Genetics of Pediatric Anxiety Disorders

Child and Adolescent Psychiatric Clinics of North America

Volumn 21, Issue 3, 2012, Pages 479-500

  Sakolsky, Dara J ^a   McCracken, James T ^b   Nurmi, Erika L ^b  

^a UNIVERSITY OF PITTSBURGH   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Candidate genes; Genetics; Obsessive compulsive disorder; Panic disorder; Pediatric anxiety; Posttraumatic stress disorder

Indexed keywords

MONOAMINE; NEUROTRANSMITTER;

ANXIETY DISORDER; CNTNAP2 GENE; COMT GENE; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE TRANSMISSION; ENVIRONMENTAL FACTOR; EPIGENETICS; FAMILIAL DISEASE; FUNCTIONAL ASSESSMENT; GENE; GENERALIZED ANXIETY DISORDER; GENETIC ASSOCIATION; GENETIC DISORDER; GENETIC LINKAGE; GENETIC RISK; GENETIC SUSCEPTIBILITY; GENOMICS; GENOTYPE; GENOTYPE ENVIRONMENT INTERACTION; HEREDITY; HERITABILITY; HUMAN; HUMAN GENOME; INHERITANCE; LIFE EVENT; MENTAL DISEASE; MOLECULAR GENETICS; NEUROENDOCRINE SYSTEM; NEUROPEPTIDE S RECEPTOR GENE; NTRK2 GENE; OBSESSIVE COMPULSIVE DISORDER; ONSET AGE; PANIC; PATHOPHYSIOLOGY; PEDIATRIC ANXIETY DISORDER; PHENOTYPE; PHOBIA; POPULATION GENETICS; POSTTRAUMATIC STRESS DISORDER; PREVALENCE; PRIORITY JOURNAL; PSYCHOPHYSIOLOGY; REVIEW; SEPARATION ANXIETY; SEROTONIN TRANSPORTER GENE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SOCIAL PHOBIA; TMEM132D GENE;

ANXIETY DISORDERS; BIOMEDICAL RESEARCH; CHILD; EPIGENOMICS; GENES; GENETIC LINKAGE; GENOME, HUMAN; GENOTYPE; HUMANS; MEMBRANE PROTEINS; NERVE TISSUE PROTEINS; PEDIGREE; RECEPTOR, TRKB; RISK FACTORS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SIGNAL TRANSDUCTION;

EID: 84863877346     PISSN: 10564993     EISSN: 15580490     Source Type: Journal    
DOI: 10.1016/j.chc.2012.05.010     Document Type: Review

References (147)

1. Costello E.J., Egger H.L., Angold A. The developmental epidemiology of anxiety disorders: phenomenology, prevalence, and comorbidity. Child Adolesc Psychiatr Clin N Am 2005, 14(4):631-648. vii.
2. Pine D.S., Cohen P., Gurley D., et al. The risk for early-adulthood anxiety and depressive disorders in adolescents with anxiety and depressive disorders. Arch Gen Psychiatry 1998, 55(1):56-64.
3. Smoller J.W., Block S.R., Young M.M. Genetics of anxiety disorders: the complex road from DSM to DNA. Depress Anxiety 2009, 26(11):965-975.
4. Hettema J.M., Neale M.C., Kendler K.S. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001, 158(10):1568-1578.
5. van Grootheest D.S., Cath D.C., Beekman A.T., et al. Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet 2005, 8(5):450-458.
6. Walitza S., Wendland J.R., Gruenblatt E., et al. Genetics of early-onset obsessive-compulsive disorder. Eur Child Adolesc Psychiatry 2010, 19(3):227-235.
7. Weissman M.M., Bland R.C., Canino G.J., et al. The cross national epidemiology of obsessive compulsive disorder. The Cross National Collaborative Group. J Clin Psychiatry 1994, 55(Suppl):5-10.
8. Kessler R.C., Berglund P., Demler O., et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005, 62(6):593-602.
9. Stewart S.E., Geller D.A., Jenike M., et al. Long-term outcome of pediatric obsessive-compulsive disorder: a meta-analysis and qualitative review of the literature. Acta Psychiatr Scand 2004, 110(1):4-13.
10. Piacentini J., Bergman R.L., Keller M., et al. Functional impairment in children and adolescents with obsessive-compulsive disorder. J Child Adolesc Psychopharmacol 2003, 13(Suppl 1):S61-S69.
11. Saxena S., Rauch S.L. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am 2000, 23(3):563-586.
12. Kalra S.K., Swedo S.E. Children with obsessive-compulsive disorder: are they just "little adults"?. J Clin Invest 2009, 119(4):737-746.
13. Bolton D., Rijsdijk F., O'Connor T.G., et al. Obsessive-compulsive disorder, tics and anxiety in 6-year-old twins. Psychol Med 2007, 37(1):39-48.
14. Tambs K., Czajkowsky N., Roysamb E., et al. Structure of genetic and environmental risk factors for dimensional representations of DSM-IV anxiety disorders. Br J Psychiatry 2009, 195(4):301-307.
15. Pauls D.L. The genetics of obsessive-compulsive disorder: a review. Dialog Clin Neurosci 2010, 12(2):149-163.
16. Pinto A., Greenberg B.D., Grados M.A., et al. Further development of YBOCS dimensions in the OCD Collaborative Genetics study: symptoms vs. categories. Psychiatry Res 2008, 160(1):83-93.
17. Grabe H.J., Ruhrmann S., Ettelt S., et al. Familiality of obsessive-compulsive disorder in nonclinical and clinical subjects. Am J Psychiatry 2006, 163(11):1986-1992.
18. Hasler G., Pinto A., Greenberg B.D., et al. Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study. Biol Psychiatry 2007, 61(5):617-625.
19. Bienvenu O.J., Samuels J.F., Riddle M.A., et al. The relationship of obsessive-compulsive disorder to possible spectrum disorders: results from a family study. Biol Psychiatry 2000, 48(4):287-293.
20. Grados M.A., Riddle M.A., Samuels J.F., et al. The familial phenotype of obsessive-compulsive disorder in relation to tic disorders: the Hopkins OCD family study. Biol Psychiatry 2001, 50(8):559-565.
21. Black D.W., Noyes R., Goldstein R.B., et al. A family study of obsessive-compulsive disorder. Arch Gen Psychiatry 1992, 49(5):362-368.
22. Nestadt G., Di C.Z., Riddle M.A., et al. Obsessive-compulsive disorder: subclassification based on co-morbidity. Psychol Med 2009, 39(9):1491-1501.
23. Alsobrook I.J., Leckman J.F., Goodman W.K., et al. Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores. Am J Med Genet 1999, 88(6):669-675.
24. Cavallini M.C., Bertelli S., Chiapparino D., et al. Complex segregation analysis of obsessive-compulsive disorder in 141 families of eating disorder probands, with and without obsessive-compulsive disorder. Am J Med Genet 2000, 96(3):384-391.
25. Nestadt G., Lan T., Samuels J., et al. Complex segregation analysis provides compelling evidence for a major gene underlying obsessive-compulsive disorder and for heterogeneity by sex. Am J Hum Genet 2000, 67(6):1611-1616.
26. Shugart Y.Y., Samuels J., Willour V.L., et al. Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. Mol Psychiatry 2006, 11(8):763-770.
27. Hanna G.L., Veenstra-VanderWeele J., Cox N.J., et al. Genome-wide linkage analysis of families with obsessive-compulsive disorder ascertained through pediatric probands. Am J Med Genet 2002, 114(5):541-552.
28. Hanna G.L., Veenstra-Vanderweele J., Cox N.J., et al. Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder. Biol Psychiatry 2007, 62(8):856-862.
29. Ross J., Badner J., Garrido H., et al. Genomewide linkage analysis in Costa Rican families implicates chromosome 15q14 as a candidate region for OCD. Hum Genet 2011, 130(6):795-805.
30. Nestadt G., Wang Y., Grados M.A., et al. Homeobox genes in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2012, 159B(1):53-60.
31. Samuels J., Shugart Y.Y., Grados M.A., et al. Significant linkage to compulsive hoarding on chromosome 14 in families with obsessive-compulsive disorder: results from the OCD Collaborative Genetics Study. Am J Psychiatry 2007, 164(3):493-499.
32. Wang Y., Samuels J.F., Chang Y.C., et al. Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families. Am J Med Genet B Neuropsychiatr Genet 2009, 150B(1):33-40.
33. Willour V.L., Yao Shugart Y., Samuels J., et al. Replication study supports evidence for linkage to 9p24 in obsessive-compulsive disorder. Am J Hum Genet 2004, 75(3):508-513.
34. Mathews C., Badner J., Andresen J., et al. Genomewide linkage analysis of obsessive compulsive disorder implicates chromosome 1p36. Biol Psychiatry 2012, [Epub ahead of print].
35. Chakrabarty K., Bhattacharyya S., Christopher R., et al. Glutamatergic dysfunction in OCD. Neuropsychopharmacology 2005, 30(9):1735-1740.
36. MacMaster F.P., O'Neill J., Rosenberg D.R. Brain imaging in pediatric obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 2008, 47(11):1262-1272.
37. Maina G., Rosso G., Zanardini R., et al. Serum levels of brain-derived neurotrophic factor in drug-naive obsessive-compulsive patients: a case-control study. J Affect Disord 2010, 122(1-2):174-178.
38. O'Neill J., Piacentini J.C., Chang S., et al. MRSI correlates of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2012, 36(1):161-168.
39. Wu K., Hanna G.L., Rosenberg D.R., Arnold P.D. The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder. Pharmacol Biochem Behav 2012, 100(4):726-735.
40. Ting J.T., Feng G. Neurobiology of obsessive-compulsive disorder: insights into neural circuitry dysfunction through mouse genetics. Curr Opin Neurobiol 2011, 21(6):842-848.
41. Arnold P.D., Rosenberg D.R., Mundo E., Tharmalingam S., Kennedy J.L., Richter M.A. Association of a glutamate (NMDA) subunit receptor gene (GRIN2B) with obsessive-compulsive disorder: a preliminary study. Psychopharmacology (Berl) 2004, 174(4):530-538.
42. Arnold P.D., Macmaster F.P., Richter M.A., et al. Glutamate receptor gene (GRIN2B) associated with reduced anterior cingulate glutamatergic concentration in pediatric obsessive-compulsive disorder. Psychiatry Res 2009, 172(2):136-139.
43. Arnold P.D., Macmaster F.P., Hanna G.L., et al. Glutamate system genes associated with ventral prefrontal and thalamic volume in pediatric obsessive-compulsive disorder. Brain Imaging Behav 2009, 3(1):64-76.
44. Delorme R., Krebs M.O., Chabane N., et al. Frequency and transmission of glutamate receptors GRIK2 and GRIK3 polymorphisms in patients with obsessive compulsive disorder. NeuroReport 2004, 15(4):699-702.
45. Sampaio A.S., Fagerness J., Crane J., et al. Association between polymorphisms in GRIK2 gene and obsessive-compulsive disorder: a family-based study. CNS Neurosci Ther 2011, 17(3):141-147.
46. Bienvenu O.J., Wang Y., Shugart Y.Y., et al. Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet 2009, 150B(5):710-720.
47. Samuels J., Wang Y., Riddle M.A., et al. Comprehensive family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2011, 156B(4):472-477.
48. Wendland J.R., Moya P.R., Timpano K.R., et al. A haplotype containing quantitative trait loci for SLC1A1 gene expression and its association with obsessive-compulsive disorder. Arch Gen Psychiatry 2009, 66(4):408-416.
49. Shugart Y.Y., Wang Y., Samuels J.F., et al. A family-based association study of the glutamate transporter gene SLC1A1 in obsessive-compulsive disorder in 378 families. Am J Med Genet B Neuropsychiatr Genet 2009, 150B(6):886-892.
50. Stewart S.E., Fagerness J.A., Platko J., et al. Association of the SLC1A1 glutamate transporter gene and obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2007, 144B(8):1027-1033.
51. Dickel D.E., Veenstra-VanderWeele J., Cox N.J., et al. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry 2006, 63(7):778-785.
52. Arnold P.D., Sicard T., Burroughs E., et al. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry 2006, 63(7):769-776.
53. Alonso P., Gratacos M., Menchon J.M., et al. Extensive genotyping of the BDNF and NTRK2 genes define protective haplotypes against obsessive-compulsive disorder. Biol Psychiatry 2008, 63(6):619-628.
54. Hall D., Dhilla A., Charalambous A., et al. Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder. Am J Hum Genet 2003, 73(2):370-376.
55. Wendland J.R., Kruse M.R., Cromer K.R., et al. A large case-control study of common functional SLC6A4 and BDNF variants in obsessive-compulsive disorder. Neuropsychopharmacology 2007, 32(12):2543-2551.
56. Wang Y., Mathews C.A., Li Y., et al. Brain-derived neurotrophic factor (BDNF) plasma levels in drug-naive OCD patients are lower than those in healthy people, but are not lower than those in drug-treated OCD patients. J Affect Disord 2011, 133(1-2):305-310.
57. Dos Santos I.M., Ciulla L., Braga D., et al. Symptom dimensional approach and BDNF in unmedicated obsessive-compulsive patients: an exploratory study. CNS Spectr 2011, [Epub ahead of print].
58. Real E., Gratacos M., Soria V., et al. A brain-derived neurotrophic factor haplotype is associated with therapeutic response in obsessive-compulsive disorder. Biol Psychiatry 2009, 66(7):674-680.
59. Jayarajan R.N., Venkatasubramanian G., Viswanath B., et al. White matter abnormalities in children and adolescents with obsessive-compulsive disorder: a diffusion tensor imaging study. Depress Anxiety 2012, [Epub ahead of print].
60. Macmaster F., Vora A., Easter P., et al. Orbital frontal cortex in treatment-naive pediatric obsessive-compulsive disorder. Psychiatry Res 2010, 181(2):97-100.
61. van den Heuvel O.A., Remijnse P.L., Mataix-Cols D., et al. The major symptom dimensions of obsessive-compulsive disorder are mediated by partially distinct neural systems. Brain 2009, 132(Pt 4):853-868.
62. Szeszko P.R., Ardekani B.A., Ashtari M., et al. White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study. Arch Gen Psychiatry 2005, 62(7):782-790.
63. da Rocha F.F., Correa H., Teixeira A.L. Obsessive-compulsive disorder and immunology: a review. Prog Neuropsychopharmacol Biol Psychiatry 2008, 32(5):1139-1146.
64. Stewart S.E., Platko J., Fagerness J., et al. A genetic family-based association study of OLIG2 in obsessive-compulsive disorder. Arch Gen Psychiatry 2007, 64(2):209-214.
65. Zai G., Bezchlibnyk Y.B., Richter M.A., et al. Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 2004, 129B(1):64-68.
66. Atmaca M., Onalan E., Yildirim H., et al. The association of myelin oligodendrocyte glycoprotein gene and white matter volume in obsessive-compulsive disorder. J Affect Disord 2010, 124(3):309-313.
67. Stewart SE, Yu D, Scharf J, et al. IOCDF Genome-wide association study of obsessive-compulsive disorder. Paper presented at International Congress of Human Genetics 2011; Montreal, Canada.
68. Nestadt G. OCD Genetics: Progress Report from the OCD Collaborative Genetics Association (OCGAS) Study. Paper presented at International OCD Foundation 2011.
69. Merikangas K.R., He J.P., Burstein M., et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry 2010, 49(10):980-989.
70. Gorman J.M., Kent J.M., Sullivan G.M., et al. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 2000, 157(4):493-505.
71. Skre I., Onstad S., Edvardsen J., et al. A family study of anxiety disorders: familial transmission and relationship to mood disorder and psychoactive substance use disorder. Acta Psychiatr Scand 1994, 90(5):366-374.
72. Goldstein R.B., Wickramaratne P.J., Horwath E., et al. Familial aggregation and phenomenology of 'early'-onset (at or before age 20 years) panic disorder. Arch Gen Psychiatry 1997, 54(3):271-278.
73. Fyer A.J., Hamilton S.P., Durner M., et al. A third-pass genome scan in panic disorder: evidence for multiple susceptibility loci. Biol Psychiatry 2006, 60(4):388-401.
74. Maron E., Hettema J.M., Shlik J. Advances in molecular genetics of panic disorder. Mol Psychiatry 2010, 15(7):681-701.
75. Gratacos M, Sahun I, Gallego X, et al. Candidate genes for panic disorder: insight from human and mouse genetic studies. Genes Brain Behav 6(Suppl 1):2-23.
76. Domschke K., Freitag C.M., Kuhlenbaumer G., et al. Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women. Int J Neuropsychopharmacol 2004, 7(2):183-188.
77. Rothe C., Koszycki D., Bradwejn J., et al. Association of the Val158Met catechol O-methyltransferase genetic polymorphism with panic disorder. Neuropsychopharmacology 2006, 31(10):2237-2242.
78. Zintzaras E., Sakelaridis N. Is 472G/A catechol-O-methyl-transferase gene polymorphism related to panic disorder?. Psychiatr Genet 2007, 17(5):267-273.
79. Domschke K., Deckert J., O'Donovan M.C., et al. Meta-analysis of COMT val158met in panic disorder: ethnic heterogeneity and gender specificity. Am J Med Genet B Neuropsychiatr Genet 2007, 144B(5):667-673.
80. Bernier V., Stocco R., Bogusky M.J., et al. Structure-function relationships in the neuropeptide S receptor: molecular consequences of the asthma-associated mutation N107I. J Biol Chem 2006, 281(34):24704-24712.
81. Okamura N., Hashimoto K., Iyo M., et al. Gender-specific association of a functional coding polymorphism in the neuropeptide S receptor gene with panic disorder but not with schizophrenia or attention-deficit/hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2007, 31(7):1444-1448.
82. Domschke K., Reif A., Weber H., et al. Neuropeptide S receptor gene-converging evidence for a role in panic disorder. Mol Psychiatry 2011, 16(9):938-948.
83. Erhardt A., Czibere L., Roeske D., et al. TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies. Mol Psychiatry 2011, 16(6):647-663.
84. Otowa T., Yoshida E., Sugaya N., et al. Genome-wide association study of panic disorder in the Japanese population. J Hum Genet 2009, 54(2):122-126.
85. Otowa T., Tanii H., Sugaya N., et al. Replication of a genome-wide association study of panic disorder in a Japanese population. J Hum Genet 2010, 55(2):91-96.
86. Afifi T.O., Asmundson G.J., Taylor S., et al. The role of genes and environment on trauma exposure and posttraumatic stress disorder symptoms: a review of twin studies. Clin Psychol Rev 2010, 30(1):101-112.
87. Stein M.B., Jang K.L., Taylor S., et al. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. Am J Psychiatry 2002, 159(10):1675-1681.
88. Lyons M.J., Goldberg J., Eisen S.A., et al. Do genes influence exposure to trauma?. A twin study of combat. Am J Med Genet 1993, 48(1):22-27.
89. Yehuda R., Halligan S.L., Bierer L.M. Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring. J Psychiatr Res 2001, 35(5):261-270.
90. Sack W.H., Clarke G.N., Seeley J. Posttraumatic stress disorder across two generations of Cambodian refugees. J Am Acad Child Adolesc Psychiatry 1995, 34(9):1160-1166.
91. Zieker J., Zieker D., Jatzko A., et al. Differential gene expression in peripheral blood of patients suffering from post-traumatic stress disorder. Mol Psychiatry 2007, 12(2):116-118.
92. Koenen K.C. Genetics of posttraumatic stress disorder: review and recommendations for future studies. J Trauma Stress 2007, 20(5):737-750.
93. Jang K.L., Taylor S., Stein M.B., et al. Trauma exposure and stress response: exploration of mechanisms of cause and effect. Twin Res Hum Genet 2007, 10(4):564-572.
94. Hauger R.L., Olivares-Reyes J.A., Dautzenberg F.M., et al. Molecular and cell signaling targets for PTSD pathophysiology and pharmacotherapy. Neuropharmacology 2012, 62(2):705-714.
95. Segman R.H., Shefi N., Goltser-Dubner T., et al. Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Mol Psychiatry 2005, 10(5):425. 500-13.
96. Yehuda R., Cai G., Golier J.A., et al. Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks. Biol Psychiatry 2009, 66(7):708-711.
97. Skelton K., Ressler K.J., Norrholm S.D., et al. PTSD and gene variants: new pathways and new thinking. Neuropharmacology 2012, 62(2):628-637.
98. Mehta D., Gonik M., Klengel T., et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Arch Gen Psychiatry 2011, 68(9):901-910.
99. Ising M., Depping A.M., Siebertz A., et al. Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. Eur J Neurosci 2008, 28(2):389-398.
100. Koenen K.C., Saxe G., Purcell S., et al. Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Mol Psychiatry 2005, 10(12):1058-1059.
101. Binder E.B., Bradley R.G., Liu W., et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008, 299(11):1291-1305.
102. Xie P., Kranzler H.R., Poling J., et al. Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology 2010, 35(8):1684-1692.
103. Sarapas C., Cai G., Bierer L.M., et al. Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks. Dis Markers 2011, 30(2-3):101-110.
104. van Zuiden M., Geuze E., Willemen H.L., et al. Glucocorticoid receptor pathway components predict posttraumatic stress disorder symptom development: a prospective study. Biol Psychiatry 2012, 71(4):309-316.
105. Fanselow M.S., LeDoux J.E. Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 1999, 23(2):229-232.
106. Likhtik E., Pelletier J.G., Paz R., et al. Prefrontal control of the amygdala. J Neurosci 2005, 25(32):7429-7437.
107. Cahill L., Prins B., Weber M., et al. Beta-adrenergic activation and memory for emotional events. Nature 1994, 371(6499):702-704.
108. Ouyang M., Young M.B., Lestini M.M., et al. Redundant catecholamine signaling consolidates fear memory via phospholipase C. J Neurosci 2012, 32(6):1932-1941.
109. Pezawas L., Meyer-Lindenberg A., Drabant E.M., et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nat Neurosci 2005, 8(6):828-834.
110. Cukor J., Spitalnick J., Difede J., et al. Emerging treatments for PTSD. Clin Psychol Rev 2009, 29(8):715-726.
111. Kilpatrick D.G., Koenen K.C., Ruggiero K.J., et al. The serotonin transporter genotype and social support and moderation of posttraumatic stress disorder and depression in hurricane-exposed adults. Am J Psychiatry 2007, 164(11):1693-1699.
112. Koenen K.C., Aiello A.E., Bakshis E., et al. Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by county-level social environment. Am J Epidemiol 2009, 169(6):704-711.
113. Kolassa I.T., Ertl V., Eckart C., et al. Association study of trauma load and SLC6A4 promoter polymorphism in posttraumatic stress disorder: evidence from survivors of the Rwandan genocide. J Clin Psychiatry 2010, 71(5):543-547.
114. Mercer K.B., Orcutt H.K., Quinn J.F., et al. Acute and posttraumatic stress symptoms in a prospective gene × environment study of a university campus shooting. Arch Gen Psychiatry 2012, 69(1):89-97.
115. Schulz-Heik R.J., Schaer M., Eliez S., et al. Catechol-O-methyltransferase Val158Met polymorphism moderates anterior cingulate volume in posttraumatic stress disorder. Biol Psychiatry 2011, 70(11):1091-1096.
116. Kolassa I.T., Kolassa S., Ertl V., et al. The risk of posttraumatic stress disorder after trauma depends on traumatic load and the catechol-O-methyltransferase Val(158)Met polymorphism. Biol Psychiatry 2010, 67(4):304-308.
117. Amstadter A.B., Nugent N.R., Koenen K.C. Genetics of PTSD: fear conditioning as a model for future research. Psychiatr Ann 2009, 39(6):358-367.
118. Bailey J.N., Goenjian A.K., Noble E.P., et al. PTSD and dopaminergic genes, DRD2 and DAT, in multigenerational families exposed to the Spitak earthquake. Psychiatry Res 2010, 178(3):507-510.
119. Amano T., Unal C.T., Pare D. Synaptic correlates of fear extinction in the amygdala. Nat Neurosci 2010, 13(4):489-494.
120. Nelson E.C., Agrawal A., Pergadia M.L., et al. Association of childhood trauma exposure and GABRA2 polymorphisms with risk of posttraumatic stress disorder in adults. Mol Psychiatry 2009, 14(3):234-235.
121. Kamprath K., Marsicano G., Tang J., et al. Cannabinoid CB1 receptor mediates fear extinction via habituation-like processes. J Neurosci 2006, 26(25):6677-6686.
122. Kamprath K., Romo-Parra H., Haring M., et al. Short-term adaptation of conditioned fear responses through endocannabinoid signaling in the central amygdala. Neuropsychopharmacology 2011, 36(3):652-663.
123. Lu A.T., Ogdie M.N., Jarvelin M.R., et al. Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 2008, 147B(8):1488-1494.
124. Amstadter A.B., Koenen K.C., Ruggiero K.J., et al. Variant in RGS2 moderates posttraumatic stress symptoms following potentially traumatic event exposure. J Anxiety Disord 2009, 23(3):369-373.
125. Yehuda R., Bierer L.M. The relevance of epigenetics to PTSD: implications for the DSM-V. J Trauma Stress 2009, 22(5):427-434.
126. Weaver I.C., Cervoni N., Champagne F.A., et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004, 7(8):847-854.
127. McGowan P.O., Sasaki A., D'Alessio A.C., et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009, 12(3):342-348.
128. Ressler K.J., Mercer K.B., Bradley B., et al. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 2011, 470(7335):492-497.
129. Uddin M., Aiello A.E., Wildman D.E., et al. Epigenetic and immune function profiles associated with posttraumatic stress disorder. Proc Natl Acad Sci U S A 2010, 107(20):9470-9475.
130. Rusiecki J.A., Chen L., Srikantan V., et al. DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members. Epigenomics 2012, 4(1):29-40.
131. Cornelis M.C., Nugent N.R., Amstadter A.B., et al. Genetics of post-traumatic stress disorder: review and recommendations for genome-wide association studies. Curr Psychiatry Rep 2010, 12(4):313-326.
132. Gregory A.M., Eley T.C. Genetic influences on anxiety in children: what we've learned and where we're heading. Clin Child Fam Psychol Rev 2007, 10(3):199-212.
133. Eley T.C., Rijsdijk F.V., Perrin S., et al. A multivariate genetic analysis of specific phobia, separation anxiety and social phobia in early childhood. J Abnorm Child Psychol 2008, 36(6):839-848.
134. Ogliari A., Spatola C.A., Pesenti-Gritti P., et al. The role of genes and environment in shaping co-occurrence of DSM-IV defined anxiety dimensions among Italian twins aged 8-17. J Anxiety Disord 2010, 24(4):433-439.
135. Kendler K.S., Gardner C.O., Annas P., et al. The development of fears from early adolesence to young adulthood: a multivariate study. Psychol Med 2008, 38(12):1759-1769.
136. Gelernter J., Page G.P., Stein M.B., et al. Genome-wide linkage scan for loci predisposing to social phobia: evidence for a chromosome 16 risk locus. Am J Psychiatry 2004, 161(1):59-66.
137. Gelernter J., Page G.P., Bonvicini K., et al. A chromosome 14 risk locus for simple phobia: results from a genomewide linkage scan. Mol Psychiatry 2003, 8(1):71-82.
138. Kaabi B., Gelernter J., Woods S.W., et al. Genome scan for loci predisposing to anxiety disorders using a novel multivariate approach: strong evidence for a chromosome 4 risk locus. Am J Hum Genet 2006, 78(4):543-553.
139. Arbelle S., Benjamin J., Golin M., et al. Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism. Am J Psychiatry 2003, 160(4):671-676.
140. Battaglia M., Ogliari A., Zanoni A., et al. Influence of the serotonin transporter promoter gene and shyness on children's cerebral responses to facial expressions. Arch Gen Psychiatry 2005, 62(1):85-94.
141. Schmidt L.A., Fox N.A., Rubin K.H., et al. Molecular genetics of shyness and aggression in preschoolers. Pers Individ Dif 2002, 33(2):227-238.
142. Fox N.A., Nichols K.E., Henderson H.A., et al. Evidence for a gene-environment interaction in predicting behavioral inhibition in middle childhood. Psychol Sci 2005, 16(12):921-926.
143. Koponen E., Voikar V., Riekki R., et al. Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB-PLCgamma pathway, reduced anxiety, and facilitated learning. Mol Cell Neurosci 2004, 26(1):166-181.
144. Zorner B., Wolfer D.P., Brandis D., et al. Forebrain-specific trkB-receptor knockout mice: behaviorally more hyperactive than "depressive.". Biol Psychiatry 2003, 54(10):972-982.
145. Stein M.B., Yang B.Z., Chavira D.A., et al. A common genetic variant in the neurexin superfamily member CNTNAP2 is associated with increased risk for selective mutism and social anxiety-related traits. Biol Psychiatry 2011, 69(9):825-831.
146. Alarcon M., Abrahams B.S., Stone J.L., et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an autism-susceptibility gene. Am J Hum Genet 2008, 82(1):150-159.
147. Hettema J.M., Webb B.T., Guo A.Y., et al. Prioritization and association analysis of murine-derived candidate genes in anxiety-spectrum disorders. Biol Psychiatry 2011, 70(9):888-896.