect to sexually differentiated cerebral functions.
In the quest for reliable in vivo methods to study sex differences in the neurobiology of the hypothalamus, we designed positron emission tomography (PET) activation experiments measuring changes in regional cerebral blood flow (rCBF) during smelling of 2 steroidal compounds: the progesterone derivative 4,16-androstadien-3-one (AND) and the estrogen-like compound estra-1,3,5(10),16-tetraen-3-ol (EST) (Savic et al. 2001, 2005; Berglund et al. 2006). AND is present in human male secretions such as sweat, saliva, and semen (Grosser et al. 2000), whereas EST has been detected in the urine of pregnant women (Thysen et al. 1968).
Several centers currently recognize essentially 2 types of MFTRs who can be distinguished on the basis of their sexual orientation (Chivers and Bailey 2000; Smith et al. 2005). The first type is homosexual transsexuals, extremely gender-transposed (feminine) men, whose sexual object choice is toward men instead of women. The second type is men, whose sexual object choice is interpreted to be toward the image of themselves as women. For this group, the primary motivation for changing sex is to become the object of their own desire (Chivers and Bailey 2000; Smith et al. 2005). In this respect, all our patients can be regarded as nonhomosexual (gynaecophyl) transsexuals (Chivers and Bailey 2000), although we used a more operative approach in our classification, taking into consideration also the sexual partners, sexual fantasies, and expressed attractions (Kinsey 1953Go).
They have a very diplomatic way of saying that Civers and Bailey are full of it. Because "men, whose sexual object choice is interpreted to be toward the image of themselves as women" would hardly have female anatomy, would they? If they did, then how could we classify them as "men", except arbitrarily? And the studies show pretty conclusively that they do have at least feminised anatomy, when it comes to parts of the brain.
The generated data relate to reports by Swaab's group of a female size of BNSTc in MFTRs (Zhou et al. 1995Go; Kruijver et al. 2000Go). Although structural and functional dimorphism are not directly translatable and the BNST is too small to be detected with the imaging methods applied, it is of note that this nucleus in animals mediates pheromone signaling and that it in humans has reciprocal connections with the anterior hypothalamus (Eiden et al. 1985Go). Both Swaab's and our findings may, therefore, reflect a common organizational deviation of certain sexually dimorphic circuits involved in human reproduction. Whether and how this links to the perception of sexual identity remains unclear and awaits further investigations.
I would have said "gender identity and sexual orientation", two separate concepts, but no matter.
In summary, albeit the present study does not provide conclusions concerning the possible etiology, it suggests that in transsexuals the organization of certain sexually dimorphic circuits of the anterior hypothalamus could be sex atypical. It adds a new dimension to our previous reports by showing that the observed effects are not necessarily learned and that a sex-atypical activation by the 2 putative pheromones may reflect neuronal reorganization.
Having had a look at the study, they went to extraordinary lengths to shackle all the variables. They even insisted on only right-handed subjects being included. All in all, extremely good Science.

At some stage... eventually... the American Psychiatric Association and others are going to realise that they can't continue to ignore the neurological data in favour of psychiatric conjectures.

And finally, for my own reference as much as anything else, their list of articles:

Allen LS, Hines M, Shryne JE, Gorski RA. Two sexually dimorphic cell groups in the human brain. J Neurosci (1989) 9:497–506.[Abstract]

American Psychiatric Association Task Force on DSM–IV. Diagnostic and statistical manual of mental disorders: DSM–IV (1994) Washington, DC: American Psychiatric Association.

Baum MJ. Activational and organizational effects of estradiol on male behavioral neuroendocrine function. Scand J Psychol (2003) 44:213–220.

Baum MJ. Mammalian animal models of psychosexual differentiation: when is ‘translation’ to the human situation possible? Horm Behav (2006) 50:579–588.

Benjamin H. The transsexual phenomenon. Trans N Y Acad Sci (1967) 29:428–430.

Bensafi M, Brown WM, Khan R, Levenson B, Sobel N. Sniffing human sex–steroid derived compounds modulates mood, memory and autonomic nervous system function in specific behavioral contexts. Behav Brain Res (2004) 152:11–22.

Bensafi M, Tsutsui T, Khan R, Levenson RW, Sobel N. Sniffing a human sex–steroid derived compound affects mood and autonomic arousal in a dose–dependent manner. Psychoneuroendocrinology (2004) 29:1290–1299.

Berglund H, Lindstrom P, Savic I. Brain response to putative pheromones in lesbian women. Proc Natl Acad Sci U S A (2006) 103:8269–8274.[Abstract/Free Full Text]

Blanchard R. The classification and labeling of nonhomosexual gender dysphorias. Arch Sex Behav (1989) 18:315–334.

Canli T, Gabrieli JD. Imaging gender differences in sexual arousal. Nat Neurosci (2004) 7:325–326.

Chivers ML, Bailey JM. Sexual orientation of female–to–male transsexuals: a comparison of homosexual and nonhomosexual types. Arch Sex Behav (2000) 29:259–278.

Cohen H, Forget H. Auditory cerebral lateralization following cross–gender hormone therapy. Cortex (1995) 31:565–573.

Cohen–Kettenis PT, van Goozen SH, Doorn CD, Gooren LJ. Cognitive ability and cerebral lateralisation in transsexuals. Psychoneuroendocrinology (1998) 23:631–641.

Eiden LE, Hokfelt T, Brownstein MJ, Palkovits M. Vasoactive intestinal polypeptide afferents to the bed nucleus of the stria terminalis in the rat: an immunohistochemical and biochemical study. Neuroscience (1985) 15:999–1013.

Fels E, Bosch LR. Effect of prenatal administration of testosterone on ovarian function in rats. Am J Obstet Gynecol (1971) 111:964–969.

Frackowiak RSJ. Human brain function (2004) Amsterdam (London): Elsevier Academic.

Friston KJ, Holmes A, Poline JB, Price CJ, Frith CD. Detecting activations in PET and fMRI: levels of inference and power. Neuroimage (1996) 4:223–235.

Friston KJ, Holmes AP, Worsley KJ. How many subjects constitute a study? Neuroimage (1999) 10:1–5.

Gooren L. The biology of human psychosexual differentiation. Horm Behav (2006) 50:589–601.

Gottfried JA, Deichmann R, Winston JS, Dolan RJ. Functional heterogeneity in human olfactory cortex: an event–related functional magnetic resonance imaging study. J Neurosci (2002) 22:10819–10828.[Abstract/Free Full Text]

Grosser BI, Monti–Bloch L, Jennings–White C, Berliner DL. Behavioral and electrophysiological effects of androstadienone, a human pheromone. Psychoneuroendocrinology (2000) 25:289–299.

Haraldsen IR, Egeland T, Haug E, Finset A, Opjordsmoen S. Cross–sex hormone treatment does not change sex–sensitive cognitive performance in gender identity disorder patients. Psychiatry Res (2005) 137:161–174.

Hillert L, Musabasic V, Berglund H, Ciumas C, Savic I. Odor processing in multiple chemical sensitivity. Hum Brain Mapp (2007) 28:172–182.

Jacob S, Garcia S, Hayreh D, McClintock MK. Psychological effects of musky compounds: comparison of androstadienone with androstenol and muscone. Horm Behav (2002) 42:274–283.

Jacob S, Hayreh DJ, McClintock MK. Context–dependent effects of steroid chemosignals on human physiology and mood. Physiol Behav (2001) 74:15–27.
Jones–Gotman M, Zatorre RJ. Olfactory identification deficits in patients with focal cerebral excision. Neuropsychologia (1988) 26:387–400.

Karama S, Lecours AR, Leroux JM, Bourgouin P, Beaudoin G, Joubert S, Beauregard M. Areas of brain activation in males and females during viewing of erotic film excerpts. Hum Brain Mapp (2002) 16:1–13.

Kimura D. Sex, sexual orientation and sex hormones influence human cognitive function. Curr Opin Neurobiol (1996) 6:259–263.

Kinsey AC. Sexual behavior in the human female (1953) Philadelphia (PA): Saunders.

Kruijver FP, Zhou JN, Pool CW, Hofman MA, Gooren LJ, Swaab DF. Male–to–female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab (2000) 85:2034–2041.[Abstract/Free Full Text]

La Torre RA, Gossmann I, Piper WE. Cognitive style, hemispheric specialization, and tested abilities of transsexuals and nontranssexuals. Percept Mot Skills (1976) 43:719–722.

LeVay S. A difference in hypothalamic structure between heterosexual and homosexual men. Science (1991) 253:1034–1037.[Abstract/Free Full Text]

Lundstrom JN, Goncalves M, Esteves F, Olsson MJ. Psychological effects of subthreshold exposure to the putative human pheromone 4,16–androstadien–3–one. Horm Behav (2003) 44:395–401.

Lundstrom JN, Olsson MJ. Subthreshold amounts of social odorant affect mood, but not behavior, in heterosexual women when tested by a male, but not a female, experimenter. Biol Psychol (2005) 70:197–204.

Lundstrom JN, Olsson MJ, Schaal B, Hummel T. A putative social chemosignal elicits faster cortical responses than perceptually similar odorants. Neuroimage (2006) 30:1340–1346.

McGlone J. Sex differences in functional brain asymmetry. Cortex (1978) 14:122–128.

Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia (1971) 9:97–113.

Royet JP, Koenig O, Gregoire MC, Cinotti L, Lavenne F, Le Bars D, Costes N, Vigouroux M, Farget V, Sicard G, et al. Functional anatomy of perceptual and semantic processing for odors. J Cogn Neurosci (1999) 11:94–109.[Abstract/Free Full Text]

Savic I, Berglund H, Gulyas B, Roland P. Smelling of odorous sex hormone–like compounds causes sex–differentiated hypothalamic activations in humans. Neuron (2001) 31:661–668.

Savic I, Berglund H, Lindstrom P. Brain response to putative pheromones in homosexual men. Proc Natl Acad Sci U S A (2005) 102:7356–7361.[Abstract/Free Full Text]

Savic I, Gulyas B, Larsson M, Roland P. Olfactory functions are mediated by parallel and hierarchical processing. Neuron (2000) 26:735–745.

Schaltenbrand G, Bailey P. Einfèuhrung in die stereotaktischen Operationen: mit einem Atlas des menschlichen Gehirns. [Introduction to stereotaxis, with an atlas of the human brain] (1959) Stuttgart (Germany): G. Thieme.

Slijper FM, Drop SL, Molenaar JC, de Muinck Keizer–Schrama SM. Long–term psychological evaluation of intersex children. Arch Sex Behav (1998) 27:125–144.

Smith YL, van Goozen SH, Kuiper AJ, Cohen–Kettenis PT. Transsexual subtypes: clinical and theoretical significance. Psychiatry Res (2005) 137:151–160.

Sobel N, Prabhakaran V, Desmond JE, Glover GH, Goode RL, Sullivan EV, Gabrieli JD. Sniffing and smelling: separate subsystems in the human olfactory cortex. Nature (1998) 392:282–286.

Swaab DF. Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation. Gynecol Endocrinol (2004) 19:301–312.

Swaab DF, Fliers E. A sexually dimorphic nucleus in the human brain. Science (1985) 228:1112–1115.[Abstract/Free Full Text]

Talairach J, Tournoux P. Co–planar stereotaxic atlas of the human brain: 3–dimensional proportional system: an approach to medical cerebral imaging (1988) New York: Thieme.

Thysen B, Elliott WH, Katzman PA. Identification of estra–1,3,5(10),16–tetraen–3–ol (estratetraenol) from the urine of pregnant women (1). Steroids (1968) 11:73–87.

van Goozen SH, Slabbekoorn D, Gooren LJ, Sanders G, Cohen–Kettenis PT. Organizing and activating effects of sex hormones in homosexual transsexuals. Behav Neurosci (2002) 116:982–988.

Wyart C, Webster WW, Chen JH, Wilson SR, McClary A, Khan RM, Sobel N. Smelling a single component of male sweat alters levels of cortisol in women. J Neurosci (2007) 27:1261–1265.[Abstract/Free Full Text]

Yalom ID, Green R, Fisk N. Prenatal exposure to female hormones. Effect on psychosexual development in boys. Arch Gen Psychiatry (1973) 28:554–561.

Zald DH, Pardo JV. Functional neuroimaging of the olfactory system in humans. Int J Psychophysiol (2000) 36:165–181.

Zatorre RJ, Jones–Gotman M, Evans AC, Meyer E. Functional localization and lateralization of human olfactory cortex. Nature (1992) 360:339–340.

Zhou JN, Hofman MA, Gooren LJ, Swaab DF. A sex difference in the human brain and its relation to transsexuality. Nature (1995) 378:68–70.


jessie-c said...

Eugh, they quoted Blanchard and Bailey. And they used B&B's "Homosexual/nonhomosexual" model which is just plain wrong. That's going to cost them some points.

Nick K.D Chaleunphone said...

Again, that's just an unproven theory that has never been tested under scientific conditions to be proven valid. They come up with theory's, but don't come up with the results or proof. Their isn't any proof in the form of duplicating the work to see if it's a valid theory.

riki said...

Jessie - yes they utlise the pernicious Blanchard classification, but mainly to avoid any 'confounding factor' of sexual attraction to men.

Nick - have you read the Berglund article? It does not claim to be proof, but to be indicative. It does seem to have been done carefully and to qualify as good science. Unlike Swaab's research on the BSTc it should be realtively simple for another lab to replicate. I would agree that the "brain sex" etiological theory of transsexuality is not proven, but my extensive reading of the relevant literature suggests that it has more evidentiary support than other etiological theories - especially ones that focus on child raising psychological practices. Most likely is a hybrid model, with various sorts of biologically influenced predispositions interacting complexely with psychological and social expereinces.