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Research ArticleTheory/New Concepts, Cognition and Behavior

A New Theory of Gender Dysphoria Incorporating the Distress, Social Behavioral, and Body-Ownership Networks

Stephen V. Gliske
eNeuro 2 December 2019, 6 (6) ENEURO.0183-19.2019; https://doi.org/10.1523/ENEURO.0183-19.2019
Stephen V. Gliske
Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109
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    Figure 1.

    Networks related to key dimensions of gender dysphoria. Each box represents nuclei or brain regions involved in these networks. Red asterisks are included in boxes where the following regions/nuclei have known anatomic changes associated with transgender individuals (Smith et al., 2015; Guillamon et al., 2016; Altinay and Anand, 2019): anterior hypothalamus (AH; Garcia-Falgueras and Swaab, 2008); BNST (Zhou et al., 1995); anterior insula (aINS) and orbitofrontal cortex (OFC; Zubiaurre-Elorza et al., 2013); superior parietal lobe (SPL; Lin et al., 2014); and intraparietal sulcus (IPS; Case et al., 2017). Connections are based on the studies by Kong et al. (2010), Newman (1999), and Tillman et al. (2018). AH, Anterior hypothalamus; cAMY, central amygdala; DLPF, dorsolateral prefrontal cortex; LS, lateral septum; MCC, mid-cingulate cortex; mPOA, medial preoptic area; PAG, periaqueductal gray; Teg, tegmentum; VPM, ventral premotor cortex. Solid lines with arrows represent anatomical connections, while dash-dotted lines represent known functional connections.

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    Figure 2.

    Diagram of the multisense theory of gender dysphoria. The overall sense of gender in an individual is modeled as a neurobiological, reflective sense, integrating information from multiple senses and stimuli (bold arrows). This sense of gender is framed relative to gender assigned at birth (e.g., am I the gender that was assigned at birth?) rather than an absolute male/female dichotomy (e.g., am I female?). Each of the three listed reflexive senses (purple boxes) relate to a specific dimension of diagnostic criteria for gender dysphoria as well as a matching functional network with nodes known to be altered in transgender individuals (Fig 1). The interaction between sense of gender and these three reflexive senses may be bidirectional. External factors (green boxes) influence sense of gender either directly (bold arrow) or indirectly via affecting the reflexive senses. The model can also be extended to include additional internal and external factors. The diagram represents a dynamic network, not a specific causal pathway, and includes potentially complex interactions and feedback loops.

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eneuro: 6 (6)
eNeuro
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November/December 2019
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A New Theory of Gender Dysphoria Incorporating the Distress, Social Behavioral, and Body-Ownership Networks
Stephen V. Gliske
eNeuro 2 December 2019, 6 (6) ENEURO.0183-19.2019; DOI: 10.1523/ENEURO.0183-19.2019

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A New Theory of Gender Dysphoria Incorporating the Distress, Social Behavioral, and Body-Ownership Networks
Stephen V. Gliske
eNeuro 2 December 2019, 6 (6) ENEURO.0183-19.2019; DOI: 10.1523/ENEURO.0183-19.2019
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  • Article
    • Abstract
    • Significance Statement
    • Introduction
    • Background material
    • The new multisense theory of gender dysphoria
    • Discussion
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    • Footnotes
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Keywords

  • body-ownership network
  • distress
  • gender dysphoria
  • sensory perception
  • social behavioral network
  • transgender

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  • RE: Roepke
    Stephen V Gliske
    Published on: 05 May 2020
  • RE: Gliske 2019
    Troy A. Roepke
    Published on: 14 April 2020
  • Published on: (5 May 2020)
    Page navigation anchor for RE: Roepke
    RE: Roepke
    • Stephen V Gliske, Research Assistant Professor, Department of Neurology, University of Michigan

    Roepke (2020) present a critical reading of my recent paper (Gliske, 2019). I would like to address their concerns. Many of their points arise from misunderstandings of the paper, which I will now clarify, not actual weaknesses of the theory. While I apologize that the manuscript was not more clear to avoid these misunderstandings, it is important for scientific progress that these misconceptions are explained.

    One of the largest misconceptions by Roepke (2020) is that they feel the “implicit function of the paper is to explain the existence and ‘cause’ of transgender people,” claiming that the paper “attempts to pre-empt criticism by explicitly examining only gender dysphoria.” In fact, the reason I only explicitly examine gender dysphoria is because my intention was to only examine gender dysphoria. The extent to which my theory applies to transgender individuals is unknown and beyond the scope of this paper. The paper specifically stated “not all transgender individuals necessarily have gender dysphoria” (Gliske, 2019). Also, as Roepke (2020) pointed out, both cisgender and transgender people can experience gender dysphoria.

    Roepke (2020) defend their claim that I intended to discuss transgender individuals by stating: “Indeed, most of the citations consider transgender individuals rather than dysphoria as the subject of research. Importantly, Gliske (2019) ignores research which demonstrates that gender-conforming, cisgender individuals experience h...

    Show More

    Roepke (2020) present a critical reading of my recent paper (Gliske, 2019). I would like to address their concerns. Many of their points arise from misunderstandings of the paper, which I will now clarify, not actual weaknesses of the theory. While I apologize that the manuscript was not more clear to avoid these misunderstandings, it is important for scientific progress that these misconceptions are explained.

    One of the largest misconceptions by Roepke (2020) is that they feel the “implicit function of the paper is to explain the existence and ‘cause’ of transgender people,” claiming that the paper “attempts to pre-empt criticism by explicitly examining only gender dysphoria.” In fact, the reason I only explicitly examine gender dysphoria is because my intention was to only examine gender dysphoria. The extent to which my theory applies to transgender individuals is unknown and beyond the scope of this paper. The paper specifically stated “not all transgender individuals necessarily have gender dysphoria” (Gliske, 2019). Also, as Roepke (2020) pointed out, both cisgender and transgender people can experience gender dysphoria.

    Roepke (2020) defend their claim that I intended to discuss transgender individuals by stating: “Indeed, most of the citations consider transgender individuals rather than dysphoria as the subject of research. Importantly, Gliske (2019) ignores research which demonstrates that gender-conforming, cisgender individuals experience high rates of gender dysphoria...” Unfortunately, gender dysphoria did not receive its current definition until the DSM-V in 2013. A lot of neuroscience research about transgender individuals occurred before gender dysphoria was defined. These results are still informative of gender dysphoria because the incidence of gender dysphoria is much higher among transgender individuals than cisgender individuals. Contrary to the claim of Roepke (2020), my paper is consistent with the fact that conforming, cisgender individuals can have gender dysphoria. In fact, those individuals are one subpopulation that might be helped by any additional treatment options that come out of my theory. Still, use of data on transgender individuals to learn about gender dysphoria is valid, but projecting theories and treatments for gender dysphoria back to the full transgender population is not valid. This was not done in my paper.

    Unfortunately, Roepke (2020) then reinterpreted many of my statements about gender dysphoria as if they were meant to apply to transgender individuals, which leads to perception of flaws that are not supported by the text of the manuscript. For example, Roepke (2020) claims my paper starts with an “assumption that transgender modality (Ashley, 2021) constitutes a pathology.” In reality, the underlying assumption the paper starts with is that gender dysphoria is a pathology, as chronic, disabling distress related to one’s gender is not healthy, not for cisgender nor transgender individuals.

    Additionally, Roepke (2020) claim my paper attempts to “repair [transgender individuals] with conversion therapy.” The paper does not state this, but instead the removed clinical implications section was focused on mitigating the effect of gender dysphoria for all individuals, cisgender and transgender. It never suggested making a transgender individual not a transgender individual. Similarly, Roepke (2020) state my paper’s “silent thesis is that a trans person's lived experience of their gender is in fact an illusion resulting from otherwise unrelated neurological anomalies, or worse, abnormalities.” In actuality, the paper considers how neurological changes may impact perception of gender in only those individuals who have gender dysphoria.

    Another misrepresentation of Roepke (2020) is that the paper ignored the data on gender affirming treatment helping individuals with gender dysphoria. They also claim that these data are contrary to the predictions of my theory. Both of these claims are false and not supported by the text of the paper. These data were acknowledge in my paper and are the focus of the entire last paragraph of the “Comparison with other theories of gender dysphoria” section of the discussion. That section leads to one of the important predictions of the theory: that hormones given during gender-affirming therapy could influence one’s sense of gender and thus mitigate the symptoms of gender dysphoria. Data is now available that supports part of this prediction (Kilpatrick et al., 2019), though the reviewer notes from my paper’s first submission show that I did not know of those data until a reviewer pointed me to them.

    Another critique of Roepke (2020) is that “Literature on gender dysphoria should be used to back claims on gender dysphoria. Using literature on transgender individuals for this purpose risks conflating correlation and causation.” I agree with Roepke (2020), that the causation related to gender dysphoria cannot be determined from studies about transgender individuals. Thus, at present, the data support several theories about what the causation pathway actually is. The brain sex theory suggests one possible causal pathway, and my multisense theory suggests another. Only future data will be able to distinguish which theory is more applicable. Certainly, future studies on gender dysphoria should include both cisgender and transgender individuals and control for differences in these populations, as well as control for other factors noted in my paper.

    Roepke (2020) also expressed concern about the clinical implications section that was removed in the December, 2019 correction (eNeuro, 2019), by stating that the paper “espouse[s] harmful (now-retracted) clinical recommendations which lack any basis in clinical practice.” The only clinical recommendation was not meant to be interpreted as a recommendation to stop gender affirming treatment. Instead, it was meant to support that clinicians consider the multiple interpretations of existing data in order that all patients with gender dysphoria could be given a fully informed consent for the irreversible procedures. Being cautious is not “harmful,” but a way to minimize harm. The other text removed in the correction to the published article discussed possible, future implications if the theory was later proven true, but included no clinical recommendations to be taken at present. This section was removed as it was viewed as “too speculative” by eNeuro (2019).

    Another concern by Roepke (2020) was a claim that the paper “[p]roposes a hypothetical network (‘chronic distress processing network’) that is not described elsewhere in the literature (https://bit.ly/2ytZq8y), without offering compelling evidence for its existence.” I apologize that my use of wording led to the false conclusion that I proposed this network. Tillman et al. (2018) describe the extended amygdala network (EAc) and discussed its role in fear and anxiety. My labeling of the EAc as the “distress network” is consistent with their discussion of the existing literature and their findings, and I felt labeling it as I did would add clarity, whereas it seems to have caused confusion. I am sorry.

    Roepke (2020) also claim that the paper “[f]ails to develop a coherent theoretical model capable of making testable predictions.” I apologize that the testable predictions were not more clearly marked. Three of the main testable predictions implicit in the theory are:
    1. Whether the experience of distress in gender dysphoria is caused by or causes changes in the distress processing network (i.e., the EAc).
    2. Whether changes in the body ownership network cause or are caused by feelings of incongruence between body and identity.
    3. Whether hormones can mitigate distress or feelings of incongruence at doses lower than necessary for gender affirming treatment.

    A number of concerns stated by Roepke (2020) are lacking evidence or enough detail, and thus I am unable to address them. These include the following claims, that the paper
    “Misrepresents and makes claims unsupported by the cited animal and human literature.” It is unclear which claims were felt to be unsupported and which papers were felt to be misrepresented.
    “Neglects to acknowledge the body of literature describing the social decision-making network in humans...” The relevance to my paper is unclear, as there is no reason to believe that this network is altered in individuals with gender dysphoria.
    “Fails to meaningfully translate or contextualize results from animal studies when they were used to make claims about their human counterparts.” I need more information about which specific studies are being referred to.
    “Reveals motivated reasoning with a dissociation between the presented neurobiological evidence and the proposed behavioral-cognitive theory.” I am not certain what reasoning or dissociation is being referenced here. I can state my motive was to share an alternate way of looking at existing data, which if later proven true, could help many individuals with gender dysphoria.

    In conclusion, the scientific and ethical concerns made by Roepke (2020) are not substantiated. Therefore, their claim that my paper is “unethical and deserving of a full retraction” is also not supported. However, I do agree that my theory can be described as “a weighty claim that requires robust evidence” (Roepke, 2020). A theory is always based on existing data. The real “robust evidence” will be prospective data from future experiments that test which aspects of the theory are true and which are not. I look forward to such data.

    References

    eNeuro (2019) Correction: Gliske, “A New Theory of Gender Dysphoria Incorporating the Distress, Social Behavioral, and Body-Ownership Networks” eNeuro 2019, 6 (6); https://doi.org/10.1523/ENEURO.0513-19.2019

    Gliske SV. (2020) A New Theory of Gender Dysphoria Incorporating the Distress, Social Behavioral, and Body-Ownership Networks, eNeuro 2019, 6 (6); https://doi.org/10.1523/ENEURO.0183-19.2019.

    Kilpatrick LA, Holmberg M, Manzouri A, Savic I (2019) Cross sex hormone treatment is linked with a reversal of cerebral patterns associated with gender dysphoria to the baseline of cisgender controls. Eur J Neurosci. 50:3269–3281. https://doi.org/10.1111/ejn.14420

    Roepke TA (2020) RE: Gliske (electronic response to Gliske SV (2019) A New Theory of Gender Dysphoria Incorporating the Distress, Social Behavioral, and Body-Ownership Networks. eNeuro 2019 6 (6); https://doi.org/10.1523/ENEURO.0183-19.2019)

    Tillman, RM, Stockbridge MD, Nacewicz BM, Torrisi S, Fox AS, Smith JF, Shackman AJ (2018) Intrinsic functional connectivity of the central extended amygdala. Hum Brain Mapp. 39:1291–1312. https://doi.org/10.1002/hbm.23917

    Show Less
    Competing Interests: None declared.
  • Published on: (14 April 2020)
    Page navigation anchor for RE: Gliske 2019
    RE: Gliske 2019
    • Troy A. Roepke, Associate Professor, Rutgers, The State University of New Jersey

    The neuroscience underlying gender identity remains a controversial topic and a legitimate subject of scientific inquiry. However, Gliske (2019) contains scientific errors and unacknowledged ethical consequences. Rather than developing hypotheses for the neuroscience of gender based on a dispassionate review of the evidence, Gliske (2019) reverses the scientific method and starts with an assumption that transgender modality (Ashley, 2021) constitutes a pathology. Gliske (2019) forces a selective reading of available data to espouse harmful (now-retracted) clinical recommendations which lack any basis in clinical practice. As a result, its silent thesis is that a trans person's lived experience of their gender is in fact an illusion resulting from otherwise unrelated neurological anomalies, or worse, abnormalities. This is a weighty claim that requires robust evidence.

    Below we outline the specific scientific issues in Gliske (2019) that we will address further in a forthcoming manuscript (in prep.). Gliske (2019):

    ● Misrepresents and makes claims unsupported by the cited animal and human literature.
    ● Neglects to acknowledge the body of literature describing the social decision-making network in humans.
    ● Fails to meaningfully translate or contextualize results from animal studies when they were used to make claims about their human counterparts.
    ● Proposes a hypothetical network (“chronic distress processing network”) that is not desc...

    Show More

    The neuroscience underlying gender identity remains a controversial topic and a legitimate subject of scientific inquiry. However, Gliske (2019) contains scientific errors and unacknowledged ethical consequences. Rather than developing hypotheses for the neuroscience of gender based on a dispassionate review of the evidence, Gliske (2019) reverses the scientific method and starts with an assumption that transgender modality (Ashley, 2021) constitutes a pathology. Gliske (2019) forces a selective reading of available data to espouse harmful (now-retracted) clinical recommendations which lack any basis in clinical practice. As a result, its silent thesis is that a trans person's lived experience of their gender is in fact an illusion resulting from otherwise unrelated neurological anomalies, or worse, abnormalities. This is a weighty claim that requires robust evidence.

    Below we outline the specific scientific issues in Gliske (2019) that we will address further in a forthcoming manuscript (in prep.). Gliske (2019):

    ● Misrepresents and makes claims unsupported by the cited animal and human literature.
    ● Neglects to acknowledge the body of literature describing the social decision-making network in humans.
    ● Fails to meaningfully translate or contextualize results from animal studies when they were used to make claims about their human counterparts.
    ● Proposes a hypothetical network (“chronic distress processing network”) that is not described elsewhere in the literature (https://bit.ly/2ytZq8y), without offering compelling evidence for its existence.
    ● Fails to develop a coherent theoretical model capable of making testable predictions.
    ● Makes predictions from the model presented which conflict with existing empirical observations, e.g., alleviation of gender dysphoria with gender-affirming intervention (Murad et al., 2010; Olson et al., 2016; Serano, 2007)
    ● Reveals motivated reasoning with a dissociation between the presented neurobiological evidence and the proposed behavioral-cognitive theory.

    Gliske (2019) attempts to pre-empt criticism by explicitly examining only gender dysphoria; nevertheless, the implicit function of the paper is to explain the existence and “cause” of transgender people. Indeed, most of the citations consider transgender individuals rather than dysphoria as the subject of research. Importantly, Gliske (2019) ignores research which demonstrates that gender-conforming, cisgender individuals experience high rates of gender dysphoria (Joel et al., 2014; Watt & Einstein, 2016) and that gender dysphoria in transgender individuals is reduced or eliminated by transitioning (Murad et al., 2010; Olson et al., 2016; Serano, 2007). Literature on gender dysphoria should be used to back claims on gender dysphoria. Using literature on transgender individuals for this purpose risks conflating correlation and causation.

    Gliske (2019) demonstrates the risk inherent in human research that fails to sufficiently engage with the community under study. Starting from the assumption that transgender modalities (Ashley, 2021) are a deviation from an unexamined norm leads inevitably to the harmful idea that trans people can and should be subjected to attempts to “repair” them with conversion therapy.

    Scientific and methodological issues notwithstanding, Gliske (2019) would remain unethical and deserving of a full retraction. The now-withdrawn section on clinical implications exemplifies an approach to science unconcerned with the real-world consequences for the lives of marginalized people. Rather than pathologizing transgender modalities as exceptions to cisgender modalities, studying the neurobiology of gender requires operationalizing the existence of gender itself.

    Signed,
    Elizabeth A Aulino, BS, Doctoral Candidate, Kent State University, eaulino{at}kent.edu
    Avery R Everhart, MA, Doctoral Candidate, Population, Health, & Place Program, Spatial Sciences Institute, University of Southern California, everhart{at}usc.edu
    Sofia Kirke Forslund, PhD, Junior Group Leader, Experimental and Clinical Research Centre (joint venture of Charité University Hospital and the Max Delbrück Centre for Molecular Medicine), Sofia.Forslund{at}mdc-berlin.de
    Olivia Guest, PhD, Research Scientist, RISE, Nicosia, Cyprus and Department of Experimental Psychology, University College London, London, UK, o.guest{at}ucl.ac.uk
    E Mae Guthman, PhD, Postdoctoral Research Associate, Princeton Neuroscience Institute, Princeton University, eguthman{at}princeton.edu
    Troy A Roepke, PhD, Associate Professor, Rutgers University, ta.roepke{at}rutgers.edu
    Jonny Saunders, MSc, Doctoral Student, Institute of Neuroscience, University of Oregon, jsaunder{at}uoregon.edu
    Simón(e) D Sun, MSc, Doctoral Candidate, Center for Neural Science, New York University, sds553{at}nyu.edu
    Reubs J Walsh, BA (Oxon), MSc (Lond), Promovendus, Department of Clinical, Neuro- and Developmental Psychology, Vrije Universiteit, r.j.walsh{at}vu.nl

    The signatories have no competing financial interests.

    REFERENCES:
    Ashley F (2021) ‘Trans’ is my gender modality: A modest terminological proposal. In: Trans Bodies, Trans Selves, 2nd ed (Erickson-Schroth L ed), Oxford University Press (In press). https://www.florenceashley.com/uploads/1/2/4/4/124439164/florence_ashley...

    Murad MH, Elamin MB, Garcia MZ, Mullan RJ, Murad A, Erwin PJ, Montori VM (2010). Hormonal and sex reassignment: A systematic review and meta-analysis of quality of life and pyschosocial outcomes. Clinical Endocrinology, 72: 214-231. doi: 10.1111/j.1365-2265.2009.03625.x
    Olson KR, Durwood L, DeMeules M, & McLaughlin KA (2016) Mental health of transgender children who are supported in their identities. Pediatrics, 137: 1–8. Doi: 10.1542/peds.2015-3223
    Joel D, Tarrasch R, Berman Z, Mukamel M, Ziv E (2014). Queering gender: Studying gender identity in normative individuals. Psychology Sexuality 5: 291321. doi: 10.1080/19419899.2013.830640

    Serano J (2007) Whipping Girl. Seal Press.

    Watt S, Einstein G (2016) Beyond the binary: The corporeal lives of trans individuals. In: Transsexuality in theology and neurosciences: Findings, controversies, and perspectives (Schreiber G ed), p 5371. Walter de Gruyter.

    Show Less
    Competing Interests: None declared.

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