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The developmental origins of autism spectrum disorder: the 2D:4D digit ratio as biomarker
S724
P.7.b. Child and adolescent disorders and treatment − Disorders (clinical)
Results: Relative to CD/CU− and HC youths, CD/CU+ youth showed abnormally increased BLA connectivity with a cluster that included both dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices, along with posterior cingulate, sensory associative, and striatal regions. In contrast, compared to CD/CU− and HC youths, CD/CU+ youths showed diminished CMA connectivity with the ventromedial/orbitofrontal region. Critically, these connectivity changes in CD/CU+ participants coincided with local hypotrophy of BLA and CMA subregions, and were associated to more severe CU symptoms. Conclusions: In summary, juvenile offenders with CD/CU+ showed functionally disorganized amygdala networks, which were accompanied by amygdala structural defects. These findings provide unique insights into a putative mechanism for perturbed attention-emotion interactions, which could bias salience processing and associative learning in youth with CD/CU+. The findings represent an important step towards characterizing the neurocircuitry of conduct disorder with psychopathic traits, and may as such inform the development of reliable biomarkers and potential therapeutic targets. References [1] Frick, P.J., Viding, E., 2009. Antisocial behavior from a developmental psychopathology perspective. Developmental Psychopathology 21, 1111–1131. [2] Anderson, N.E., Kiehl, K.A., 2014. Psychopathy: Developmental perspectives and their implications for treatment. Restorative Neurology and Neuroscience 32, 103–117. [3] Moul, C., Killcross, S., Dadds, M.R., 2012. A model of differential amygdala activation in psychopathy. Psychological Review 119, 789– 806.
P.7.b.019 The developmental origins of autism spectrum disorder: the 2D:4D digit ratio as biomarker M. Mackus1 ° , D. De Kruijff1 , L.S. Otten1 , J. Garssen1,2 , J.C. Verster1,3 1 Utrecht University, Division of Pharmacology, Utrecht, The Netherlands; 2 Nutricia Research, Utrecht, The Netherlands; 3 Swinburne University, Centre for Human Psychopharmacology, Melbourne, Australia Introduction: Autism spectrum disorder (ASD) is identified as a sexually dimorphic disorder, meaning that it may be influenced by fetal levels of testosterone and estrogen [1]. As described by several studies, levels of prenatal sex hormones can be related to the digit ratio of the index (2D) and ring (4D) finger [2]. It has been known that males tend to have longer fourth digits relative to second digits than females, indicating higher levels of fetal testosterone in comparison to estrogen in males [2]. As the development of the central nervous system (CNS) is also influenced by prenatal sex hormones, it has been suggested that the 2D:4D digit ratio may be a biomarker for the risk of developing CNS diseases such as autism. One study found that N = 72 children diagnosed with autism had lower 2D:4D digit ratios when compared to age-matched healthy controls [3], and a 2012 meta-analysis confirmed that adults with autism tend to have a lower 2D:4D digit ratio [4]. However, recent studies could not replicate these findings [5]. Aim(s) of the study: To determine the usefulness of the 2D:4D digit ratio as biomarker for autism spectrum disorder. Methods: Participants were recruited among students from Utrecht University. For both hands, digit lengths of the second (2D, index finger) and fourth (4D, ring finger) finger were measured
using digital Vernier calipers recording to 0.01 mm. In addition to demographics, the Autism Spectrum Quotient (AQ) questionnaire was completed. The AQ is divided into four subscales, each assessing a different aspect of ASD. The subscales comprise ‘social insights and behavior’, ‘difficulties with change’, ‘communication’, ‘phantasy and imagination’, and ‘detail orientation’. Using correlational analyses, the relationship between the 2D:4D digit ratio and the overall AQ scores and those of its subscales was computed. Results of participants with dove-type personality (2D:4D >1.00) were compared to those with a hawk-type personality (2D:4D <1.00). Analyses were also conducted for men and women separately. Results: N = 271 healthy volunteers with an average age of 29 years old participated in the study. 54.2% of the participants were women, 45.8% were men. Overall, no significant correlations were observed between the AQ total score and its subscales and the 2D:4D digit ratio. For women, also no significant correlations were found. For men, a significant correlation was found between the left 2D:4D digit ratio and the AQ subscale ‘difficulties with change’ (r = 0.189; p = 0.038). There was no significant difference between dove-type and hawk-type participants on any of the AQ subscales, nor with the total AQ score. Conclusions: In contrast to previous research, we did not find a significant association between the 2D:4D digit ratio and autism spectrum disorder scores. Although our data suggests that the 2D:4D digit ratio is not a suitable biomarker to identify individuals with an increased risk of having autism spectrum disorder, it should be taken into account that we investigated a nonclinical healthy student sample. Future studies should be conducted in patients that are formally diagnosed with autism. References [1] Davis, P.D., Pfaff, D., 2014. Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder. Psychoneuroendocrinology. 49, 11−25. [2] Manning J., Kilduff L., Cook C., Crewther B., Fink B., 2014. Digit ratio (2D:4D): A biomarker for prenatal sex steroids and adult sex steroids in challenge situations. 30, 5−9. [3] Manning J.T., Baron-Cohen S., Wheelwright S., Sanders G., 2001. The 2nd and 4th digit ratio and autism. Dev Med Child Neurol. 43, 160−4. [4] H¨onekopp, J., 2012. Digit ratio 2D:4D in relation to autism spectrum disorders, empathizing, and systemizing: a quantitative review. Autism Res, 5, 221−30. [5] Guyatt, A.L., Heron, J., Knight, Ble C., Golding, J., Rai, D., 2015. Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study. BMJ open. 5, e007433. Disclosure statement: This research was supported by Utrecht University. Joris Verster has received grants / research support from The Dutch Ministry of Infrastructure and the Environment, Janssen Research and Development, Nutricia, Takeda, Red Bull, and has acted as a consultant for Canadian Beverage Association, Centraal Bureau Drogisterijbedrijven, Coleman Frost, Danone, Deenox, Eisai, Janssen, Jazz, Purdue, Red Bull, Sanofi-Aventis, Sepracor, Takeda, Transcept, Trimbos Institute, and Vital Beverages. Johan Garssen is part-time employee of Nutricia.
P.7.b.020 Psychiatric disorders associated to incontinentia pigmenti: two case reports L. Espinosa1 ° , A. Fortea1 , I. Dom´ınguez1 , I. Molinero2 , A. Morer3 , I. Baeza3 , G. Sugranyes3 1 Hospital Clinic De Barcelona, Psychiatry, Barcelona, Spain; 2 Hospital Santa Maria, Psychiatry, Lleida, Spain; 3 Hospital Clinic De Barcelona, Child and Adolescent Psychiatry, Barcelona, Spain Introduction: Incontinentia pigmenti (IP) is a rare X-linked dominant syndrome (incidence 0.0025%) which manifests with skin, teeth, ocular and neurological abnormalities, that usually
P.7.b. Child and adolescent disorders and treatment − Disorders (clinical)
Results: Relative to CD/CU− and HC youths, CD/CU+ youth showed abnormally increased BLA connectivity with a cluster that included both dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices, along with posterior cingulate, sensory associative, and striatal regions. In contrast, compared to CD/CU− and HC youths, CD/CU+ youths showed diminished CMA connectivity with the ventromedial/orbitofrontal region. Critically, these connectivity changes in CD/CU+ participants coincided with local hypotrophy of BLA and CMA subregions, and were associated to more severe CU symptoms. Conclusions: In summary, juvenile offenders with CD/CU+ showed functionally disorganized amygdala networks, which were accompanied by amygdala structural defects. These findings provide unique insights into a putative mechanism for perturbed attention-emotion interactions, which could bias salience processing and associative learning in youth with CD/CU+. The findings represent an important step towards characterizing the neurocircuitry of conduct disorder with psychopathic traits, and may as such inform the development of reliable biomarkers and potential therapeutic targets. References [1] Frick, P.J., Viding, E., 2009. Antisocial behavior from a developmental psychopathology perspective. Developmental Psychopathology 21, 1111–1131. [2] Anderson, N.E., Kiehl, K.A., 2014. Psychopathy: Developmental perspectives and their implications for treatment. Restorative Neurology and Neuroscience 32, 103–117. [3] Moul, C., Killcross, S., Dadds, M.R., 2012. A model of differential amygdala activation in psychopathy. Psychological Review 119, 789– 806.
P.7.b.019 The developmental origins of autism spectrum disorder: the 2D:4D digit ratio as biomarker M. Mackus1 ° , D. De Kruijff1 , L.S. Otten1 , J. Garssen1,2 , J.C. Verster1,3 1 Utrecht University, Division of Pharmacology, Utrecht, The Netherlands; 2 Nutricia Research, Utrecht, The Netherlands; 3 Swinburne University, Centre for Human Psychopharmacology, Melbourne, Australia Introduction: Autism spectrum disorder (ASD) is identified as a sexually dimorphic disorder, meaning that it may be influenced by fetal levels of testosterone and estrogen [1]. As described by several studies, levels of prenatal sex hormones can be related to the digit ratio of the index (2D) and ring (4D) finger [2]. It has been known that males tend to have longer fourth digits relative to second digits than females, indicating higher levels of fetal testosterone in comparison to estrogen in males [2]. As the development of the central nervous system (CNS) is also influenced by prenatal sex hormones, it has been suggested that the 2D:4D digit ratio may be a biomarker for the risk of developing CNS diseases such as autism. One study found that N = 72 children diagnosed with autism had lower 2D:4D digit ratios when compared to age-matched healthy controls [3], and a 2012 meta-analysis confirmed that adults with autism tend to have a lower 2D:4D digit ratio [4]. However, recent studies could not replicate these findings [5]. Aim(s) of the study: To determine the usefulness of the 2D:4D digit ratio as biomarker for autism spectrum disorder. Methods: Participants were recruited among students from Utrecht University. For both hands, digit lengths of the second (2D, index finger) and fourth (4D, ring finger) finger were measured
using digital Vernier calipers recording to 0.01 mm. In addition to demographics, the Autism Spectrum Quotient (AQ) questionnaire was completed. The AQ is divided into four subscales, each assessing a different aspect of ASD. The subscales comprise ‘social insights and behavior’, ‘difficulties with change’, ‘communication’, ‘phantasy and imagination’, and ‘detail orientation’. Using correlational analyses, the relationship between the 2D:4D digit ratio and the overall AQ scores and those of its subscales was computed. Results of participants with dove-type personality (2D:4D >1.00) were compared to those with a hawk-type personality (2D:4D <1.00). Analyses were also conducted for men and women separately. Results: N = 271 healthy volunteers with an average age of 29 years old participated in the study. 54.2% of the participants were women, 45.8% were men. Overall, no significant correlations were observed between the AQ total score and its subscales and the 2D:4D digit ratio. For women, also no significant correlations were found. For men, a significant correlation was found between the left 2D:4D digit ratio and the AQ subscale ‘difficulties with change’ (r = 0.189; p = 0.038). There was no significant difference between dove-type and hawk-type participants on any of the AQ subscales, nor with the total AQ score. Conclusions: In contrast to previous research, we did not find a significant association between the 2D:4D digit ratio and autism spectrum disorder scores. Although our data suggests that the 2D:4D digit ratio is not a suitable biomarker to identify individuals with an increased risk of having autism spectrum disorder, it should be taken into account that we investigated a nonclinical healthy student sample. Future studies should be conducted in patients that are formally diagnosed with autism. References [1] Davis, P.D., Pfaff, D., 2014. Sexually dimorphic responses to early adversity: implications for affective problems and autism spectrum disorder. Psychoneuroendocrinology. 49, 11−25. [2] Manning J., Kilduff L., Cook C., Crewther B., Fink B., 2014. Digit ratio (2D:4D): A biomarker for prenatal sex steroids and adult sex steroids in challenge situations. 30, 5−9. [3] Manning J.T., Baron-Cohen S., Wheelwright S., Sanders G., 2001. The 2nd and 4th digit ratio and autism. Dev Med Child Neurol. 43, 160−4. [4] H¨onekopp, J., 2012. Digit ratio 2D:4D in relation to autism spectrum disorders, empathizing, and systemizing: a quantitative review. Autism Res, 5, 221−30. [5] Guyatt, A.L., Heron, J., Knight, Ble C., Golding, J., Rai, D., 2015. Digit ratio and autism spectrum disorders in the Avon Longitudinal Study of Parents and Children: a birth cohort study. BMJ open. 5, e007433. Disclosure statement: This research was supported by Utrecht University. Joris Verster has received grants / research support from The Dutch Ministry of Infrastructure and the Environment, Janssen Research and Development, Nutricia, Takeda, Red Bull, and has acted as a consultant for Canadian Beverage Association, Centraal Bureau Drogisterijbedrijven, Coleman Frost, Danone, Deenox, Eisai, Janssen, Jazz, Purdue, Red Bull, Sanofi-Aventis, Sepracor, Takeda, Transcept, Trimbos Institute, and Vital Beverages. Johan Garssen is part-time employee of Nutricia.
P.7.b.020 Psychiatric disorders associated to incontinentia pigmenti: two case reports L. Espinosa1 ° , A. Fortea1 , I. Dom´ınguez1 , I. Molinero2 , A. Morer3 , I. Baeza3 , G. Sugranyes3 1 Hospital Clinic De Barcelona, Psychiatry, Barcelona, Spain; 2 Hospital Santa Maria, Psychiatry, Lleida, Spain; 3 Hospital Clinic De Barcelona, Child and Adolescent Psychiatry, Barcelona, Spain Introduction: Incontinentia pigmenti (IP) is a rare X-linked dominant syndrome (incidence 0.0025%) which manifests with skin, teeth, ocular and neurological abnormalities, that usually