Browsing by Author "Faraone, Stephen V."

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Low cardiorespiratory fitness and obesity for ADHD in childhood and adolescence: A 6‐year cohort study
(2020-12-20) Muntaner Mas, Adrià; Ortega, Francisco B.; Femia, Pedro; Kiive, Evelyn; Evelyn, Diva; Mäestu, Jarek; Franke, Barbara; Reif, Andreas; Faraone, Stephen V.; Harro, Jaanus
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent disorder in childhood and identifying risk factors associated with developing ADHD during childhood and adolescence is relevant from a clinical and epidemiological point of view. This work examines (1) whether overweight/obesity and low cardiorespiratory fitness (CRF) are associated with increased ADHD symptoms in childhood (cross sectional analysis), and (2) whether overweight/obesity and low CRF levels during childhood predict increased ADHD symptoms in adolescence (longitudinal analysis). Data were examined from a longitudinal study of Estonian inhabitants who took part in the European Youth Heart Study (EYHS) in 1998 and 1999 (baseline age 9 years), who were re-evaluated 6 years later as part of the longitudinal Estonian Children Personality Behaviour and Health Study (ECPBHS). CRF was determined via an incremental maximal cycle-ergometer test, overweight/obesity was based on body mass index (BMI), and the 7-point af Klinteberg Hyperactivity Scale was used to assess ADHD symptoms at both time points. In the cross-sectional analysis, children with overweight/obesity were at greater risk of ADHD symptoms compared to underweight/normal-weight children, as were those unfit compared to fit children (OR=1.92 and 95%CI=1.02–3.55, and OR=1.84 and 95%CI=1.13–2.98, respectively). The cross-sectional association between BMI and ADHD symptoms was mediated by CRF (z=2.116, 42.9%; p=0.034). The longitudinal analysis showed being unfit in childhood was associated with a greater risk of increased ADHD symptoms 6 years later in adolescence (OR=2.26 and 95%CI=1.14–4.47), even after adjusting for baseline ADHD symptoms and BMI. Our result suggests that being unfit is an additional risk factor for increased ADHD symptoms during childhood and adolescence. The association between BMI and ADHD symptoms was mediated by CRF in the cross-sectional analysis and no association was seen between overweight/obesity and increased ADHD symptoms.
RBFOX1, encoding a splicing regulator, is a candidate gene for aggressive behavior
(Eur Neuropsychopharmacol., 2020) Fernàndez-Castillo, Noèlia; Gan, Gabriela; M.J. van Donkelaar, Marjolein; Vaht, Mariliis; Weber, Heike; Retz, Wolfgang; Meyer-Lindenberg, Andreas; Franke, Barbara; Harro, Jaanus; Reif, Andreas; Faraone, Stephen V.; Cormand, Bru
The RBFOX1 gene (or A2BP1) encodes a splicing factor important for neuronal development that has been related to autism spectrum disorder and other neurodevelopmental phenotypes. Evidence from complementary sources suggests that this gene contributes to aggressive behavior. Suggestive associations with RBFOX1 have been identified in genome-wide association studies (GWAS) of anger, conduct disorder, and aggressive behavior. Nominal association signals in RBFOX1 were also found in an epigenome-wide association study (EWAS) of aggressive behavior. Also, variants in this gene affect temporal lobe volume, a brain area that is altered in several aggression-related phenotypes. In animals, this gene has been shown to modulate aggressive behavior in Drosophila. RBFOX1 has also been associated with canine aggression and is upregulated in mice that show increased aggression after frustration of an expected reward. Associated common genetic variants as well as rare duplications and deletions affecting RBFOX1 have been identified in several psychiatric and neurodevelopmental disorders that are often comorbid with aggressive behaviors. In this paper, we comprehensively review the cumulative evidence linking RBFOX1 to aggression behavior and provide new results implicating RBFOX1 in this phenotype. Most of these studies (genetic and epigenetic analyses in humans, neuroimaging genetics, gene expression and animal models) are hypothesis-free, which strengthens the validity of the findings, although all the evidence is nominal and should therefore be taken with caution. Further studies are required to clarify in detail the role of this gene in this complex phenotype.
Variants of the aggression-related RBFOX1 gene in a population representative birth cohort study: aggressiveness, personality and alcohol use disorder
(2020) Vaht, Mariliis; Laas, Kariina; Fernàndez-Castillo, Noèlia; Kurrikoff, Triin; Kanarik, Margus; Faraone, Stephen V.; Tooding, Liina-Mai; Veidebaum, Toomas; Franke, Barbara; Reif, Andreas; Cormand, Bru; Harro, Jaanus
Background Recently RBFOX1, a gene encoding an RNA binding protein, has consistently been associated with aggressive and antisocial behaviour. Several loci in the gene have been nominally associated with aggression in genome-wide association studies; the risk alleles being more frequent in general population. We have hence examined the association of four RBFOX1 single nucleotide polymorphisms, previously found related to aggressive traits, with aggressiveness, personality, and alcohol use disorder in birth cohort representative samples. Methods We used both birth cohorts of the Estonian Children Personality Behaviour and Health Study (ECPBHS; original n=1,238). Aggressiveness was assessed using the Buss-Perry Aggression Questionnaire and the Lifetime History of Aggressiveness structured interview at age 25 (younger cohort) or 33 (older cohort). Big Five personality at age 25 was measured with self reports and the lifetime occurrence of alcohol use disorder assessed with the MINI interview. RBFOX1 polymorphisms rs809682, rs8062784, rs12921846 and rs6500744 were genotyped in all participants. Given the restricted size of the sample, correction for multiple comparisons was not applied. Results Aggressiveness was not significantly associated with RBFOX1 genotype. RBFOX1 rs8062784 was associated with neuroticism and rs809682 with extraversion. Two out of four analyzed RBFOX1 variants, rs8062784, and rs12921846, were associated with occurrence of alcohol use disorder. Conclusions In the birth cohort representative sample of the ECPBHS, no association of RBFOX1 with aggressiveness was found, but RBFOX1 variants affected basic personality traits and the prevalence of alcohol use disorder. Future studies on RBFOX1 should consider the moderating role of personality and alcohol use patterns in aggressiveness.