Genetics of attention-deficit/hyperactivity disorder: current findings and future directions

References

• American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV (4th Edition). American Psychiatric Publishing Inc., DC, USA, (1994).
   Google Scholar
• Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am. J. Psychiatry 164(6), 942–948 (2007).
   PubMed Web of Science ®Google Scholar
• Faraone SV, Biederman J, Mick E. The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies. Psychol. Med. 36(2), 159–165 (2006).
   PubMed Web of Science ®Google Scholar
• Barkley RA. Major life activity and health outcomes associated with attention-deficit/hyperactivity disorder. J. Clin. Psychiatry 63(Suppl. 12), 10–15 (2002).
   PubMed Web of Science ®Google Scholar
• Klein RG, Mannuzza S, Olazagasti MA et al. Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch. Gen. Psychiatry 69(12), 1295–1303 (2012).
   PubMed Web of Science ®Google Scholar
• Spencer TJ. ADHD and comorbidity in childhood. J. Clin. Psychiatry 67(Suppl. 8), 27–31 (2006).
   PubMed Web of Science ®Google Scholar
• Yoshimasu K, Barbaresi WJ, Colligan RC et al. Childhood ADHD is strongly associated with a broad range of psychiatric disorders during adolescence: a population-based birth cohort study. J. Child Psychol. Psychiatry. 53(10), 1036–1043 (2012).
   PubMed Web of Science ®Google Scholar
• Genro JP, Kieling C, Rohde LA, Hutz MH. Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses. Expert Rev. Neurother. 10(4), 587–601 (2010).
   PubMed Web of Science ®Google Scholar
• Thapar A, Cooper M, Eyre O, Langley K. What have we learnt about the causes of ADHD? J. Child Psychol. Psychiatry. 54(1), 3–16 (2013).
   PubMed Web of Science ®Google Scholar
• Faraone SV, Perlis RH, Doyle AE et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol. Psychiatry 57(11), 1313–1323 (2005).
   PubMed Web of Science ®Google Scholar
• Cortese S. The neurobiology and genetics of attention-deficit/hyperactivity disorder (ADHD): what every clinician should know. Eur. J. Paediatr. Neurol. 16(5), 422–433 (2012).
   PubMed Web of Science ®Google Scholar
• Tripp G, Wickens JR. Neurobiology of ADHD. Neuropharmacology 57(7–8), 579–589 (2009).
   PubMed Web of Science ®Google Scholar
• Kieling C, Goncalves RR, Tannock R, Castellanos FX. Neurobiology of attention deficit hyperactivity disorder. Child Adolesc. Psychiatr. Clin. N. Am. 17(2), 285–307, viii (2008).
   PubMed Web of Science ®Google Scholar
• Purper-Ouakil D, Ramoz N, Lepagnol-Bestel AM, Gorwood P, Simonneau M. Neurobiology of attention deficit/hyperactivity disorder. Pediatr. Res. 69(5 Pt 2), 69R–76R (2011).
   PubMedGoogle Scholar
• Giedd JN, Rapoport JL. Structural MRI of pediatric brain development: what have we learned and where are we going? Neuron 67(5), 728–734 (2010).
   PubMed Web of Science ®Google Scholar
• Durston S. A review of the biological bases of ADHD: what have we learned from imaging studies? Ment. Retard. Dev. Disabil. Res. Rev. 9(3), 184–195 (2003).
   PubMedGoogle Scholar
• Durston S, Mulder M, Casey BJ, Ziermans T, van Engeland H. Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder. Biol. Psychiatry 60(10), 1062–1070 (2006).
   PubMed Web of Science ®Google Scholar
• Wender PH, Epstein RS, Kopin IJ, Gordon EK. Urinary monoamine metabolites in children with minimal brain dysfunction. Am. J. Psychiatry 127(10), 1411–1415 (1971).
   PubMed Web of Science ®Google Scholar
• Yang B, Chan RC, Jing J, Li T, Sham P, Chen RY. A meta-analysis of association studies between the 10-repeat allele of a VNTR polymorphism in the 3´-UTR of dopamine transporter gene and attention deficit hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 144B(4), 541–550 (2007).
   PubMed Web of Science ®Google Scholar
• Li D, Sham PC, Owen MJ, He L. Meta-analysis shows significant association between dopamine system genes and attention deficit hyperactivity disorder (ADHD). Hum. Mol. Genet. 15(14), 2276–2284 (2006).
   PubMed Web of Science ®Google Scholar
• Purper-Ouakil D, Wohl M, Mouren MC, Verpillat P, Adès J, Gorwood P. Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder. Psychiatr. Genet. 15(1), 53–59 (2005).
   PubMed Web of Science ®Google Scholar
• Gizer IR, Ficks C, Waldman ID. Candidate gene studies of ADHD: a meta-analytic review. Hum. Genet. 126(1), 51–90 (2009).
   PubMed Web of Science ®Google Scholar
• Brookes KJ, Mill J, Guindalini C et al. A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Arch. Gen. Psychiatry 63(1), 74–81 (2006).
   PubMed Web of Science ®Google Scholar
• Brookes K, Xu X, Chen W et al. The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes. Mol. Psychiatry 11(10), 934–953 (2006).
   PubMed Web of Science ®Google Scholar
• Asherson P, Brookes K, Franke B et al. Confirmation that a specific haplotype of the dopamine transporter gene is associated with combined-type ADHD. Am. J. Psychiatry 164(4), 674–677 (2007).
   PubMed Web of Science ®Google Scholar
• Genro JP, Polanczyk GV, Zeni C et al. A common haplotype at the dopamine transporter gene 5′ region is associated with attention-deficit/hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(8), 1568–1575 (2008).
   PubMedGoogle Scholar
• Zhou K, Chen W, Buitelaar J et al. Genetic heterogeneity in ADHD: DAT1 gene only affects probands without CD. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(8), 1481–1487 (2008).
   PubMedGoogle Scholar
• Franke B, Vasquez AA, Johansson S et al. Multicenter analysis of the SLC6A3/DAT1 VNTR haplotype in persistent ADHD suggests differential involvement of the gene in childhood and persistent ADHD. Neuropsychopharmacology 35(3), 656–664 (2010).
   PubMed Web of Science ®Google Scholar
• Bidwell LC, Willcutt EG, McQueen MB et al. A family based association study of DRD4, DAT1, and 5HTT and continuous traits of attention-deficit hyperactivity disorder. Behav. Genet. 41(1), 165–174 (2011).
   PubMed Web of Science ®Google Scholar
• Benjamin J, Li L, Patterson C, Greenberg BD, Murphy DL, Hamer DH. Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking. Nat. Genet. 12(1), 81–84 (1996).
   PubMed Web of Science ®Google Scholar
• Ebstein RP, Novick O, Umansky R et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat. Genet. 12(1), 78–80 (1996).
   PubMed Web of Science ®Google Scholar
• Chang FM, Kidd JR, Livak KJ, Pakstis AJ, Kidd KK. The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus. Hum. Genet. 98(1), 91–101 (1996).
   PubMed Web of Science ®Google Scholar
• Grady DL, Chi HC, Ding YC et al. High prevalence of rare dopamine receptor D4 alleles in children diagnosed with attention-deficit hyperactivity disorder. Mol. Psychiatry 8(5), 536–545 (2003).
   PubMed Web of Science ®Google Scholar
• Tovo-Rodrigues L, Rohde LA, Roman T et al. Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD? Searching for an effect of allelic heterogeneity. Mol. Psychiatry 17(5), 520–526 (2012).
   PubMed Web of Science ®Google Scholar
• Grady DL, Harxhi A, Smith M et al. Sequence variants of the DRD4 gene in autism: further evidence that rare DRD4 7R haplotypes are ADHD specific. Am. J. Med. Genet. B Neuropsychiatr. Genet. 136B(1), 33–35 (2005).
   PubMedGoogle Scholar
• Sánchez-Mora C, Ribasés M, Casas M et al. Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: a meta-analysis in four European populations. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B(5), 600–612 (2011).
   PubMed Web of Science ®Google Scholar
• Smith TF. Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD: stronger association with AD/HD combined type. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B(6), 1189–1199 (2010).
   PubMed Web of Science ®Google Scholar
• Cichon S, Craddock N, Daly M et al. Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am. J. Psychiatr. 166(5), 540–556 (2009).
   PubMed Web of Science ®Google Scholar
• Lesch KP, Timmesfeld N, Renner TJ et al. Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies. J. Neural Transm. 115(11), 1573–1585 (2008).
   PubMed Web of Science ®Google Scholar
• Neale BM, Lasky-Su J, Anney R et al. Genome-wide association scan of attention deficit hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(8), 1337–1344 (2008).
   PubMed Web of Science ®Google Scholar
• Mick E, Todorov A, Smalley S et al. Family-based genome-wide association scan of attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 49(9), 898–905.e3 (2010).
   PubMed Web of Science ®Google Scholar
• Neale BM, Medland S, Ripke S et al.; IMAGE II Consortium Group. Case–control genome-wide association study of attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 49(9), 906–920 (2010).
   PubMed Web of Science ®Google Scholar
• Hinney A, Scherag A, Jarick I et al.; Psychiatric GWAS Consortium: ADHD subgroup. Genome-wide association study in German patients with attention deficit/hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B(8), 888–897 (2011).
   PubMed Web of Science ®Google Scholar
• Stergiakouli E, Hamshere M, Holmans P et al.; deCODE Genetics; Psychiatric GWAS Consortium. Investigating the contribution of common genetic variants to the risk and pathogenesis of ADHD. Am. J. Psychiatry 169(2), 186–194 (2012).
   PubMed Web of Science ®Google Scholar
• Lasky-Su J, Neale BM, Franke B et al. Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(8), 1345–1354 (2008).
   PubMed Web of Science ®Google Scholar
• Franke B, Neale BM, Faraone SV. Genome-wide association studies in ADHD. Hum. Genet. 126(1), 13–50 (2009).
   PubMed Web of Science ®Google Scholar
• Rivero O, Sich S, Popp S, Schmitt A, Franke B, Lesch KP. Impact of the ADHD-susceptibility gene CDH13 on development and function of brain networks. Eur. Neuropsychopharmacol. 242, 135–141 (2012).
   Google Scholar
• Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160(4), 636–645 (2003).
   PubMed Web of Science ®Google Scholar
• Kendler KS, Neale MC. Endophenotype: a conceptual analysis. Mol. Psychiatry 15(8), 789–797 (2010).
   PubMed Web of Science ®Google Scholar
• Arias-Vásquez A, Altink ME, Rommelse NN et al. CDH13 is associated with working memory performance in attention deficit/hyperactivity disorder. Genes Brain Behav. 10(8), 844–851 (2011).
   PubMed Web of Science ®Google Scholar
• de Silva MG, Elliott K, Dahl HH et al. Disruption of a novel member of a sodium/hydrogen exchanger family and DOCK3 is associated with an attention deficit hyperactivity disorder-like phenotype. J. Med. Genet. 40(10), 733–740 (2003).
   PubMed Web of Science ®Google Scholar
• Markunas CA, Quinn KS, Collins AL et al. Genetic variants in SLC9A9 are associated with measures of attention-deficit/hyperactivity disorder symptoms in families. Psychiatr. Genet. 20(2), 73–81 (2010).
   PubMedGoogle Scholar
• Zhang-James Y, DasBanerjee T, Sagvolden T, Middleton FA, Faraone SV. SLC9A9 mutations, gene expression, and protein–protein interactions in rat models of attention-deficit/hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B(7), 835–843 (2011).
   PubMedGoogle Scholar
• Neale BM, Medland SE, Ripke S et al.; Psychiatric GWAS Consortium: ADHD Subgroup. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 49(9), 884–897 (2010).
   PubMed Web of Science ®Google Scholar
• Poelmans G, Pauls DL, Buitelaar JK, Franke B. Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder. Am. J. Psychiatry 168(4), 365–377 (2011).
   PubMed Web of Science ®Google Scholar
• Mukherjee S, Manahan-Vaughan D. Role of metabotropic glutamate receptors in persistent forms of hippocampal plasticity and learning. Neuropharmacology 66, 65–81 (2013).
   PubMed Web of Science ®Google Scholar
• Elia J, Gai X, Xie HM et al. Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes. Mol. Psychiatry 15(6), 637–646 (2010).
   PubMed Web of Science ®Google Scholar
• Elia J, Glessner JT, Wang K et al. Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder. Nat. Genet. 44(1), 78–84 (2012).
   PubMed Web of Science ®Google Scholar
• Williams NM, Zaharieva I, Martin A et al. Rare chromosomal deletions and duplications in attention-deficit hyperactivity disorder: a genome-wide analysis. Lancet 376(9750), 1401–1408 (2010).
   PubMed Web of Science ®Google Scholar
• Langley K, Martin J, Agha SS et al. Clinical and cognitive characteristics of children with attention-deficit hyperactivity disorder, with and without copy number variants. Br. J. Psychiatry 199(5), 398–403 (2011).
   PubMedGoogle Scholar
• Ramalingam A, Zhou XG, Fiedler SD et al. 16p13.11 duplication is a risk factor for a wide spectrum of neuropsychiatric disorders. J. Hum. Genet. 56(7), 541–544 (2011).
   PubMed Web of Science ®Google Scholar
• Lionel AC, Crosbie J, Barbosa N et al. Rare copy number variation discovery and cross-disorder comparisons identify risk genes for ADHD. Sci. Transl. Med. 3(95), 95ra75 (2011).
   PubMed Web of Science ®Google Scholar
• Williams NM, Franke B, Mick E et al. Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. Am. J. Psychiatry 169(2), 195–204 (2012).
   PubMed Web of Science ®Google Scholar
• Lesch KP, Selch S, Renner TJ et al. Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Mol. Psychiatry 16(5), 491–503 (2011).
   PubMed Web of Science ®Google Scholar
• Jarick I, Volckmar AL, Pütter C et al. Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder. Mol. Psychiatry doi:10.1038/mp.2012.161 (2012) (Epub ahead of print).
   PubMedGoogle Scholar
• Arcos-Burgos M, Jain M, Acosta MT et al. A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to ADHD and predicts effectiveness of stimulant medication. Mol. Psychiatry 15(11), 1053–1066 (2010).
   PubMed Web of Science ®Google Scholar
• Ribasés M, Ramos-Quiroga JA, Sánchez-Mora C et al. Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study. Genes Brain Behav. 10(2), 149–157 (2011).
   PubMed Web of Science ®Google Scholar
• Acosta MT, Vélez JI, Bustamante ML, Balog JZ, Arcos-Burgos M, Muenke M. A two-locus genetic interaction between LPHN3 and 11q predicts ADHD severity and long-term outcome. Transl. Psychiatry 1, e17 (2011).
   Google Scholar
• Jain M, Vélez JI, Acosta MT et al. A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD. Mol. Psychiatry 17(7), 741–747 (2012).
   PubMed Web of Science ®Google Scholar
• Martinez AF, Muenke M, Arcos-Burgos M. From the black widow spider to human behavior: latrophilins, a relatively unknown class of G protein-coupled receptors, are implicated in psychiatric disorders. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B(1), 1–10 (2011).
   PubMedGoogle Scholar
• Lange M, Norton W, Coolen M et al. The ADHD-susceptibility gene lphn3.1 modulates dopaminergic neuron formation and locomotor activity during zebrafish development. Mol. Psychiatry 17(9), 946–954 (2012).
   PubMed Web of Science ®Google Scholar
• Wallis D, Hill DS, Mendez IA et al. Initial characterization of mice null for Lphn3, a gene implicated in ADHD and addiction. Brain Res. 1463, 85–92 (2012).
   PubMed Web of Science ®Google Scholar
• Brookes KJ, Hawi Z, Kirley A, Barry E, Gill M, Kent L. Association of the steroid sulfatase (STS) gene with attention deficit hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(8), 1531–1535 (2008).
   PubMed Web of Science ®Google Scholar
• Brookes KJ, Hawi Z, Park J, Scott S, Gill M, Kent L. Polymorphisms of the steroid sulfatase (STS) gene are associated with attention deficit hyperactivity disorder and influence brain tissue mRNA expression. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B(8), 1417–1424 (2010).
   PubMed Web of Science ®Google Scholar
• Stergiakouli E, Langley K, Williams H et al. Steroid sulfatase is a potential modifier of cognition in attention deficit hyperactivity disorder. Genes Brain Behav. 10(3), 334–344 (2011).
   PubMed Web of Science ®Google Scholar
• Wang LJ, Huang YS, Hsiao CC et al. Salivary dehydroepiandrosterone, but not cortisol, is associated with attention deficit hyperactivity disorder. World J. Biol. Psychiatry 12(2), 99–109 (2011).
   PubMed Web of Science ®Google Scholar
• Davies W, Humby T, Kong W, Otter T, Burgoyne PS, Wilkinson LS. Converging pharmacological and genetic evidence indicates a role for steroid sulfatase in attention. Biol. Psychiatry 66(4), 360–367 (2009).
   PubMed Web of Science ®Google Scholar
• Manolio TA, Collins FS, Cox NJ et al. Finding the missing heritability of complex diseases. Nature 461(7265), 747–753 (2009).
   PubMed Web of Science ®Google Scholar
• Visscher PM, Goddard ME, Derks EM, Wray NR. Evidence-based psychiatric genetics, AKA the false dichotomy between common and rare variant hypotheses. Mol. Psychiatry 17(5), 474–485 (2012).
   PubMed Web of Science ®Google Scholar
• Zuk O, Hechter E, Sunyaev SR, Lander ES. The mystery of missing heritability: Genetic interactions create phantom heritability. Proc. Natl Acad. Sci. USA 109(4), 1193–1198 (2012).
   PubMed Web of Science ®Google Scholar
• van der Sluis S, Verhage M, Posthuma D, Dolan CV. Phenotypic complexity, measurement bias, and poor phenotypic resolution contribute to the missing heritability problem in genetic association studies. PLoS ONE 5(11), e13929 (2010).
   Google Scholar
• Willcutt EG, Nigg JT, Pennington BF et al. Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes. J. Abnorm. Psychol. 121(4), 991–1010 (2012).
   PubMed Web of Science ®Google Scholar
• Purcell SM, Wray NR, Stone JL et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460(7256), 748–752 (2009).
   PubMed Web of Science ®Google Scholar
• Derks EM, Vorstman JA, Ripke S, Kahn RS, Ophoff RA; Schizophrenia Psychiatric Genomic Consortium. Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis. PLoS ONE 7(6), e37852 (2012).
   Google Scholar
• Lesch KP, Merker S, Reif A, Novak M. Dances with black widow spiders: dysregulation of glutamate signalling enters centre stage in ADHD. Eur. Neuropsychopharmacol. 64(4), 279–287 (2012).
   Google Scholar
• Sagvolden T, Johansen EB, Wøien G et al. The spontaneously hypertensive rat model of ADHD – the importance of selecting the appropriate reference strain. Neuropharmacology 57(7–8), 619–626 (2009).
   PubMedGoogle Scholar
• Gainetdinov RR, Mohn AR, Bohn LM, Caron MG. Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. Proc. Natl Acad. Sci. USA 98(20), 11047–11054 (2001).
   PubMed Web of Science ®Google Scholar
• Mick E, Neale B, Middleton FA, McGough JJ, Faraone SV. Genome-wide association study of response to methylphenidate in 187 children with attention-deficit/hyperactivity disorder. Am. J. Med. Genet. B Neuropsychiatr. Genet. 147B(8), 1412–1418 (2008).
   PubMed Web of Science ®Google Scholar
• Chang S, Zhang W, Gao L, Wang J. Prioritization of candidate genes for attention deficit hyperactivity disorder by computational analysis of multiple data sources. Protein Cell 3(7), 526–534 (2012).
   PubMedGoogle Scholar
• Nigg J, Nikolas M, Burt SA. Measured gene-by-environment interaction in relation to attention-deficit/hyperactivity disorder. J. Am. Acad. Child Adolesc. Psychiatry 49(9), 863–873 (2010).
   PubMed Web of Science ®Google Scholar
• Helms CM, Gubner NR, Wilhelm CJ, Mitchell SH, Grandy DK. D4 receptor deficiency in mice has limited effects on impulsivity and novelty seeking. Pharmacol. Biochem. Behav. 90(3), 387–393 (2008).
   PubMedGoogle Scholar
• Holmes A, Hollon TR, Gleason TC et al. Behavioral characterization of dopamine D5 receptor null mutant mice. Behav. Neurosci. 115(5), 1129–1144 (2001).
   PubMed Web of Science ®Google Scholar
• Guilloux JP, David DJ, Xia L et al. Characterization of 5-HT(1A/1B)-/- mice: an animal model sensitive to anxiolytic treatments. Neuropharmacology 61(3), 478–488 (2011).
   PubMedGoogle Scholar
• Zhuang X, Gross C, Santarelli L, Compan V, Trillat AC, Hen R. Altered emotional states in knockout mice lacking 5-HT1A or 5-HT1B receptors. Neuropsychopharmacology 21(2 Suppl.), 52S–60S (1999).
   PubMed Web of Science ®Google Scholar