Sunday, November 9, 2014

On the Fluidity of Gender as “Normal”– A Case Against Traditional Gender Categories in Psychology and Neuroscience Research

Psychology and neuroscience have always been concerned with anomalies. Whether this means studying a small population with a rare disease, or teasing apart seemingly trivial differences in behavior, human experience that deviates from accepted norms is rife with potential for scientific understanding and progress. This notion is relevant in psychological and neuroscientific pursuits of gendered differences in behavior and brain function. The terms gender and sex have been used interchangeably in much scientific literature. In reality, the two mean quite different things: The term sex indicates an assignment of male or female at birth, based on biological norms and expectations. The term gender, on the other hand, is distinctive from sex in that it does not necessitate congruence with sex. Gender is the identity which one feels or claims, often male or female, and exists independently from biological, assigned sex.
Historically, the gender binary has been comprised of male and female. These two categories have often been presented as exclusive and opposing. In the fields of psychology and neuroscience, much research has relied on the categories of male and female as separate and distinct. Even when sex and gender are recognized as separate, as in the case of transgender persons, for example, people are categorized as either men or women. Study participants have largely been classified as either male or female with no alternative or expanded option. This mimics the norm of the gender binary in western society today. Society allots little room for deviance from the gender binary and expectations of masculinity and femininity that accompany it. Gender nonconformity is regularly treated as an abnormality affecting a very small minority of the population. Psychology and neuroscience research that relies on the gender binary for interpretation and meaning of scientific findings would need to be reassessed if, perhaps, the gender binary is not as solid as society would like it to be.
Research conducted by Joel et al. (2013) supports the deconstruction of the gender binary based on their findings that point to a more fluid and elastic experience of gender than the male/female binary allows for. Importantly, their research challenges the myth that gender nonconformance is a rare occurrence in typical populations. Joel et al. (2013) developed a novel questionnaire that measures multiple facets of gender identity in ways which prior psychology research had not. As illustrated in Figure 1 below, there was extensive overlap in the experiences of male and female identified participants in regards to their gender and whether or not they felt “as a man” or “as a woman” (Joel et al. 2013). It is key to note that participants in normative male and female categories showed a wide spread of responses as to whether or not they felt as a man or as a woman.



These findings do indeed indicate that gender is much more fluid than the male/female binary allows. Thus, Psychology and Neuroscience need to account for that fluidity both in future research but also in reassessing the soundness of prior research that relied on the male/female dichotomy for meaning. Furthermore, it is important for research to expressly solicit information on gender identity and gender sentiment versus relying on stereotypical external cues to gather the gender of a participant based on researchers’ assumptions. This is particularly important when it comes to research on transgender persons. The research from Joel et al. (2013) also challenges the distance felt from trans* related research based on the conceptions that transgender experience is a seemingly distant “ism” and that gender nonconformity supposedly only affects a small percentage of the population. “Stable” gender categories are, in reality, not very stable. Given the findings from Joel et al. (2013), it is also interesting to consider how gendered findings from animal research in psychology and neuroscience should be interpreted. One last point – this piece is not meant to question the validity of anyone’s gender identity, rather it is meant to question the commonly accepted and propagated notions of male and female as separate and exclusive categories.


 References
Joel, D., Tarrasch, R., Berman, Z., Mukamel, M., & Ziv, E. (2013). 
Queering gender: Studying gender identity in ‘normative’ individuals. Psychology & Sexuality, 5:4, 291-321.

The Effect of Sex Differences on Brain Stimulation

A recent development in the world of neuroscience has been the rise of a technology called Brain Stimulation. Although some stimulation technologies have existed for a long time (deep brain stimulation to treat Parkinson’s), a recent wave of cheap, available stimulation technologies have provided a myriad of interesting possibilities for treatment of diseases, cognitive enhancement, and human brain research. Brain stimulation has been shown to confer all sorts of effects, from increased motor skill, better memory, stronger visual acuity, better concentration, and many others. Brain stimulation can be accomplished via many methods, including transcranial magnetic stimulation (TMS), transcranial pulsed ultrasonic stimulation (TPU), microelectrode array stimulation and deep brain stimulation. Although these technologies have many benefits (accessibility, academic validity, accuracy), transcranial direct current stimulation (tDCS) is best situated with a balance of price, accuracy, evidence, and accessibility. This has elicited an enormous amount of interest from researchers and the public alike .

tDCS is a technology that uses small amounts of voltage with low direct current to slightly raise the base level of depolarization (anodal stimulation) or hyperpolarization (cathodal stimulation) at the neuronal level of a specific area of cortex. Research seems to suggest that anodal stimulation increases activity, whereas cathode stimulation decreases activity. This could be crucial in replicating or promoting desired brain states, as many brain states rely on deactivation as well as activation. Side effects of the technology depend on the individual and range from small headaches to tingling across the scalp. Because of the mechanisms involved in a neural action potential, raising the level of depolarization, tDCS effectively lowers the threshold needed to fire a neural message. Therefore, any cortical area stimulated with tDCS will see higher rates of activation than normal. It is important to note that tDCS does not elicit activation. Rather, it amplifies the tendencies that already exist within the brain for individual neurons to fire. Other brain stimulation methods such as TMS or TPU induce activation that is not generated via natural depolarization or hyperpolarization, which makes tDCS that much more attractive. Via plasticity mechanisms such as long-term potentiation, tDCS can enhance activation patterns and strengthen neural pathways much faster than normal mechanisms. tDCS has a short-term effect on the brain, and suggest that it achieves its effects through use-dependent synaptic plasticity (Demirtas-Tatlidede, 2013). This amplification or depressing effect has enormous potential, especially when applied to a training context.

Questions may be raised, however, of the different effects that tDCS may have males and females. There is a large body of literature suggesting that sex differences exist in the brain; it follows that tDCS may have different effects in areas of the brain where sex plays an important role in differentiation. There is evidence to suggest that certain types of stimulation work better in women than in men, specifically in the motor cortex stimulation, a main area of tDCS research and applications. Nitsche et al. state that cathodal stimulation is more effective than anodal stimulation in women, but it is the opposite in men. Anodal stimulation, on the other hand, is more effective in stimulating the visual cortex of brain (Nitsche et al., 2008). Chaieb, Antal, & Paulus, (2008) examined the effectiveness of tDCS in different genders as well; they found that women responded extremely well to anodal stimulation, and its effects persisted at least 10 minutes after stimulation. Conversely, men experienced a dampened activation effect in the same brain area with the same stimulation.





The attached figure from Chaieb et al. shows clear differences between men and women for the persistence of tDCS effects. On the left half of the figure, cathodal stimulation produced similar effects in both the male and female groups; on the right half, a significant difference is shown from 0 minutes after stimulation to 10 minutes after stimulation.

These effects have significant implications for the future of brain stimulation; the results presented in the current studies suggest that women may be more susceptible to brain stimulation. This is most likely caused by increased plasticity in the brain, allowing for the stimulation to take on a greater effect. By maintaining a high level of plasticity and being sensitive to brain changes, women may benefit more from external training and stimulation tools such as tDCS. Men, however, may need additional therapy or stimulation to attain the same effects. Based on the presented works, considerations should be made for different gender groups when conducting experiments with tDCS, and eventual applications of the technology should be aware of its different effects on males and females alike.


References
Chaieb, L., Antal, A., & Paulus, W. (2008). Gender-specific modulation of short-term neuroplasticity in the visual cortex induced by transcranial direct current stimulation. Visual neuroscience, 25(01), 77-81.
Demirtas-Tatlidede, A., Vahabzadeh-Hagh, A. M., & Pascual-Leone, A. (2013). Can noninvasive brain stimulation enhance cognition in neuropsychiatric disorders?. Neuropharmacology, 64, 566-578.
de Tommaso, M., Invitto, S., Ricci, K., Lucchese, V., Delussi, M., Quattromini, P., ... & Cicinelli, E. (2014). Effects of anodal TDCS stimulation of left parietal cortex on visual spatial attention tasks in men and women across menstrual cycle. Neuroscience letters, 574, 21-25.
Fitz, N. S. & Reiner, P. B. (2013). The challenge of crafting policy for do-it-yourself brain stimulation. J Med Ethics. doi:10.1136/medethics-2013-101458
Keshvari, F., Pouretemad, H. R., & Ekhtiari, H. (2013). The effect of gender on dorsolateral prefrontal cortex transcranial DC stimulation-induced disruption of moral judgment. Advances in Cognitive Science, 14(456), 1-12.
Kuo, M. F., Paulus, W., & Nitsche, M. A. (2006). Sex differences in cortical neuroplasticity in humans. Neuroreport, 17(16), 1703-1707.
Lapenta, O. M., Fregni, F., Oberman, L. M., & Boggio, P. S. (2012). Bilateral temporal cortex transcranial direct current stimulation worsens male performance in a multisensory integration task. Neuroscience Letters, 527(2)

Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., ... & Pascual-Leone, A. (2008). Transcranial direct current stimulation: state of the art 2008. Brain Stimulation, 1(3), 206-223.

Understanding Depression: An Interplay of Culture and Biology

Although both sexes suffer from depression, women are more likely to suffer from depression and in fact, women are twice as likely as men to develop major depressive disorder (MDD) (Guilloux et al. 2012). This sex difference is not unique to the United States but has been observed across countries ranging from high to low gender equity and economic development (Hopcroft and Bradley 2007). Researchers have continued to search for a biological mechanism that can explain a potential predisposition for depression in women but a consensus has yet to be reached. This failure to identify such a cause might be due in part to the potential existence of multiple factors. Furthermore, one may not be able to explain depression solely from a biological perspective; evidence suggests that cultural studies of depression are also important in understanding the disorder. A sociological position on illness could therefore also prove useful.

GABA interneuron related peptides, like neuropeptide Y (NPY), and other signaling molecules in the brain are among the possible genetic factors linked to a predisposition to depression. NPY, a neurotransmitter found in the brain and autonomic nervous system is thought to play a role in anxiety and stress, blood pressure, and fat storage (Gilloux et al 2012; Zhou et al. 2008). A study by Gilloux et al. (2012) focused on a section of the amygdala, a brain structure, which is associated with the regulation of emotion. In post-mortem evaluations of subjects with major depressive disorder, all of who were female, they noted a significant downregulation for the genes that encode for these signaling molecules such as NPY. With evidence that these peptides might play a role in MDD, they then looked to mouse models of depression. In their experiments, they found a similar decreased function of NPY (Gilloux et al. 2012). Thus, lower levels of NPY and related GABA neuron peptides could lead to a greater chance of developing depression. Finally, they compared these observations with similar work previously performed in male mice. This earlier study showed a less pronounced downregulation of the genes of interest, resulting in higher levels of NPY, which might help to explain this sex difference between males and females.


However, as already noted, this biological explanation might not be sufficient in understanding this unequal distribution. Other factors, such as socioeconomic status and even cultural factors within the home, also seem to play a large role in one’s chance of developing depression. These cultural forces are likely to affect one’s stress and anxiety, which could, in turn trigger depression. One study performed by Hopcraft and Bradley surveyed males and females across 29 countries on matters such as employment, marriage status, self efficacy and religion, which can all impact one’s mental wellness. In all countries, they noted that females were significantly more depressed than males (Hopcraft and Bradley 2007). To compare between groups of females, they examined each country’s Gender-related Development Index (GDI). GDI is a measurement of gender gap in regards to health, education and command of economic resources. As the study found, those in countries with a high GDI, were less likely to be depressed than those in countries with a low GDI.

Fig 1. Probability of depression by age and sex. Men and women are grouped by high or low GDI.

As the graph shows, men in countries with a high GDI were less depressed than men in countries with a low GDI. Research has suggested that everyday life is more taxing in less developed societies due to the greater threat of war, poverty, disease and social unrest to explain this phenomena. Both groups of males, however, fell below female scores for depression. Some researchers propose that males benefit from their social standing in society, resulting in the gender gap. While females may find themselves impacted from the same issues of disease and social unrest as men, males still find that they have greater self efficacy and freedom of choice, which would improve their quality of life (Hopcraft and Bradley 2007; Rosenfield 1980).

Ultimately, it is difficult to say which plays a greater role in this sex difference in depression – cultural or biological factors. Although it is appealing to pinpoint a particular biological pathway to treat, it is likely the case that society and biology are both pertinent and so neither can be discounted when considering the issue.

References
Guilloux J, Douillard-Guilloux G, Kota R, Wang X, Gardier AM et al. (2012). Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Molecular Psychiatry 17: 1130-1142
Hopcraft RL and Bradley DB. (2007). The sex difference in depression across 29 countries. Social Forces 85(4): 1483-1507.
Rosenfield S. (1980). Sex differences in depression: do women always have higher rates? Journal of  Health and Social Behavior 21(1): 33-42.
Zhou Z, Zhu G, Hariri AR, Enoch M, Scott D et al. (2008). Genetic variation in human NPY expression affects stress response and emotion. Nature 452: 997-1002.