1. The Effect of Fraternal Birth Order on Motor Coordination: Developing a Model for Autism, Attention Deficit/Hyperactivity Disorder, and Dyslexia Allison Shaw and S. Marc Breedlove, Ph.D., Neuroscience Program and Department of Psychology, Michigan State University, East Lansing, MI 48824 Background Purpose Methods (Cont’d) Results Acknowledgements Current/Future Research References Neurodevelopmental Disorders are a broad class of psychiatric disorders where symptoms begin to appear early in development. Vincent et al. 1 (2002) and Dalton et al. 2 (2003) posit that some neurodevelopmental disorders (autism and dyslexia) may be caused by a process by which antibodies that transfer through the placenta to the fetus and affect development, known as the maternal immune transfer. Similarly, Blanchard & Bogaert (1996) suggest that fraternal birth order may effect fetal development in a similar maternal transfer, maternal immune hypothesis, which they believe signals an increased androgen release. Autism (Cohen-Baron, unpub.) and Dyslexia (Caspi, unpub.) have a fraternal birth order effect. Males with Attention Deficit/Hyperactivity Disorder (inattention) have been shown to be hypermasculinized in finger ratio lengths due to prenatal androgens, as suggested by the maternal immune hypothesis (McFadden, in press). Individuals with these disorders have decreased motor coordination ranging from inability to control movement to deficiencies in fine motor movement. This is the first study to control the birth order of mice in order to develop a model that will examine the etiology of Autism, Dyslexia, and Attention Deficit/Hyperactivity Disorder. Subjects n=110 Green Fluorescent Protein (GFP) transgenic mice 61 males 25 with older brothers, 36 with older sisters 49 females 20 with older brothers, 29 with older sisters Imagine 1: Green Fluorescent Protein (GFP) transgenic mice were breed at Van Andel. Male mice carry a recessive protein marker on their DNA that allows them to glow when exposed to UV light. This allows for prenatal sexing of mice. EffectFHypothesis dfError dfSig. Weight2.4251010.041 Older Siblings1.2451010.296 Sex0.2251010.959 Older Siblings * Sex1.4551010.212 EffectFHypothesis dfError dfSig. Weight0.7651010.583 Older Siblings0.3851010.862 Sex1.0451010.399 Older Siblings * Sex2.0251010.082 Table 1: Rotation Times Table 2: Transit Times Table 1 shows two-way ANOVA analysis that yields no significant effects of sex and older siblings on Static Rod rotation times. Table 2 displays results of two-way ANOVA analysis that yields a marginal effect of sex and older sibling on Static Rod transit times. Post-Hoc Multivariate General Linear Model on Transit Times Rod 2: 25.6mm Rod 5: 9.4mm Conclusions 1 Vincent, A., Deacon, R., Dalton, P., Salmond, C., Blamire, A.M., Pendlebury, S., Johansen-Berg, H., Rajogopalan, B., Styles, P., & Stein, J. (2002) Maternal antibody-mediated dyslexia? Evidence for a pathogenic serum factor in a mother of two dyslexic children shown by transfer to mice using behavioral studies and magnetic resonance spectroscopy. Journal of Neuroimmunology, 130, 243-247. 2 Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., Styles, P., & Vincent, A. (2003) Maternal neuronal antibodies associated with autism and a language disorder. Annual Neurology, 53, 533-537. 3 Blanchard, R. (2001) Fraternal birth order and the maternal immune hypothesis of male homosexuality. Hormone and Behavior, 40, 105-114. Since there exists a marginal difference on transit times when looking at sex and older sibling, a post-hoc test was used to analyze a linear model on transit times for each rod. The initial results suggest that older sibling may affect each sex differently. The multivariate general linear model shows that in fact depending on the sex, older sibling will affect transit times differently. The difference between how older siblings affected each sex approached significant on Rod 1 (p<.1) and is significant on Rod 4 (p<.05). * p<.1 ** p<.05 Although it does not appear that fraternal birth order affect motor coordination, when post-hoc analyzes are run, significant interactions exist. The sex of older siblings affects each sex differently and that difference is significant on Rods 1 and 4. There may exist a significant difference on Rod 1, not necessarily because of motor coordination, but rather due to motivation and understanding of the task. It may have taken male mice with older brothers longer to figure out the task. However, by the time mice are tested on Rod 4, they should have learned the task and be motivated to traverse the rod. Thus, Rod 4, because it is so thin, tests motor coordination better than the three previous rods and the differences that we see on Rod 4 are more likely due to differences in motor coordination. One note of interests is that females seem to be affected by fraternal birth order, as well, which is inconsistent with much of the research done in humans. Current cohort of mice have been tested on a Gap Detection Paradigm. This test mimics that of tests administered to humans that are used to diagnose dyslexic individuals. Those with dyslexia have a difficult time with auditory processing. Results of that test have found that males with older brothers have a more difficult time detecting gaps in tones than mice with older sisters; however, female mice seem not to be affected either way. Also, these mice have been tested in an Open Field Object Recognition and Novelty test. This paradigm will allow us to conclude whether or not fraternal birth order has an effect on object recognition. Individuals with autism have a difficult time with social and object recognition. Future tests include, but not limited to, Olfactory Recognition, partner preference, and sexual behaviors. Furthermore, a new cohort of mice will be breed in order to better control for variability. In addition to mouse model research, research done on humans will be included. Male/Female twins will be used in order to further explore why female mice might be affected by fraternal birth order. Fraternal birth order may not affect females, but rather her male littermates who in turn affect their sister. Thanks to: Breedlove/Jordan Lab, especially Janice Wong, Dave Putz, and Lace Svec for all their help McNair/SROP staff, especially Nettavia Curry, Roop Jayaraman, and Bethany Best Natural Science Methods Class This research project was funded by NIH grant MH58703 Rod 1* : 31.1mm Rod 3: 19.5mm Rod 4**: 15.4mm Behavioral Test (Static Rod) Mice were tested on five static rods (69.5mm length), which decreased in diameter (31.1, 25.6, 19.5, 15.4, 9.4mm), in order to assess motor coordination. Each mouse was placed with their nose facing the end of the rod. The duration it took the mouse to turn 180 degrees (rotate) and the time it took for the mouse’s nose to cross a predetermined mark 10cm from the wall (transit) were recorded. Mice were allowed to attempt both behaviors for up to three minutes (180 seconds). If the mouse fell off of the static rod, then they were given a default time of 180 seconds. Methods Individuals with these disorders have decreased motor coordination ranging from inability to control movement to deficiencies in fine motor movement. Maternal Response Androgen Signaling Developmental Differences