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Abstracts of the 26Th World Congress of Psychiatric Genetics

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Abstracts of the 26Th World Congress of Psychiatric Genetics ARTICLE IN PRESS JID: NEUPSY [m6+; October 4, 2018;17:33 ] European Neuropsychopharmacology (2018) 000, 1–78 www.elsevier.com/locate/euroneuro Abstracts of the 26th World Congress of Psychiatric Genetics (WCPG): Poster Abstracts: Friday Friday, October 12, 2018 and an extensive clinical and sociodemographic characteri- zation. All evaluations were performed by psychiatrics blind to the previous diagnosis status. Subjects whose symptoms remitted in at least one wave were considered as remit- Poster Session I ters (n = 16) and those who fulfilled diagnostic criteria in all 11:30 a.m. - 1:30 p.m. waves were considered as persisters n = 66). Results: A significant difference between persisters and re- F1 mitters was observed in the left (P = 0.030; F = 4.916) and NEUROIMAGING GENETICS OF REMISSION AND PER- right (P = 0.029; F = 4.975) putamen, where remitters pre- SISTENCE IN ADULTHOOD ADHD sented smaller volumes. In a preliminary single gene ap- proach, we evaluated the variant SYT1-rs2251214, which Renata Basso Cupertino 1, Cibele Edom Bandeira 1, was associated with ADHD susceptibility and other external- Felipe Almeida Picon 1, Diana Müller 1, Bruna Santos da izing comorbidities in this sample, as well as treatment re- Silva 1, Djenifer B. Kappel 1, Maria Eduarda Tavares 1, sponse and persistence. This variant showed a trend towards Junior Pacer 1, Vitor Breda 2, Stefania Pigatto Teche 2, association with right pallidum volume (P = 0.060) and with Carlos A.I. Salgado 1, Eduardo S. Vitola 1, ADHD trajectory (persistence/remission) (P = 0.071). Eugenio H. Grevet 1, Claiton H.D. Bau 1 Discussion: As the ENIGMA mega-analysis pointed out, ADHD in older age is still a blind spot in neuroimaging research. 1 UFRGS Our preliminary findings suggest a role of the basal ganglia 2 Hospital de Clínicas de Porto Alegre on the ADHD trajectory. In this, an ongoing project, we aim to evaluate a larger sample size and include genome-wide Background: Several brain regions were shown to be al- approaches in order to obtain a more comprehensive view tered in children and adults with ADHD. The ENIGMA cross- of the genetic features underlying ADHD neurobiology. sectional mega-analysis has confirmed these alterations and provided a model of ADHD as a disorders of maturation de- Disclosure: Nothing to disclose. lay, based on more pronounced effects in childhood. The doi: 10.1016/j.euroneuro.2018.08.081 trajectory of ADHD symptomatology has been the focus of several debates questioning it as not simply a neurodevel- opmental disorder. Indeed, cohorts and longitudinal studies F2 have demonstrated both late-onset of symptoms and age- ELUCIDATING THE GENETIC AND BIOLOGICAL FAC- independent remission. Our aim is to evaluate the relation- TORS UNDERLYING THE RELATIONSHIP BETWEEN ADHD ship between symptoms remission and the brain alterations AND BMI VARIATION reported in the ENIGMA mega-analysis (accumbens, amyg- dala, caudate, hippocampus, putamen and intracranial vol- Nina Roth Mota 1, Marieke Klein 1, Geert Poelmans 1, ume) and how they are related with genetic variants previ- Noèlia Fernàndez-Castillo 2, Bàrbara Torrico 3, ously associated with ADHD. Tessel E. Galesloot 1, Lambertus ALM Kiemeney 1, Methods: This study assessed eighty-two subjects (mean Bru Cormand 2, Alejandro Arias-Vásquez 1, Barbara Franke 1 age currently 46 years old) that had been diagnosed with ADHD and later evaluated in a 7-year follow up (Karam et 1 Radboud University Medical Center, Nijmegen al, 2015), this third wave of evaluation includes the acqui- 2 University of Barcelona, Centro Nacional de Investi- sition of magnetic resonance imaging (MRI –3 Tesla) data gación Biomédica en Red de Enfermedades Raras (CIBERER), 0924-977X ARTICLE IN PRESS JID: NEUPSY [m6+; October 4, 2018;17:33 ] 2 Abstracts Instituto de Salud Carlos III, Institut de Biomedicina de la that neuroplasticity, a common feature of both neuronal Universitat de Barcelona (IBUB), Institut de Recerca Sant CREB signalling and NF-KB signalling, could play a key role Joan de Déu (IR-SJD), Esplugues de Llobregat in this relationship. Given the great impact both ADHD 3 Universitat de Barcelona and obesity have on society, it is important to further un- ravel the biological mechanisms that are disturbed in both Background: Attention-Deficit/Hyperactivity Disorder conditions. (ADHD) is frequently associated with other psychiatric and somatic conditions. One of the most important non- Disclosure: Nothing to disclose. psychiatric comorbidities of ADHD, in terms of public doi: 10.1016/j.euroneuro.2018.08.082 health, is obesity. Clinical overlap between ADHD and obesity is well documented, with studies showing an increased prevalence of obesity in ADHD patients and F3 higher rates of ADHD in obese individuals. The latest ADHD GLOBAL 5-METHYLCYTOSINE LEVELS IN ADULTS WITH GWAS meta-analysis showed significant genetic correlations ATTENTION DEFICIT/HYPERACTIVITY DISORDER between ADHD and all classes of obesity (rg = 0.29-0.34) and obesity-related traits, such as body-mass-index (BMI; Diana Müller 1, Natasha Assis-Figueira 2, = rg 0.26) (Demontis et al, BioRxiv 2017). However, the Renata Basso Cupertino 1, Bruna S. da Silva 1, biological mechanisms driving this association are largely Cibele Edom Bandeira 1, Djenifer B. Kappel 1, unknown. Some candidate systems have been suggested, Mariele F. Charão 3, Rafael Linden 3, Carlos A.I. Salgado 1, e.g., disturbances in the circadian rhythm (CIRCA) and Eugenio H. Grevet 4, Claiton H.D. Bau 1, Diego L. Rovaris 4 dopaminergic neurotransmission (DOPA) systems. Methods: We examined the association of ADHD polygenic 1 Universidade Federal do Rio Grande do Sul risk scores (PRS) with obesity risk and BMI variation in the 2 Unisinos general population, as well as the association of BMI-PRS 3 Universidade Feevale and ADHD-related measures. We used the results from the 4 Hospital de Clínicas de Porto Alegre latest ADHD GWAS (see above; N(Euro) = 19,099 cases and 34,194 controls) and BMI GWAS (N = 681,275; Yengo et al, Background: A very small fraction of the heritability in psy- BioRxiv 2018) as discovery samples. Our target sample was chiatric disorders is explained by molecular genetics find- a Dutch population cohort ascertained by the Nijmegen ings. In this sense, approaches able to catch environmental Biomedical Study (N = ∼3,200 adults). We also tested the as- effects might help to disentangle the biology of these dis- sociation of CIRCA and DOPA gene-sets with the ADHD and orders. Epigenetic studies, especially the methylation ones, BMI GWAS results mentioned above. Lastly, in order to iden- have emerged as an important way to summarize the inter- tify common biological mechanisms through a genome-wide actions between environmental and genetic factors. Most approach, we performed a gene-based cross-disorder meta- of the methylation studies published so far analyzed spe- analysis of these GWASs, followed by canonical pathway and cific genes or differential methylation in array-based meth- network enrichment analyses using Ingenuity. ods. Although a considerable fraction of the few studies fo- Results: ADHD-PRS were significantly associated with obe- cused on the overall analysis of global 5-methylcitosine (5- sity risk (R2 = 1.0%; P = 5.1E-4) and BMI variation (R2 = 0.66%; mC) levels showed significant differences between patients P = 2.4E-6). Regarding BMI-PRS, a significant association with (e.g. lower levels in Bipolar Disorder and MDD) and controls, the presence of ADHD symptoms during childhood was ob- there are no studies on ADHD. We aim to test the association served (R2 = 0.75%; P = 1.1E-4). When current inattention between global 5-mC levels and ADHD. (IA) and hyperactivity/impulsivity (HI) scores were anal- Methods: Our sample comprised 183 adults diagnosed with ysed separately, a significant association of BMI-PRS and ADHD (DSM-IV) and 149 non-ADHD volunteers. All subjects HI scores (R2 = 0.35%; P = 9.4E-4) was seen, suggesting that had European ancestry. DNA was extracted from whole this symptom domain has a more prominent role in the blood and aliquots of 2 micrograms were used for the ADHD-obesity(-BMI) relationship. Gene-set association anal- methylation treatment protocol. Treated samples were yses showed that the CIRCA gene-set was only associ- composed by DNA nucleotides (free of any RNA) which were ated with BMI, while the DOPA gene-set was associated submitted to separation in HPLC (280nm, 20 grades) accord- with both ADHD and BMI. In our genome-wide approach, ing to differential elution times. 5-mC levels were obtained a total of 206 genome-wide significant genes showed in- by the following ratio: 5-mC/(C + 5-mC)x100. creased significance compared to both original GWASs. En- Results: A significant difference in the mean global methy- richment analyses with these genes revealed one signifi- lation level (P < 0.001) was detected between patients with cant canonical pathway, namely “CREB Signalling in Neu- ADHD (3.630; SD = 0.454) and controls (3.957; SD = 0.482). rons” (PBH = 0.035), containing 9 genes. The top enriched Women had lower methylation levels than men (3.483 and network contained 28 genes and was centred around the 3.812, respectively; P < 0.001). NF-KB complex. Discussion: In conclusion, in terms of a shared biology un- derlying the relationship between ADHD and obesity (repre- sented by BMI), our results so far support the involvement of the dopaminergic neurotransmission system through a candidate gene-set approach. Furthermore, they indicate ARTICLE IN PRESS JID: NEUPSY [m6+; October 4, 2018;17:33 ] Abstracts 3 Discussion: Our findings point to a global 5-mC reduction in F5 subjects affected by ADHD, notably among women. These EPIGENETIC SIGNATURE FOR ATTENTION DEFICIT results are consistent with previous findings of sex differ- HYPERACTIVITY DISORDER: IDENTIFICATION OF MIR- ences in DNA methylation.
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