Imaging and Genetic Approaches to Inform Biomarkers for Anxiety Disorders, Obsessive–Compulsive Disorders, and PSTD

  • Eduard MaronEmail author
  • Chen-Chia Lan
  • David Nutt
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 40)


Anxiety disorders are the most common mental health problem in the world and also claim the highest health care cost among various neuropsychiatric disorders. Anxiety disorders have a chronic and recurrent course and cause significantly negative impacts on patients’ social, personal, and occupational functioning as well as quality of life. Despite their high prevalence rates, anxiety disorders have often been under-diagnosed or misdiagnosed, and consequently under-treated. Even with the correct diagnosis, anxiety disorders are known to be difficult to treat successfully. In order to implement better strategies in diagnosis, prognosis, treatment decision, and early prevention for anxiety disorders, tremendous efforts have been put into studies using genetic and neuroimaging techniques to advance our understandings of the underlying biological mechanisms. In addition to anxiety disorders including panic disorder, generalised anxiety disorder (GAD), specific phobias, social anxiety disorders (SAD), due to overlapping symptom dimensions, obsessive–compulsive disorder (OCD), and post-traumatic stress disorder (PTSD) (which were removed from the anxiety disorder category in DSM-5 to become separate categories) are also included for review of relevant genetic and neuroimaging findings. Although the number of genetic or neuroimaging studies focusing on anxiety disorders is relatively small compare to other psychiatric disorders such as psychotic disorders or mood disorders, various structural abnormalities in the grey or white matter, functional alterations of activity during resting-state or task conditions, molecular changes of neurotransmitter receptors or transporters, and genetic associations have all been reported. With continuing effort, further genetic and neuroimaging research may potentially lead to clinically useful biomarkers for the prevention, diagnosis, and management of these disorders.


Anxiety disorders Biomarkers Brain imaging Genetics 







Serotonin type 1A


Serotonin type 1B


Serotonin type 2A


Serotonin transporter


Serotonin transporter polymorphism


Anterior cingulate cortex


Brodmann area


Brain-derived neurotrophic factor


Bed nucleus of stria terminalis


Blood-oxygen-level dependent




Cognitive behavioural therapy






Dopamine transporter


Dorsolateral prefrontal cortex


Dorsomedial prefrontal cortex


Dopamine D2 receptor


Dopamine D3 receptor


Diagnostic and Statistical Manual of Mental Disorders


Diffusion tensor imaging




Fractional anisotropy


Fractional amplitude of low frequency fluctuations


Functional magnetic resonance imaging


γ-Aminobutyric acid


Generalised anxiety disorder


Glutamate + glutamine


Grey matter


Genome-wide association


Inferior frontal gyrus


Inferior parietal lobule


Inferior temporal gyrus


Monoamine oxidase A


Mid cingulate cortex




Medial temporal lobe


Magnetic resonance imaging


Magnetic resonance spectroscopy


Middle temporal gyrus






Neuropeptide Y


Obsessive–compulsive disorder


Orbitofrontal cortex


Peripheral blood mononuclear cells


Posterior cingulate cortex


Panic disorder


Panic disorder and agoraphobia


Positron emission tomography


Prefrontal cortex


Proteasome modulator 9


Post-traumatic stress disorder


Regional cerebral blood flow


Regional cerebral metabolic rate of glucose uptake


Regulator of G-protein signaling 2


Resting-state functional connectivity


Social anxiety disorder


Superior longitudinal fasciculus


Supplementary motor area


Single nucleotide polymorphisms


Serotonin and norepinephrine reuptake inhibitors


Simple phobias


Single photon emission computed tomography


Superior parietal lobe


Selective serotonin reuptake inhibitors


Superior temporal gyrus


Transmembrane protein 132D


Tryptophan hydroxylase 2


Voxel-based morphometry


Ventrolateral prefrontal cortex


Ventromedial prefrontal cortex


White matter


  1. Abdallah CG, Coplan JD, Jackowski A, Sato JR, Mao X, Shungu DC, Mathew SJ (2013) A pilot study of hippocampal volume and N-acetylaspartate (NAA) as response biomarkers in riluzole-treated patients with GAD. Eur Neuropsychopharmacol 23:276–284. CrossRefPubMedGoogle Scholar
  2. Adams KH, Hansen ES, Pinborg LH, Hasselbalch SG, Svarer C, Holm S, Bolwig TG, Knudsen GM (2005) Patients with obsessive-compulsive disorder have increased 5-HT2A receptor binding in the caudate nuclei. Int J Neuropsychopharmacol 8:391–401. CrossRefPubMedGoogle Scholar
  3. Ahs F, Furmark T, Michelgård A, Långström B, Appel L, Wolf OT, Kirschbaum C, Fredrikson M (2006) Hypothalamic blood flow correlates positively with stress-induced cortisol levels in subjects with social anxiety disorder. Psychosom Med 68:859–862. CrossRefPubMedGoogle Scholar
  4. Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, de Girolamo G, Graaf R, Demyttenaere K, Gasquet I, Haro JM, Katz SJ, Kessler RC, Kovess V, Lépine JP, Ormel J, Polidori G, Russo LJ, Vilagut G, Almansa J, Arbabzadeh-Bouchez S, Autonell J, Bernal M, Buist-Bouwman MA, Codony M, Domingo-Salvany A, Ferrer M, Joo SS, Martínez-Alonso M, Matschinger H, Mazzi F, Morgan Z, Morosini P, Palacín C, Romera B, Taub N, Vollebergh WAM, ESEMeD/MHEDEA 2000 Investigators, European Study of the Epidemiology of Mental Disorders (ESEMeD) Project (2004) Psychotropic drug utilization in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatr Scand Suppl 420:55–64. CrossRefGoogle Scholar
  5. Amstadter AB, Koenen KC, Ruggiero KJ, Acierno R, Galea S, Kilpatrick DG, Gelernter J (2010) NPY moderates the relation between hurricane exposure and generalized anxiety disorder in an epidemiologic sample of hurricane-exposed adults. Depress Anxiety 27:270–275. CrossRefPubMedCentralPubMedGoogle Scholar
  6. Andersson E, Rück C, Lavebratt C, Hedman E, Schalling M, Lindefors N, Eriksson E, Carlbring P, Andersson G, Furmark T (2013) Genetic polymorphisms in monoamine systems and outcome of cognitive behavior therapy for social anxiety disorder. PLoS One 8:e79015. CrossRefPubMedCentralPubMedGoogle Scholar
  7. Anticevic A, Hu S, Zhang S, Savic A, Billingslea E, Wasylink S, Repovs G, Cole MW, Bednarski S, Krystal JH, Bloch MH, Li C-SR, Pittenger C (2014) Global resting-state functional magnetic resonance imaging analysis identifies frontal cortex, striatal, and cerebellar dysconnectivity in obsessive-compulsive disorder. Biol Psychiatry 75:595–605. CrossRefPubMedGoogle Scholar
  8. Asami T, Hayano F, Nakamura M, Yamasue H, Uehara K, Otsuka T, Roppongi T, Nihashi N, Inoue T, Hirayasu Y (2008) Anterior cingulate cortex volume reduction in patients with panic disorder. Psychiatry Clin Neurosci 62:322–330. CrossRefPubMedGoogle Scholar
  9. Asami T, Yamasue H, Hayano F, Nakamura M, Uehara K, Otsuka T, Roppongi T, Nihashi N, Inoue T, Hirayasu Y (2009) Sexually dimorphic gray matter volume reduction in patients with panic disorder. Psychiatry Res 173:128–134. CrossRefPubMedGoogle Scholar
  10. Ashley-Koch AE, Garrett ME, Gibson J, Liu Y, Dennis MF, Kimbrel NA, Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup, Beckham JC, Hauser MA (2015) Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans. J Affect Disord 184:225–234. CrossRefPubMedCentralPubMedGoogle Scholar
  11. Atmaca M, Yildirim H, Gurok MG, Akyol M (2012) Orbito-frontal cortex volumes in panic disorder. Psychiat Invest 9:408–412. CrossRefGoogle Scholar
  12. Aupperle RL, Hale LR, Chambers RJ, Cain SE, Barth FX, Sharp SC, Denney DR, Savage CR (2009) An fMRI study examining effects of acute D-cycloserine during symptom provocation in spider phobia. CNS Spectr 14:556–571CrossRefPubMedGoogle Scholar
  13. Ball TM, Ramsawh HJ, Campbell-Sills L, Paulus MP, Stein MB (2013) Prefrontal dysfunction during emotion regulation in generalized anxiety and panic disorders. Psychol Med 43:1475–1486. CrossRefPubMedGoogle Scholar
  14. Ball TM, Stein MB, Ramsawh HJ, Campbell-Sills L, Paulus MP (2014) Single-subject anxiety treatment outcome prediction using functional neuroimaging. Neuropsychopharmacology 39:1254–1261. CrossRefPubMedCentralPubMedGoogle Scholar
  15. Banca P, Voon V, Vestergaard MD, Philipiak G, Almeida I, Pocinho F, Relvas J, Castelo-Branco M (2015) Imbalance in habitual versus goal directed neural systems during symptom provocation in obsessive-compulsive disorder. Brain 138:798–811. CrossRefPubMedCentralPubMedGoogle Scholar
  16. Bandelow B, Baldwin D, Abelli M, Altamura C, Dell’Osso B, Domschke K, Fineberg NA, Grünblatt E, Jarema M, Maron E, Nutt D, Pini S, Vaghi MM, Wichniak A, Zai G, Riederer P (2016) Biological markers for anxiety disorders, OCD and PTSD – a consensus statement. Part I: neuroimaging and genetics. World J Biol Psychiatry 17:321–365. CrossRefPubMedGoogle Scholar
  17. Banks GP, Mikell CB, Youngerman BE, Henriques B, Kelly KM, Chan AK, Herrera D, Dougherty DD, Eskandar EN, Sheth SA (2015) Neuroanatomical characteristics associated with response to dorsal anterior cingulotomy for obsessive-compulsive disorder. JAMA Psychiat 72:127–135. CrossRefGoogle Scholar
  18. Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy DL, Cohen RM (1990) Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine. Arch Gen Psychiatry 47:840–848CrossRefPubMedGoogle Scholar
  19. Berney A, Leyton M, Gravel P, Sibon I, Sookman D, Rosa Neto P, Diksic M, Nakai A, Pinard G, Todorov C, Okazawa H, Blier P, Nordahl TE, Benkelfat C (2011) Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients with obsessive-compulsive disorder. Arch Gen Psychiatry 68:732–741. CrossRefPubMedCentralPubMedGoogle Scholar
  20. Blair K, Shaywitz J, Smith BW, Rhodes R, Geraci M, Jones M, McCaffrey D, Vythilingam M, Finger E, Mondillo K, Jacobs M, Charney DS, Blair RJR, Drevets WC, Pine DS (2008) Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am J Psychiatry 165:1193–1202. CrossRefPubMedCentralPubMedGoogle Scholar
  21. Blair KS, Geraci M, Smith BW, Hollon N, DeVido J, Otero M, Blair JR, Pine DS (2012) Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in generalized social phobia, generalized anxiety disorder, and comorbid generalized social phobia/generalized anxiety disorder. Biol Psychiatry 72:476–482. CrossRefPubMedCentralPubMedGoogle Scholar
  22. Boedhoe PSW, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, Benedetti F, Beucke JC, Bollettini I, Bose A, Brem S, Calvo A, Cheng Y, Cho KIK, Dallaspezia S, Denys D, Fitzgerald KD, Fouche J-P, Giménez M, Gruner P, Hanna GL, Hibar DP, Hoexter MQ, Hu H, Huyser C, Ikari K, Jahanshad N, Kathmann N, Kaufmann C, Koch K, Kwon JS, Lazaro L, Liu Y, Lochner C, Marsh R, Martínez-Zalacaín I, Mataix-Cols D, Menchón JM, Minuzzi L, Nakamae T, Nakao T, Narayanaswamy JC, Piras F, Piras F, Pittenger C, Reddy YCJ, Sato JR, Simpson HB, Soreni N, Soriano-Mas C, Spalletta G, Stevens MC, Szeszko PR, Tolin DF, Venkatasubramanian G, Walitza S, Wang Z, van Wingen GA, Xu J, Xu X, Yun J-Y, Zhao Q, ENIGMA OCD Working Group, Thompson PM, Stein DJ, van den Heuvel OA (2017) Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry 174:60–69. CrossRefPubMedGoogle Scholar
  23. Bonne O, Bain E, Neumeister A, Nugent AC, Vythilingam M, Carson RE, Luckenbaugh DA, Eckelman W, Herscovitch P, Drevets WC, Charney DS (2005) No change in serotonin type 1A receptor binding in patients with posttraumatic stress disorder. Am J Psychiatry 162:383–385. CrossRefPubMedGoogle Scholar
  24. Brandl EJ, Tiwari AK, Zhou X, Deluce J, Kennedy JL, Müller DJ, Richter MA (2014) Influence of CYP2D6 and CYP2C19 gene variants on antidepressant response in obsessive-compulsive disorder. Pharmacogenomics J 14:176–181. CrossRefPubMedGoogle Scholar
  25. Breiter HC, Rauch SL, Kwong KK, Baker JR, Weisskoff RM, Kennedy DN, Kendrick AD, Davis TL, Jiang A, Cohen MS, Stern CE, Belliveau JW, Baer L, O’Sullivan RL, Savage CR, Jenike MA, Rosen BR (1996) Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. Arch Gen Psychiatry 53:595–606CrossRefPubMedGoogle Scholar
  26. Bremner JD (2001) Hypotheses and controversies related to effects of stress on the hippocampus: an argument for stress-induced damage to the hippocampus in patients with posttraumatic stress disorder. Hippocampus 11:75–81. Discussion 82. CrossRefPubMedGoogle Scholar
  27. Bremner JD, Innis RB, Southwick SM, Staib L, Zoghbi S, Charney DS (2000a) Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder. Am J Psychiatry 157:1120–1126. CrossRefPubMedGoogle Scholar
  28. Bremner JD, Innis RB, White T, Fujita M, Silbersweig D, Goddard AW, Staib L, Stern E, Cappiello A, Woods S, Baldwin R, Charney DS (2000b) SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder. Biol Psychiatry 47:96–106CrossRefPubMedGoogle Scholar
  29. Brennan BP, Rauch SL, Jensen JE, Pope HG (2013) A critical review of magnetic resonance spectroscopy studies of obsessive-compulsive disorder. Biol Psychiatry 73:24–31. CrossRefPubMedGoogle Scholar
  30. Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR (1998) FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder. Psychiatry Res 84:1–6CrossRefPubMedGoogle Scholar
  31. Brown GG, Ostrowitzki S, Stein MB, von Kienlin M, Liu TT, Simmons A, Wierenga C, Stein OY, Bruns A, Bischoff-Grethe A, Paulus M (2015) Temporal profile of brain response to alprazolam in patients with generalized anxiety disorder. Psychiatry Res 233:394–401. CrossRefPubMedGoogle Scholar
  32. Bryant RA, Felmingham K, Kemp A, Das P, Hughes G, Peduto A, Williams L (2008) Amygdala and ventral anterior cingulate activation predicts treatment response to cognitive behaviour therapy for post-traumatic stress disorder. Psychol Med 38:555–561. CrossRefPubMedGoogle Scholar
  33. Bryant RA, Felmingham KL, Falconer EM, Pe Benito L, Dobson-Stone C, Pierce KD, Schofield PR (2010) Preliminary evidence of the short allele of the serotonin transporter gene predicting poor response to cognitive behavior therapy in posttraumatic stress disorder. Biol Psychiatry 67:1217–1219. CrossRefPubMedGoogle Scholar
  34. Bystritsky A, Pontillo D, Powers M, Sabb FW, Craske MG, Bookheimer SY (2001) Functional MRI changes during panic anticipation and imagery exposure. Neuroreport 12:3953–3957CrossRefPubMedGoogle Scholar
  35. Cameron OG, Huang GC, Nichols T, Koeppe RA, Minoshima S, Rose D, Frey KA (2007) Reduced gamma-aminobutyric acid(A)-benzodiazepine binding sites in insular cortex of individuals with panic disorder. Arch Gen Psychiatry 64:793–800. CrossRefPubMedGoogle Scholar
  36. Cannon DM, Klaver JM, Klug SA, Carlson PJ, Luckenbaugh DA, Ichise M, Drevets WC (2013) Gender-specific abnormalities in the serotonin transporter system in panic disorder. Int J Neuropsychopharmacol 16:733–743. CrossRefPubMedGoogle Scholar
  37. Canu E, Kostić M, Agosta F, Munjiza A, Ferraro PM, Pesic D, Copetti M, Peljto A, Lecic Tosevski D, Filippi M (2015) Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity. J Neurol 262:1255–1265. CrossRefPubMedGoogle Scholar
  38. Carey PD, Warwick J, Niehaus DJH, van der Linden G, van Heerden BB, Harvey BH, Seedat S, Stein DJ (2004) Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram. BMC Psychiatry 4:30. CrossRefPubMedCentralPubMedGoogle Scholar
  39. Cervenka S, Hedman E, Ikoma Y, Djurfeldt DR, Rück C, Halldin C, Lindefors N (2012) Changes in dopamine D2-receptor binding are associated to symptom reduction after psychotherapy in social anxiety disorder. Transl Psychiatry 2:e120. CrossRefPubMedCentralPubMedGoogle Scholar
  40. Cha J, Carlson JM, Dedora DJ, Greenberg T, Proudfit GH, Mujica-Parodi LR (2014a) Hyper-reactive human ventral tegmental area and aberrant mesocorticolimbic connectivity in overgeneralization of fear in generalized anxiety disorder. J Neurosci 34:5855–5860. CrossRefPubMedGoogle Scholar
  41. Cha J, Greenberg T, Carlson JM, Dedora DJ, Hajcak G, Mujica-Parodi LR (2014b) Circuit-wide structural and functional measures predict ventromedial prefrontal cortex fear generalization: implications for generalized anxiety disorder. J Neurosci 34:4043–4053. CrossRefPubMedGoogle Scholar
  42. Chen AC, Etkin A (2013) Hippocampal network connectivity and activation differentiates post-traumatic stress disorder from generalized anxiety disorder. Neuropsychopharmacology 38:1889–1898. CrossRefPubMedCentralPubMedGoogle Scholar
  43. Chen S-D, Sun X-Y, Niu W, Kong L-M, He M-J, Fan H-M, Li W-S, Zhong A-F, Zhang L-Y, Lu J (2016) Correlation between the level of microRNA expression in peripheral blood mononuclear cells and symptomatology in patients with generalized anxiety disorder. Compr Psychiatry 69:216–224. CrossRefPubMedGoogle Scholar
  44. Cheng B, Cai W, Wang X, Lei D, Guo Y, Yang X, Wu Q, Gong J, Gong Q, Ning G (2016) Brain gray matter abnormalities in first-episode, treatment-naive children with obsessive-compulsive disorder. Front Behav Neurosci 10:141. CrossRefPubMedCentralPubMedGoogle Scholar
  45. Cui H, Zhang J, Liu Y, Li Q, Li H, Zhang L, Hu Q, Cheng W, Luo Q, Li J, Li W, Wang J, Feng J, Li C, Northoff G (2016) Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder. Hum Brain Mapp 37:1459–1473. CrossRefPubMedGoogle Scholar
  46. Daniels JK, Lamke J-P, Gaebler M, Walter H, Scheel M (2013) White matter integrity and its relationship to PTSD and childhood trauma – a systematic review and meta-analysis. Depress Anxiety 30:207–216. CrossRefPubMedGoogle Scholar
  47. de Wit SJ, Alonso P, Schweren L, Mataix-Cols D, Lochner C, Menchón JM, Stein DJ, Fouche J-P, Soriano-Mas C, Sato JR, Hoexter MQ, Denys D, Nakamae T, Nishida S, Kwon JS, Jang JH, Busatto GF, Cardoner N, Cath DC, Fukui K, Jung WH, Kim SN, Miguel EC, Narumoto J, Phillips ML, Pujol J, Remijnse PL, Sakai Y, Shin NY, Yamada K, Veltman DJ, van den Heuvel OA (2014) Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive-compulsive disorder. Am J Psychiatry 171:340–349. CrossRefPubMedGoogle Scholar
  48. Deakin JF, Graeff FG (1991) 5-HT and mechanisms of defence. J Psychopharmacol (Oxf) 5:305–315. CrossRefGoogle Scholar
  49. Del Casale A, Rapinesi C, Kotzalidis GD, De Rossi P, Curto M, Janiri D, Criscuolo S, Alessi MC, Ferri VR, De Giorgi R, Sani G, Ferracuti S, Girardi P, Brugnoli R (2016) Executive functions in obsessive-compulsive disorder: an activation likelihood estimate meta-analysis of fMRI studies. World J Biol Psychiatry 17:378–393. CrossRefPubMedGoogle Scholar
  50. Demenescu LR, Kortekaas R, Cremers HR, Renken RJ, van Tol MJ, van der Wee NJA, Veltman DJ, den Boer JA, Roelofs K, Aleman A (2013) Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder. J Psychiatr Res 47:1024–1031. CrossRefPubMedGoogle Scholar
  51. Dickie EW, Brunet A, Akerib V, Armony JL (2013) Anterior cingulate cortical thickness is a stable predictor of recovery from post-traumatic stress disorder. Psychol Med 43:645–653. CrossRefPubMedGoogle Scholar
  52. Ding J, Chen H, Qiu C, Liao W, Warwick JM, Duan X, Zhang W, Gong Q (2011) Disrupted functional connectivity in social anxiety disorder: a resting-state fMRI study. Magn Reson Imaging 29:701–711. CrossRefPubMedGoogle Scholar
  53. Dodhia S, Hosanagar A, Fitzgerald DA, Labuschagne I, Wood AG, Nathan PJ, Phan KL (2014) Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder. Neuropsychopharmacology 39:2061–2069. CrossRefPubMedCentralPubMedGoogle Scholar
  54. Doehrmann O, Ghosh SS, Polli FE, Reynolds GO, Horn F, Keshavan A, Triantafyllou C, Saygin ZM, Whitfield-Gabrieli S, Hofmann SG, Pollack M, Gabrieli JD (2013) Predicting treatment response in social anxiety disorder from functional magnetic resonance imaging. JAMA Psychiat 70:87–97. CrossRefGoogle Scholar
  55. Dresler T, Hindi Attar C, Spitzer C, Löwe B, Deckert J, Büchel C, Ehlis A-C, Fallgatter AJ (2012) Neural correlates of the emotional Stroop task in panic disorder patients: an event-related fMRI study. J Psychiatr Res 46:1627–1634. CrossRefPubMedGoogle Scholar
  56. Engel KR, Obst K, Bandelow B, Dechent P, Gruber O, Zerr I, Ulrich K, Wedekind D (2016) Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls. Eur Arch Psychiatry Clin Neurosci 266:557–566. CrossRefPubMedGoogle Scholar
  57. Etkin A, Schatzberg AF (2011) Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders. Am J Psychiatry 168:968–978. CrossRefPubMedGoogle Scholar
  58. Etkin A, Wager TD (2007) Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 164:1476–1488. CrossRefPubMedCentralPubMedGoogle Scholar
  59. Etkin A, Prater KE, Schatzberg AF, Menon V, Greicius MD (2009) Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch Gen Psychiatry 66:1361–1372. CrossRefGoogle Scholar
  60. Etkin A, Prater KE, Hoeft F, Menon V, Schatzberg AF (2010) Failure of anterior cingulate activation and connectivity with the amygdala during implicit regulation of emotional processing in generalized anxiety disorder. Am J Psychiatry 167:545–554. CrossRefPubMedCentralPubMedGoogle Scholar
  61. Evans KC, Simon NM, Dougherty DD, Hoge EA, Worthington JJ, Chow C, Kaufman RE, Gold AL, Fischman AJ, Pollack MH, Rauch SL (2009) A PET study of tiagabine treatment implicates ventral medial prefrontal cortex in generalized social anxiety disorder. Neuropsychopharmacology 34:390–398. CrossRefPubMedGoogle Scholar
  62. Faravelli C, Paterniti S, Scarpato A (1995) 5-year prospective, naturalistic follow-up study of panic disorder. Compr Psychiatry 36:271–277CrossRefPubMedGoogle Scholar
  63. Faria V, Ahs F, Appel L, Linnman C, Bani M, Bettica P, Pich EM, Wahlstedt K, Fredrikson M, Furmark T (2014) Amygdala-frontal couplings characterizing SSRI and placebo response in social anxiety disorder. Int J Neuropsychopharmacol 17:1149–1157. CrossRefPubMedGoogle Scholar
  64. Feldker K, Heitmann CY, Neumeister P, Bruchmann M, Vibrans L, Zwitserlood P, Straube T (2016) Brain responses to disorder-related visual threat in panic disorder. Hum Brain Mapp 37:4439–4453. CrossRefPubMedGoogle Scholar
  65. Felmingham KL, Dobson-Stone C, Schofield PR, Quirk GJ, Bryant RA (2013) The brain-derived neurotrophic factor Val66Met polymorphism predicts response to exposure therapy in posttraumatic stress disorder. Biol Psychiatry 73:1059–1063. CrossRefPubMedCentralPubMedGoogle Scholar
  66. Figee M, Luigjes J, Smolders R, Valencia-Alfonso C-E, van Wingen G, de Kwaasteniet B, Mantione M, Ooms P, de Koning P, Vulink N, Levar N, Droge L, van den Munckhof P, Schuurman PR, Nederveen A, van den Brink W, Mazaheri A, Vink M, Denys D (2013) Deep brain stimulation restores frontostriatal network activity in obsessive-compulsive disorder. Nat Neurosci 16:386–387. CrossRefPubMedGoogle Scholar
  67. Fineberg NA, Reghunandanan S, Brown A, Pampaloni I (2013) Pharmacotherapy of obsessive-compulsive disorder: evidence-based treatment and beyond. Aust N Z J Psychiatry 47:121–141. CrossRefPubMedGoogle Scholar
  68. Fisler MS, Federspiel A, Horn H, Dierks T, Schmitt W, Wiest R, de Quervain DJ-F, Soravia LM (2013) Spider phobia is associated with decreased left amygdala volume: a cross-sectional study. BMC Psychiatry 13:70. CrossRefPubMedCentralPubMedGoogle Scholar
  69. Fontaine R, Breton G, Déry R, Fontaine S, Elie R (1990) Temporal lobe abnormalities in panic disorder: an MRI study. Biol Psychiatry 27:304–310CrossRefPubMedGoogle Scholar
  70. Fonzo GA, Ramsawh HJ, Flagan TM, Sullivan SG, Simmons AN, Paulus MP, Stein MB (2014) Cognitive-behavioral therapy for generalized anxiety disorder is associated with attenuation of limbic activation to threat-related facial emotions. J Affect Disord 169:76–85. CrossRefPubMedCentralPubMedGoogle Scholar
  71. Fonzo GA, Goodkind MS, Oathes DJ, Zaiko YV, Harvey M, Peng KK, Weiss ME, Thompson AL, Zack SE, Lindley SE, Arnow BA, Jo B, Gross JJ, Rothbaum BO, Etkin A (2017a) PTSD psychotherapy outcome predicted by brain activation during emotional reactivity and regulation. Am J Psychiatry 174:1163–1174. CrossRefPubMedCentralPubMedGoogle Scholar
  72. Fonzo GA, Goodkind MS, Oathes DJ, Zaiko YV, Harvey M, Peng KK, Weiss ME, Thompson AL, Zack SE, Mills-Finnerty CE, Rosenberg BM, Edelstein R, Wright RN, Kole CA, Lindley SE, Arnow BA, Jo B, Gross JJ, Rothbaum BO, Etkin A (2017b) Selective effects of psychotherapy on frontopolar cortical function in PTSD. Am J Psychiatry 174:1175–1184. CrossRefPubMedCentralPubMedGoogle Scholar
  73. Freitas-Ferrari MC, Hallak JEC, Trzesniak C, Filho AS, Machado-de-Sousa JP, Chagas MHN, Nardi AE, Crippa JAS (2010) Neuroimaging in social anxiety disorder: a systematic review of the literature. Prog Neuro-Psychopharmacol Biol Psychiatry 34:565–580. CrossRefGoogle Scholar
  74. Frick A, Howner K, Fischer H, Eskildsen SF, Kristiansson M, Furmark T (2013) Cortical thickness alterations in social anxiety disorder. Neurosci Lett 536:52–55. CrossRefPubMedGoogle Scholar
  75. Frick A, Åhs F, Engman J, Jonasson M, Alaie I, Björkstrand J, Frans Ö, Faria V, Linnman C, Appel L, Wahlstedt K, Lubberink M, Fredrikson M, Furmark T (2015a) Serotonin synthesis and reuptake in social anxiety disorder: a positron emission tomography study. JAMA Psychiat 72:794–802. CrossRefGoogle Scholar
  76. Frick A, Ahs F, Linnman C, Jonasson M, Appel L, Lubberink M, Långström B, Fredrikson M, Furmark T (2015b) Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [11C]GR205171. Transl Psychiatry 5:e597. CrossRefPubMedCentralPubMedGoogle Scholar
  77. Frick A, Åhs F, Appel L, Jonasson M, Wahlstedt K, Bani M, Merlo Pich E, Bettica P, Långström B, Lubberink M, Fredrikson M, Furmark T (2016a) Reduced serotonin synthesis and regional cerebral blood flow after anxiolytic treatment of social anxiety disorder. Eur Neuropsychopharmacol 26:1775–1783. CrossRefPubMedGoogle Scholar
  78. Frick A, Åhs F, Palmquist ÅM, Pissiota A, Wallenquist U, Fernandez M, Jonasson M, Appel L, Frans Ö, Lubberink M, Furmark T, von Knorring L, Fredrikson M (2016b) Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study. Mol Psychiatry 21:1400–1407. CrossRefPubMedGoogle Scholar
  79. Fujimura Y, Yasuno F, Farris A, Liow J-S, Geraci M, Drevets W, Pine DS, Ghose S, Lerner A, Hargreaves R, Burns HD, Morse C, Pike VW, Innis RB (2009) Decreased neurokinin-1 (substance P) receptor binding in patients with panic disorder: positron emission tomographic study with [18F]SPA-RQ. Biol Psychiatry 66:94–97. CrossRefPubMedCentralPubMedGoogle Scholar
  80. Fujiwara A, Yoshida T, Otsuka T, Hayano F, Asami T, Narita H, Nakamura M, Inoue T, Hirayasu Y (2011) Midbrain volume increase in patients with panic disorder. Psychiatry Clin Neurosci 65:365–373. CrossRefPubMedGoogle Scholar
  81. Furmark T, Appel L, Michelgård A, Wahlstedt K, Ahs F, Zancan S, Jacobsson E, Flyckt K, Grohp M, Bergström M, Pich EM, Nilsson L-G, Bani M, Långström B, Fredrikson M (2005) Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo. Biol Psychiatry 58:132–142. CrossRefPubMedGoogle Scholar
  82. Furmark T, Marteinsdottir I, Frick A, Heurling K, Tillfors M, Appel L, Antoni G, Hartvig P, Fischer H, Långström B, Eriksson E, Fredrikson M (2016) Serotonin synthesis rate and the tryptophan hydroxylase-2: G-703T polymorphism in social anxiety disorder. J Psychopharmacol (Oxf) 30:1028–1035. CrossRefGoogle Scholar
  83. Gelernter J, Page GP, Stein MB, Woods SW (2004) Genome-wide linkage scan for loci predisposing to social phobia: evidence for a chromosome 16 risk locus. Am J Psychiatry 161:59–66. CrossRefPubMedGoogle Scholar
  84. Gentili C, Cristea IA, Angstadt M, Klumpp H, Tozzi L, Phan KL, Pietrini P (2016) Beyond emotions: a meta-analysis of neural response within face processing system in social anxiety. Exp Biol Med 241:225–237. CrossRefGoogle Scholar
  85. Gingnell M, Frick A, Engman J, Alaie I, Björkstrand J, Faria V, Carlbring P, Andersson G, Reis M, Larsson E-M, Wahlstedt K, Fredrikson M, Furmark T (2016) Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial. Br J Psychiatry 209:229–235. CrossRefPubMedGoogle Scholar
  86. Goossens L, Sunaert S, Peeters R, Griez EJL, Schruers KRJ (2007) Amygdala hyperfunction in phobic fear normalizes after exposure. Biol Psychiatry 62:1119–1125. CrossRefPubMedGoogle Scholar
  87. Gorka SM, Nelson BD, Phan KL, Shankman SA (2014) Insula response to unpredictable and predictable aversiveness in individuals with panic disorder and comorbid depression. Biol Mood Anxiety Disord 4:9. CrossRefPubMedCentralPubMedGoogle Scholar
  88. Gorka SM, Fitzgerald DA, Labuschagne I, Hosanagar A, Wood AG, Nathan PJ, Phan KL (2015) Oxytocin modulation of amygdala functional connectivity to fearful faces in generalized social anxiety disorder. Neuropsychopharmacology 40:278–286. CrossRefPubMedGoogle Scholar
  89. Gorman JM, Kent JM, Sullivan GM, Coplan JD (2000) Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 157:493–505. CrossRefPubMedGoogle Scholar
  90. Göttlich M, Krämer UM, Kordon A, Hohagen F, Zurowski B (2015) Resting-state connectivity of the amygdala predicts response to cognitive behavioral therapy in obsessive compulsive disorder. Biol Psychol 111:100–109. CrossRefPubMedGoogle Scholar
  91. Gragnoli C (2014) Proteasome modulator 9 gene SNPs, responsible for anti-depressant response, are in linkage with generalized anxiety disorder. J Cell Physiol 229:1157–1159. CrossRefPubMedGoogle Scholar
  92. Gross-Isseroff R, Kushnir T, Hermesh H, Marom S, Weizman A, Manor D (2010) Alteration learning in social anxiety disorder: an fMRI study. World J Biol Psychiatry 11:352–356. CrossRefPubMedGoogle Scholar
  93. Hahn T, Kircher T, Straube B, Wittchen H-U, Konrad C, Ströhle A, Wittmann A, Pfleiderer B, Reif A, Arolt V, Lueken U (2015) Predicting treatment response to cognitive behavioral therapy in panic disorder with agoraphobia by integrating local neural information. JAMA Psychiat 72:68–74. CrossRefGoogle Scholar
  94. Han DH, Renshaw PF, Dager SR, Chung A, Hwang J, Daniels MA, Lee YS, Lyoo IK (2008) Altered cingulate white matter connectivity in panic disorder patients. J Psychiatr Res 42:399–407. CrossRefPubMedGoogle Scholar
  95. Harnett NG, Wood KH, Ference EW, Reid MA, Lahti AC, Knight AJ, Knight DC (2017) Glutamate/glutamine concentrations in the dorsal anterior cingulate vary with post-traumatic stress disorder symptoms. J Psychiatr Res 91:169–176. CrossRefPubMedGoogle Scholar
  96. Harrison BJ, Soriano-Mas C, Pujol J, Ortiz H, López-Solà M, Hernández-Ribas R, Deus J, Alonso P, Yücel M, Pantelis C, Menchon JM, Cardoner N (2009) Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Arch Gen Psychiatry 66:1189–1200. CrossRefPubMedGoogle Scholar
  97. Harrison BJ, Pujol J, Cardoner N, Deus J, Alonso P, López-Solà M, Contreras-Rodríguez O, Real E, Segalàs C, Blanco-Hinojo L, Menchon JM, Soriano-Mas C (2013) Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder. Biol Psychiatry 73:321–328. CrossRefPubMedGoogle Scholar
  98. Hasler G, Nugent AC, Carlson PJ, Carson RE, Geraci M, Drevets WC (2008) Altered cerebral gamma-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry 65:1166–1175. CrossRefPubMedGoogle Scholar
  99. Hayano F, Nakamura M, Asami T, Uehara K, Yoshida T, Roppongi T, Otsuka T, Inoue T, Hirayasu Y (2009) Smaller amygdala is associated with anxiety in patients with panic disorder. Psychiatry Clin Neurosci 63:266–276. CrossRefPubMedGoogle Scholar
  100. Hettema JM, Neale MC, Kendler KS (2001) A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 158:1568–1578. CrossRefPubMedGoogle Scholar
  101. Hilbert K, Evens R, Maslowski NI, Wittchen H-U, Lueken U (2015a) Neurostructural correlates of two subtypes of specific phobia: a voxel-based morphometry study. Psychiatry Res 231:168–175. CrossRefPubMedGoogle Scholar
  102. Hilbert K, Pine DS, Muehlhan M, Lueken U, Steudte-Schmiedgen S, Beesdo-Baum K (2015b) Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization. Psychiatry Res 234:314–320. CrossRefPubMedCentralPubMedGoogle Scholar
  103. Hirschfeld RMA (2001) The comorbidity of major depression and anxiety disorders: recognition and management in primary care. Prim Care Companion J Clin Psychiatry 3:244–254CrossRefPubMedGoogle Scholar
  104. Ho Pian KL, van Megen HJGM, Ramsey NF, Mandl R, van Rijk PP, Wynne HJ, Westenberg HGM (2005) Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine. Psychiatry Res 138:89–97. CrossRefPubMedGoogle Scholar
  105. Hoehn-Saric R, Schlund MW, Wong SHY (2004) Effects of citalopram on worry and brain activation in patients with generalized anxiety disorder. Psychiatry Res 131:11–21. CrossRefPubMedGoogle Scholar
  106. Hoexter MQ, Dougherty DD, Shavitt RG, D’Alcante CC, Duran FLS, Lopes AC, Diniz JB, Batistuzzo MC, Evans KC, Bressan RA, Busatto GF, Miguel EC (2013) Differential prefrontal gray matter correlates of treatment response to fluoxetine or cognitive-behavioral therapy in obsessive-compulsive disorder. Eur Neuropsychopharmacol 23:569–580. CrossRefPubMedGoogle Scholar
  107. Holmes SE, Girgenti MJ, Davis MT, Pietrzak RH, DellaGioia N, Nabulsi N, Matuskey D, Southwick S, Duman RS, Carson RE, Krystal JH, Esterlis I, Traumatic Stress Brain Study Group (2017) Altered metabotropic glutamate receptor 5 markers in PTSD: in vivo and postmortem evidence. Proc Natl Acad Sci U S A 114:8390–8395. CrossRefPubMedCentralPubMedGoogle Scholar
  108. Hölzel BK, Hoge EA, Greve DN, Gard T, Creswell JD, Brown KW, Barrett LF, Schwartz C, Vaitl D, Lazar SW (2013) Neural mechanisms of symptom improvements in generalized anxiety disorder following mindfulness training. Neuroimage Clin 2:448–458. CrossRefPubMedCentralPubMedGoogle Scholar
  109. Howe AS, Buttenschøn HN, Bani-Fatemi A, Maron E, Otowa T, Erhardt A, Binder EB, Gregersen NO, Mors O, Woldbye DP, Domschke K, Reif A, Shlik J, Kõks S, Kawamura Y, Miyashita A, Kuwano R, Tokunaga K, Tanii H, Smoller JW, Sasaki T, Koszycki D, De Luca V (2016) Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways. Mol Psychiatry 21:665–679. CrossRefPubMedGoogle Scholar
  110. Hsieh H-J, Lue K-H, Tsai H-C, Lee C-C, Chen S-Y, Kao P-F (2014) L-3,4-Dihydroxy-6-[F-18]fluorophenylalanine positron emission tomography demonstrating dopaminergic system abnormality in the brains of obsessive-compulsive disorder patients. Psychiatry Clin Neurosci 68:292–298. CrossRefPubMedGoogle Scholar
  111. International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS) (2017) Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis. Mol Psychiatry. CrossRefGoogle Scholar
  112. Irle E, Ruhleder M, Lange C, Seidler-Brandler U, Salzer S, Dechent P, Weniger G, Leibing E, Leichsenring F (2010) Reduced amygdalar and hippocampal size in adults with generalized social phobia. J Psychiatry Neurosci 35:126–131CrossRefPubMedGoogle Scholar
  113. Kang E-H, Park J-E, Lee K-H, Cho Y-S, Kim J-J, Yu B-H (2012) Regional brain metabolism and treatment response in panic disorder patients: an [18F]FDG-PET study. Neuropsychobiology 66:106–111. CrossRefPubMedGoogle Scholar
  114. Karl A, Schaefer M, Malta LS, Dörfel D, Rohleder N, Werner A (2006) A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev 30:1004–1031. CrossRefPubMedGoogle Scholar
  115. Kartalci S, Dogan M, Unal S, Ozcan AC, Ozdemir S, Atmaca M (2011) Pituitary volume in patients with panic disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 35:203–207. CrossRefGoogle Scholar
  116. Kasper S (2006) Anxiety disorders: under-diagnosed and insufficiently treated. Int J Psychiatry Clin Pract 10(Suppl 1):3–9. CrossRefPubMedGoogle Scholar
  117. Kennedy JL, Neves-Pereira M, King N, Lizak MV, Basile VS, Chartier MJ, Stein MB (2001) Dopamine system genes not linked to social phobia. Psychiatr Genet 11:213–217CrossRefPubMedGoogle Scholar
  118. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:617–627. CrossRefPubMedCentralPubMedGoogle Scholar
  119. Kilts CD, Kelsey JE, Knight B, Ely TD, Bowman FD, Gross RE, Selvig A, Gordon A, Newport DJ, Nemeroff CB (2006) The neural correlates of social anxiety disorder and response to pharmacotherapy. Neuropsychopharmacology 31:2243–2253. CrossRefPubMedGoogle Scholar
  120. Kim CH, Cheon KA, Koo MS, Ryu YH, Lee JD, Chang JW, Lee HS (2007) Dopamine transporter density in the basal ganglia in obsessive-compulsive disorder, measured with [123I]IPT SPECT before and after treatment with serotonin reuptake inhibitors. Neuropsychobiology 55:156–162. CrossRefPubMedGoogle Scholar
  121. Kim B, Yoo E, Lee J-Y, Lee KS, Choe AY, Lee JE, Kwack K, Yook K-H, Choi TK, Lee S-H (2013) The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder. J Affect Disord 147:64–71. CrossRefPubMedGoogle Scholar
  122. Kim B, Kim JH, Kim M-K, Lee KS, Kim Y, Choi TK, Kim YT, Lee S-H (2014) Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study. PLoS One 9:e95279. CrossRefPubMedCentralPubMedGoogle Scholar
  123. Kim B, Oh J, Kim M-K, Lee S, Tae WS, Kim CM, Choi TK, Lee S-H (2015) White matter alterations are associated with suicide attempt in patients with panic disorder. J Affect Disord 175:139–146. CrossRefPubMedGoogle Scholar
  124. Kim E, Howes OD, Park JW, Kim SN, Shin SA, Kim BH, Turkheimer FE, Lee YS, Kwon JS (2016) Altered serotonin transporter binding potential in patients with obsessive-compulsive disorder under escitalopram treatment: [11C]DASB PET study. Psychol Med 46:357–366. CrossRefPubMedGoogle Scholar
  125. Kircher T, Arolt V, Jansen A, Pyka M, Reinhardt I, Kellermann T, Konrad C, Lueken U, Gloster AT, Gerlach AL, Ströhle A, Wittmann A, Pfleiderer B, Wittchen H-U, Straube B (2013) Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder. Biol Psychiatry 73:93–101. CrossRefPubMedGoogle Scholar
  126. Klumpp H, Fitzgerald DA, Phan KL (2013) Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder. Prog Neuro-Psychopharmacol Biol Psychiatry 45:83–91. CrossRefGoogle Scholar
  127. Klumpp H, Keutmann MK, Fitzgerald DA, Shankman SA, Phan KL (2014) Resting state amygdala-prefrontal connectivity predicts symptom change after cognitive behavioral therapy in generalized social anxiety disorder. Biol Mood Anxiety Disord 4:14. CrossRefPubMedCentralPubMedGoogle Scholar
  128. Koenen KC, Amstadter AB, Ruggiero KJ, Acierno R, Galea S, Kilpatrick DG, Gelernter J (2009) RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane-exposed adults. Depress Anxiety 26:309–315. CrossRefPubMedCentralPubMedGoogle Scholar
  129. Koenen KC, Duncan LE, Liberzon I, Ressler KJ (2013) From candidate genes to genome-wide association: the challenges and promise of posttraumatic stress disorder genetic studies. Biol Psychiatry 74:634–636. CrossRefPubMedCentralPubMedGoogle Scholar
  130. Konishi J, Asami T, Hayano F, Yoshimi A, Hayasaka S, Fukushima H, Whitford TJ, Inoue T, Hirayasu Y (2014) Multiple white matter volume reductions in patients with panic disorder: relationships between orbitofrontal Gyrus volume and symptom severity and social dysfunction. PLoS One 9:e92862. CrossRefPubMedCentralPubMedGoogle Scholar
  131. Kroes MCW, Whalley MG, Rugg MD, Brewin CR (2011) Association between flashbacks and structural brain abnormalities in posttraumatic stress disorder. Eur Psychiatry 26:525–531. CrossRefPubMedGoogle Scholar
  132. Kuikka JT, Pitkänen A, Lepola U, Partanen K, Vainio P, Bergström KA, Wieler HJ, Kaiser KP, Mittelbach L, Koponen H (1995) Abnormal regional benzodiazepine receptor uptake in the prefrontal cortex in patients with panic disorder. Nucl Med Commun 16:273–280CrossRefPubMedGoogle Scholar
  133. Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs M, Stout JC, Nathan PJ (2010) Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology 35:2403–2413. CrossRefPubMedCentralPubMedGoogle Scholar
  134. Lai C-H, Hsu Y-Y (2011) A subtle grey-matter increase in first-episode, drug-naive major depressive disorder with panic disorder after 6 weeks’ duloxetine therapy. Int J Neuropsychopharmacol 14:225–235. CrossRefPubMedGoogle Scholar
  135. Lai C-H, Wu Y-T (2012a) Fronto-temporo-insula gray matter alterations of first-episode, drug-naïve and very late-onset panic disorder patients. J Affect Disord 140:285–291. CrossRefPubMedGoogle Scholar
  136. Lai C-H, Wu Y-T (2012b) Patterns of fractional amplitude of low-frequency oscillations in occipito-striato-thalamic regions of first-episode drug-naïve panic disorder. J Affect Disord 142:180–185. CrossRefPubMedGoogle Scholar
  137. Lai C-H, Wu Y-T (2013a) Fronto-occipital fasciculus, corpus callosum and superior longitudinal fasciculus tract alterations of first-episode, medication-naïve and late-onset panic disorder patients. J Affect Disord 146:378–382. CrossRefPubMedGoogle Scholar
  138. Lai C-H, Wu Y-T (2013b) Changes in gray matter volume of remitted first-episode, drug-naïve, panic disorder patients after 6-week antidepressant therapy. J Psychiatr Res 47:122–127. CrossRefPubMedGoogle Scholar
  139. Lai C-H, Wu Y-T (2013c) Decreased regional homogeneity in lingual gyrus, increased regional homogeneity in cuneus and correlations with panic symptom severity of first-episode, medication-naïve and late-onset panic disorder patients. Psychiatry Res 211:127–131. CrossRefPubMedGoogle Scholar
  140. Lai C-H, Wu Y-T (2016) The white matter microintegrity alterations of neocortical and limbic association fibers in major depressive disorder and panic disorder: the comparison. Medicine (Baltimore) 95:e2982. CrossRefGoogle Scholar
  141. Lai C-H, Wu Y-T, Yu P-L, Yuan W (2013) Improvements in white matter micro-structural integrity of right uncinate fasciculus and left fronto-occipital fasciculus of remitted first-episode medication-naïve panic disorder patients. J Affect Disord 150:330–336. CrossRefPubMedGoogle Scholar
  142. Lange I, Goossens L, Leibold N, Vervliet B, Sunaert S, Peeters R, van Amelsvoort T, Schruers K (2016) Brain and behavior changes following exposure therapy predict outcome at 8-year follow-up. Psychother Psychosom 85:238–240. CrossRefPubMedCentralPubMedGoogle Scholar
  143. Lanzenberger RR, Mitterhauser M, Spindelegger C, Wadsak W, Klein N, Mien L-K, Holik A, Attarbaschi T, Mossaheb N, Sacher J, Geiss-Granadia T, Kletter K, Kasper S, Tauscher J (2007) Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry 61:1081–1089. CrossRefPubMedGoogle Scholar
  144. Lanzenberger R, Wadsak W, Spindelegger C, Mitterhauser M, Akimova E, Mien L-K, Fink M, Moser U, Savli M, Kranz GS, Hahn A, Kletter K, Kasper S (2010) Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions. Int J Neuropsychopharmacol 13:1129–1143. CrossRefPubMedGoogle Scholar
  145. Lebois LAM, Wolff JD, Ressler KJ (2016) Neuroimaging genetic approaches to Posttraumatic stress disorder. Exp Neurol 284:141–152. CrossRefPubMedCentralPubMedGoogle Scholar
  146. Lee L-T, Tsai HC, Chi MH, Chang WH, Chen KC, Lee IH, Chen PS, Yao WJ, Chiu NT, Yang YK (2015) Lower availability of striatal dopamine transporter in generalized anxiety disorder: a preliminary two-ligand SPECT study. Int Clin Psychopharmacol 30:175–178. CrossRefPubMedGoogle Scholar
  147. Leuchter AF, Cook IA, Hamilton SP, Narr KL, Toga A, Hunter AM, Faull K, Whitelegge J, Andrews AM, Loo J, Way B, Nelson SF, Horvath S, Lebowitz BD (2010) Biomarkers to predict antidepressant response. Curr Psychiatry Rep 12:553–562. CrossRefPubMedCentralPubMedGoogle Scholar
  148. Levy-Gigi E, Szabó C, Kelemen O, Kéri S (2013) Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biol Psychiatry 74:793–800. CrossRefPubMedGoogle Scholar
  149. Li Y, Meng Y, Yuan M, Zhang Y, Ren Z, Zhang Y, Zhu H, Qiu C, Zhang W (2016) Therapy for adult social anxiety disorder: a meta-analysis of functional neuroimaging studies. J Clin Psychiatry 77:e1429–e1438. CrossRefPubMedGoogle Scholar
  150. Liao W, Qiu C, Gentili C, Walter M, Pan Z, Ding J, Zhang W, Gong Q, Chen H (2010) Altered effective connectivity network of the amygdala in social anxiety disorder: a resting-state FMRI study. PLoS One 5:e15238. CrossRefPubMedCentralPubMedGoogle Scholar
  151. Liao M, Yang F, Zhang Y, He Z, Song M, Jiang T, Li Z, Lu S, Wu W, Su L, Li L (2013) Childhood maltreatment is associated with larger left thalamic gray matter volume in adolescents with generalized anxiety disorder. PLoS One 8:e71898. CrossRefPubMedCentralPubMedGoogle Scholar
  152. Liao M, Yang F, Zhang Y, He Z, Su L, Li L (2014) Lack of gender effects on gray matter volumes in adolescent generalized anxiety disorder. J Affect Disord 155:278–282. CrossRefPubMedGoogle Scholar
  153. Liebscher C, Wittmann A, Gechter J, Schlagenhauf F, Lueken U, Plag J, Straube B, Pfleiderer B, Fehm L, Gerlach AL, Kircher T, Fydrich T, Deckert J, Wittchen H-U, Heinz A, Arolt V, Ströhle A (2016) Facing the fear – clinical and neural effects of cognitive behavioural and pharmacotherapy in panic disorder with agoraphobia. Eur Neuropsychopharmacol 26:431–444. CrossRefPubMedGoogle Scholar
  154. Linares IMP, Trzesniak C, Chagas MHN, Hallak JEC, Nardi AE, Crippa JAS (2012) Neuroimaging in specific phobia disorder: a systematic review of the literature. Rev Bras Psiquiatr 34:101–111CrossRefPubMedGoogle Scholar
  155. Lindauer RJL, Booij J, Habraken JBA, van Meijel EPM, Uylings HBM, Olff M, Carlier IVE, den Heeten GJ, van Eck-Smit BLF, Gersons BPR (2008) Effects of psychotherapy on regional cerebral blood flow during trauma imagery in patients with post-traumatic stress disorder: a randomized clinical trial. Psychol Med 38:543–554. CrossRefPubMedGoogle Scholar
  156. Liu W, Yin D, Cheng W, Fan M, You M, Men W, Zang L, Shi D, Zhang F (2015) Abnormal functional connectivity of the amygdala-based network in resting-state FMRI in adolescents with generalized anxiety disorder. Med Sci Monit 21:459–467. CrossRefPubMedCentralPubMedGoogle Scholar
  157. Logue MW, Baldwin C, Guffanti G, Melista E, Wolf EJ, Reardon AF, Uddin M, Wildman D, Galea S, Koenen KC, Miller MW (2013) A genome-wide association study of post-traumatic stress disorder identifies the retinoid-related orphan receptor alpha (RORA) gene as a significant risk locus. Mol Psychiatry 18:937–942. CrossRefGoogle Scholar
  158. Lonsdorf TB, Rück C, Bergström J, Andersson G, Ohman A, Lindefors N, Schalling M (2010) The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder. BMC Psychiatry 10:99. CrossRefPubMedCentralPubMedGoogle Scholar
  159. Lowe SR, Meyers JL, Galea S, Aiello AE, Uddin M, Wildman DE, Koenen KC (2015) RORA and posttraumatic stress trajectories: main effects and interactions with childhood physical abuse history. Brain Behav 5:e00323. CrossRefPubMedCentralPubMedGoogle Scholar
  160. Lueken U, Straube B, Konrad C, Wittchen H-U, Ströhle A, Wittmann A, Pfleiderer B, Uhlmann C, Arolt V, Jansen A, Kircher T (2013) Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia. Am J Psychiatry 170:1345–1355. CrossRefPubMedGoogle Scholar
  161. Lueken U, Straube B, Reinhardt I, Maslowski NI, Wittchen HU, Ströhle A, Wittmann A, Pfleiderer B, Konrad C, Ewert A, Uhlmann C, Arolt V, Jansen A, Kircher T (2014) Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia. Psychol Med 44:381–394. CrossRefPubMedGoogle Scholar
  162. Lueken U, Straube B, Wittchen H-U, Konrad C, Ströhle A, Wittmann A, Pfleiderer B, Arolt V, Kircher T, Deckert J, Reif A (2015) Therapygenetics: anterior cingulate cortex-amygdala coupling is associated with 5-HTTLPR and treatment response in panic disorder with agoraphobia. J Neural Transm 122:135–144. CrossRefGoogle Scholar
  163. MacNamara A, Rabinak CA, Kennedy AE, Fitzgerald DA, Liberzon I, Stein MB, Phan KL (2016) Emotion regulatory brain function and SSRI treatment in PTSD: neural correlates and predictors of change. Neuropsychopharmacology 41:611–618. CrossRefGoogle Scholar
  164. Maddock RJ, Buonocore MH, Kile SJ, Garrett AS (2003) Brain regions showing increased activation by threat-related words in panic disorder. Neuroreport 14:325–328. CrossRefPubMedGoogle Scholar
  165. Makovac E, Meeten F, Watson DR, Garfinkel SN, Critchley HD, Ottaviani C (2016a) Neurostructural abnormalities associated with axes of emotion dysregulation in generalized anxiety. Neuroimage Clin 10:172–181. CrossRefPubMedGoogle Scholar
  166. Makovac E, Meeten F, Watson DR, Herman A, Garfinkel SN, D Critchley H, Ottaviani C (2016b) Alterations in amygdala-prefrontal functional connectivity account for excessive worry and autonomic dysregulation in generalized anxiety disorder. Biol Psychiatry 80:786–795. CrossRefPubMedGoogle Scholar
  167. Malizia AL, Cunningham VJ, Bell CJ, Liddle PF, Jones T, Nutt DJ (1998) Decreased brain GABA(A)-benzodiazepine receptor binding in panic disorder: preliminary results from a quantitative PET study. Arch Gen Psychiatry 55:715–720CrossRefPubMedGoogle Scholar
  168. Månsson KNT, Salami A, Frick A, Carlbring P, Andersson G, Furmark T, Boraxbekk CJ (2016) Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder. Transl Psychiatry 6:e727. CrossRefPubMedCentralPubMedGoogle Scholar
  169. Månsson KNT, Salami A, Carlbring P, Boraxbekk CJ, Andersson G, Furmark T (2017) Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder. Behav Brain Res 318:45–51. CrossRefPubMedGoogle Scholar
  170. Markowitz JS, Weissman MM, Ouellette R, Lish JD, Klerman GL (1989) Quality of life in panic disorder. Arch Gen Psychiatry 46:984–992CrossRefPubMedGoogle Scholar
  171. Maron E, Nutt D (2017) Biological markers of generalized anxiety disorder. Dialogues Clin Neurosci 19:147–158PubMedCentralPubMedGoogle Scholar
  172. Maron E, Kuikka JT, Shlik J, Vasar V, Vanninen E, Tiihonen J (2004a) Reduced brain serotonin transporter binding in patients with panic disorder. Psychiatry Res 132:173–181. CrossRefPubMedGoogle Scholar
  173. Maron E, Kuikka JT, Ulst K, Tiihonen J, Vasar V, Shlik J (2004b) SPECT imaging of serotonin transporter binding in patients with generalized anxiety disorder. Eur Arch Psychiatry Clin Neurosci 254:392–396. CrossRefPubMedGoogle Scholar
  174. Maron E, Hettema JM, Shlik J (2010a) Advances in molecular genetics of panic disorder. Mol Psychiatry 15:681–701. CrossRefPubMedGoogle Scholar
  175. Maron E, Nutt DJ, Kuikka J, Tiihonen J (2010b) Dopamine transporter binding in females with panic disorder may vary with clinical status. J Psychiatr Res 44:56–59. CrossRefPubMedGoogle Scholar
  176. Maron E, Tõru I, Hirvonen J, Tuominen L, Lumme V, Vasar V, Shlik J, Nutt DJ, Helin S, Någren K, Tiihonen J, Hietala J (2011) Gender differences in brain serotonin transporter availability in panic disorder. J Psychopharmacol (Oxf) 25:952–959. CrossRefGoogle Scholar
  177. Maron E, Nutt D, Shlik J (2012) Neuroimaging of serotonin system in anxiety disorders. Curr Pharm Des 18:5699–5708CrossRefPubMedGoogle Scholar
  178. Maslowsky J, Mogg K, Bradley BP, McClure-Tone E, Ernst M, Pine DS, Monk CS (2010) A preliminary investigation of neural correlates of treatment in adolescents with generalized anxiety disorder. J Child Adolesc Psychopharmacol 20:105–111. CrossRefPubMedCentralPubMedGoogle Scholar
  179. Massana G, Serra-Grabulosa JM, Salgado-Pineda P, Gastó C, Junqué C, Massana J, Mercader JM (2003a) Parahippocampal gray matter density in panic disorder: a voxel-based morphometric study. Am J Psychiatry 160:566–568. CrossRefPubMedGoogle Scholar
  180. Massana G, Serra-Grabulosa JM, Salgado-Pineda P, Gastó C, Junqué C, Massana J, Mercader JM, Gómez B, Tobeña A, Salamero M (2003b) Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging. NeuroImage 19:80–90CrossRefPubMedGoogle Scholar
  181. Mataix-Cols D, Wooderson S, Lawrence N, Brammer MJ, Speckens A, Phillips ML (2004) Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder. Arch Gen Psychiatry 61:564–576. CrossRefPubMedGoogle Scholar
  182. Mathew SJ, Mao X, Coplan JD, Smith ELP, Sackeim HA, Gorman JM, Shungu DC (2004) Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. Am J Psychiatry 161:1119–1121. CrossRefPubMedGoogle Scholar
  183. Mathew SJ, Price RB, Mao X, Smith ELP, Coplan JD, Charney DS, Shungu DC (2008) Hippocampal N-acetylaspartate concentration and response to riluzole in generalized anxiety disorder. Biol Psychiatry 63:891–898. CrossRefPubMedGoogle Scholar
  184. Mathew SJ, Price RB, Shungu DC, Mao X, Smith ELP, Amiel JM, Coplan JD (2010) A pilot study of the effects of chronic paroxetine administration on hippocampal N-acetylaspartate in generalized anxiety disorder. J Psychopharmacol (Oxf) 24:1175–1181. CrossRefGoogle Scholar
  185. Mattheisen M, Samuels JF, Wang Y, Greenberg BD, Fyer AJ, McCracken JT, Geller DA, Murphy DL, Knowles JA, Grados MA, Riddle MA, Rasmussen SA, McLaughlin NC, Nurmi EL, Askland KD, Qin HD, Cullen BA, Piacentini J, Pauls DL, Bienvenu OJ, Stewart SE, Liang KY, Goes FS, Maher B, Pulver AE, Shugart YY, Valle D, Lange C, Nestadt G (2015) Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 20:337–344. CrossRefPubMedGoogle Scholar
  186. McClure EB, Adler A, Monk CS, Cameron J, Smith S, Nelson EE, Leibenluft E, Ernst M, Pine DS (2007) fMRI predictors of treatment outcome in pediatric anxiety disorders. Psychopharmacology 191:97–105. CrossRefPubMedGoogle Scholar
  187. Mendlowicz MV, Stein MB (2000) Quality of life in individuals with anxiety disorders. Am J Psychiatry 157:669–682. CrossRefPubMedGoogle Scholar
  188. Meunier D, Ersche KD, Craig KJ, Fornito A, Merlo-Pich E, Fineberg NA, Shabbir SS, Robbins TW, Bullmore ET (2012) Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder. NeuroImage 59:1461–1468. CrossRefPubMedGoogle Scholar
  189. Michelgård A, Appel L, Pissiota A, Frans O, Långström B, Bergström M, Fredrikson M (2007) Symptom provocation in specific phobia affects the substance P neurokinin-1 receptor system. Biol Psychiatry 61:1002–1006. CrossRefPubMedGoogle Scholar
  190. Milham MP, Craddock RC, Klein A (2017) Clinically useful brain imaging for neuropsychiatry: how can we get there? Depress Anxiety 34:578–587. CrossRefPubMedGoogle Scholar
  191. Miner CM, Davidson JR, Potts NL, Tupler LA, Charles HC, Krishnan KR (1995) Brain fluoxetine measurements using fluorine magnetic resonance spectroscopy in patients with social phobia. Biol Psychiatry 38:696–698. CrossRefPubMedGoogle Scholar
  192. Molina E, Cervilla J, Rivera M, Torres F, Bellón JA, Moreno B, King M, Nazareth I, Gutiérrez B (2011) Polymorphic variation at the serotonin 1-A receptor gene is associated with comorbid depression and generalized anxiety. Psychiatr Genet 21:195–201. CrossRefPubMedGoogle Scholar
  193. Monk CS, Nelson EE, McClure EB, Mogg K, Bradley BP, Leibenluft E, Blair RJR, Chen G, Charney DS, Ernst M, Pine DS (2006) Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder. Am J Psychiatry 163:1091–1097. CrossRefPubMedGoogle Scholar
  194. Monk CS, Telzer EH, Mogg K, Bradley BP, Mai X, Louro HMC, Chen G, McClure-Tone EB, Ernst M, Pine DS (2008) Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 65:568–576. CrossRefPubMedCentralPubMedGoogle Scholar
  195. Moon C-M, Jeong G-W (2015) Alterations in white matter volume and its correlation with clinical characteristics in patients with generalized anxiety disorder. Neuroradiology 57:1127–1134. CrossRefPubMedGoogle Scholar
  196. Moon C-M, Jeong G-W (2017) Abnormalities in gray and white matter volumes associated with explicit memory dysfunction in patients with generalized anxiety disorder. Acta Radiol 58:353–361. CrossRefPubMedGoogle Scholar
  197. Moon C-M, Kang H-K, Jeong G-W (2015a) Metabolic change in the right dorsolateral prefrontal cortex and its correlation with symptom severity in patients with generalized anxiety disorder: proton magnetic resonance spectroscopy at 3 Tesla. Psychiatry Clin Neurosci 69:422–430. CrossRefPubMedGoogle Scholar
  198. Moon C-M, Yang J-C, Jeong G-W (2015b) Explicit verbal memory impairments associated with brain functional deficits and morphological alterations in patients with generalized anxiety disorder. J Affect Disord 186:328–336. CrossRefPubMedGoogle Scholar
  199. Moreira FP, Fabião JD, Bittencourt G, Wiener CD, Jansen K, Oses JP, Quevedo L de Á, Souza LDM, Crispim D, Portela LV, Pinheiro RT, Lara DR, Kaster MP, da Silva RA, Ghisleni G (2015) The met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder. Psychiatr Genet 25:201–207. CrossRefPubMedGoogle Scholar
  200. Morey RA, Gold AL, LaBar KS, Beall SK, Brown VM, Haswell CC, Nasser JD, Wagner HR, McCarthy G, Mid-Atlantic MIRECC Workgroup (2012) Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatry 69:1169–1178. CrossRefPubMedCentralPubMedGoogle Scholar
  201. Morgiève M, N’Diaye K, Haynes WIA, Granger B, Clair AH, Pelissolo A, Mallet L (2014) Dynamics of psychotherapy-related cerebral haemodynamic changes in obsessive compulsive disorder using a personalized exposure task in functional magnetic resonance imaging. Psychol Med 44:1461–1473. CrossRefPubMedGoogle Scholar
  202. Mountz JM, Modell JG, Wilson MW, Curtis GC, Lee MA, Schmaltz S, Kuhl DE (1989) Positron emission tomographic evaluation of cerebral blood flow during state anxiety in simple phobia. Arch Gen Psychiatry 46:501–504. CrossRefPubMedGoogle Scholar
  203. Murrough JW, Czermak C, Henry S, Nabulsi N, Gallezot J-D, Gueorguieva R, Planeta-Wilson B, Krystal JH, Neumaier JF, Huang Y, Ding Y-S, Carson RE, Neumeister A (2011a) The effect of early trauma exposure on serotonin type 1B receptor expression revealed by reduced selective radioligand binding. Arch Gen Psychiatry 68:892–900. CrossRefPubMedCentralPubMedGoogle Scholar
  204. Murrough JW, Huang Y, Hu J, Henry S, Williams W, Gallezot J-D, Bailey CR, Krystal JH, Carson RE, Neumeister A (2011b) Reduced amygdala serotonin transporter binding in posttraumatic stress disorder. Biol Psychiatry 70:1033–1038. CrossRefPubMedCentralPubMedGoogle Scholar
  205. Mushtaq D, Ali A, Margoob MA, Murtaza I, Andrade C (2012) Association between serotonin transporter gene promoter-region polymorphism and 4- and 12-week treatment response to sertraline in posttraumatic stress disorder. J Affect Disord 136:955–962. CrossRefPubMedGoogle Scholar
  206. Myers JFM, Evans CJ, Kalk NJ, Edden RAE, Lingford-Hughes AR (2014) Measurement of GABA using J-difference edited 1H-MRS following modulation of synaptic GABA concentration with tiagabine. Synapse 68:355–362. CrossRefPubMedGoogle Scholar
  207. Na K-S, Ham B-J, Lee M-S, Kim L, Kim Y-K, Lee H-J, Yoon H-K (2013) Decreased gray matter volume of the medial orbitofrontal cortex in panic disorder with agoraphobia: a preliminary study. Prog Neuro-Psychopharmacol Biol Psychiatry 45:195–200. CrossRefGoogle Scholar
  208. Nakao T, Sanematsu H, Yoshiura T, Togao O, Murayama K, Tomita M, Masuda Y, Kanba S (2011) fMRI of patients with social anxiety disorder during a social situation task. Neurosci Res 69:67–72. CrossRefPubMedGoogle Scholar
  209. Nash JR, Sargent PA, Rabiner EA, Hood SD, Argyropoulos SV, Potokar JP, Grasby PM, Nutt DJ (2008) Serotonin 5-HT1A receptor binding in people with panic disorder: positron emission tomography study. Br J Psychiatry 193:229–234. CrossRefPubMedGoogle Scholar
  210. Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA, Eckelman W, Herscovitch P, Charney DS, Drevets WC (2004) Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci 24:589–591. CrossRefPubMedGoogle Scholar
  211. Nievergelt CM, Maihofer AX, Mustapic M, Yurgil KA, Schork NJ, Miller MW, Logue MW, Geyer MA, Risbrough VB, O’Connor DT, Baker DG (2015) Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: a genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene. Psychoneuroendocrinology 51:459–471. CrossRefPubMedGoogle Scholar
  212. Nitschke JB, Sarinopoulos I, Oathes DJ, Johnstone T, Whalen PJ, Davidson RJ, Kalin NH (2009) Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. Am J Psychiatry 166:302–310. CrossRefPubMedCentralPubMedGoogle Scholar
  213. Noyes R, Crowe RR, Harris EL, Hamra BJ, McChesney CM, Chaudhry DR (1986) Relationship between panic disorder and agoraphobia. A family study. Arch Gen Psychiatry 43:227–232CrossRefPubMedGoogle Scholar
  214. Nutt DJ, Bell CJ, Malizia AL (1998) Brain mechanisms of social anxiety disorder. J Clin Psychiatry 59(Suppl 17):4–11PubMedGoogle Scholar
  215. Olesen J, Gustavsson A, Svensson M, Wittchen HU, Jönsson B, CDBE2010 Study Group, European Brain Council (2012) The economic cost of brain disorders in Europe. Eur J Neurol 19:155–162. CrossRefPubMedGoogle Scholar
  216. Olver JS, O’Keefe G, Jones GR, Burrows GD, Tochon-Danguy HJ, Ackermann U, Scott A, Norman TR (2009) Dopamine D1 receptor binding in the striatum of patients with obsessive-compulsive disorder. J Affect Disord 114:321–326. CrossRefPubMedGoogle Scholar
  217. Olver JS, O’Keefe G, Jones GR, Burrows GD, Tochon-Danguy HJ, Ackermann U, Scott AM, Norman TR (2010) Dopamine D(1) receptor binding in the anterior cingulate cortex of patients with obsessive-compulsive disorder. Psychiatry Res 183:85–88. CrossRefPubMedGoogle Scholar
  218. Ortiz AE, Ortiz AG, Falcon C, Morer A, Plana MT, Bargalló N, Lázaro L (2015) 1H-MRS of the anterior cingulate cortex in childhood and adolescent obsessive-compulsive disorder: a case-control study. Eur Neuropsychopharmacol 25:60–68. CrossRefPubMedGoogle Scholar
  219. Ottaviani C, Cevolani D, Nucifora V, Borlimi R, Agati R, Leonardi M, De Plato G, Brighetti G (2012) Amygdala responses to masked and low spatial frequency fearful faces: a preliminary fMRI study in panic disorder. Psychiatry Res 203:159–165. CrossRefPubMedGoogle Scholar
  220. Palm ME, Elliott R, McKie S, Deakin JFW, Anderson IM (2011) Attenuated responses to emotional expressions in women with generalized anxiety disorder. Psychol Med 41:1009–1018. CrossRefPubMedGoogle Scholar
  221. Pannekoek JN, Veer IM, van Tol M-J, van der Werff SJA, Demenescu LR, Aleman A, Veltman DJ, Zitman FG, Rombouts SARB, van der Wee NJA (2013) Aberrant limbic and salience network resting-state functional connectivity in panic disorder without comorbidity. J Affect Disord 145:29–35. CrossRefPubMedGoogle Scholar
  222. Pantazatos SP, Talati A, Schneier FR, Hirsch J (2014) Reduced anterior temporal and hippocampal functional connectivity during face processing discriminates individuals with social anxiety disorder from healthy controls and panic disorder, and increases following treatment. Neuropsychopharmacology 39:425–434. CrossRefPubMedGoogle Scholar
  223. Paquette V, Lévesque J, Mensour B, Leroux J-M, Beaudoin G, Bourgouin P, Beauregard M (2003) “Change the mind and you change the brain”: effects of cognitive-behavioral therapy on the neural correlates of spider phobia. NeuroImage 18:401–409. CrossRefPubMedGoogle Scholar
  224. Paulesu E, Sambugaro E, Torti T, Danelli L, Ferri F, Scialfa G, Sberna M, Ruggiero GM, Bottini G, Sassaroli S (2010) Neural correlates of worry in generalized anxiety disorder and in normal controls: a functional MRI study. Psychol Med 40:117–124. CrossRefPubMedGoogle Scholar
  225. Perani D, Garibotto V, Gorini A, Moresco RM, Henin M, Panzacchi A, Matarrese M, Carpinelli A, Bellodi L, Fazio F (2008) In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder. NeuroImage 42:306–314. CrossRefPubMedGoogle Scholar
  226. Perna G, Favaron E, Di Bella D, Bussi R, Bellodi L (2005) Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene. Neuropsychopharmacology 30:2230–2235. CrossRefPubMedGoogle Scholar
  227. Petrowski K, Wintermann G, Smolka MN, Huebner T, Donix M (2014) The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia. J Affect Disord 152–154:454–461. CrossRefPubMedGoogle Scholar
  228. Phan KL, Fitzgerald DA, Cortese BM, Seraji-Bozorgzad N, Tancer ME, Moore GJ (2005) Anterior cingulate neurochemistry in social anxiety disorder: 1H-MRS at 4 Tesla. Neuroreport 16:183–186CrossRefPubMedGoogle Scholar
  229. Pietrzak RH, Sumner JA, Aiello AE, Uddin M, Neumeister A, Guffanti G, Koenen KC (2015) Association of the rs2242446 polymorphism in the norepinephrine transporter gene SLC6A2 and anxious arousal symptoms of posttraumatic stress disorder. J Clin Psychiatry 76:e537–e538. CrossRefPubMedCentralPubMedGoogle Scholar
  230. Pillay SS, Gruber SA, Rogowska J, Simpson N, Yurgelun-Todd DA (2006) fMRI of fearful facial affect recognition in panic disorder: the cingulate gyrus-amygdala connection. J Affect Disord 94:173–181. CrossRefPubMedGoogle Scholar
  231. Pillay SS, Rogowska J, Gruber SA, Simpson N, Yurgelun-Todd DA (2007) Recognition of happy facial affect in panic disorder: an fMRI study. J Anxiety Disord 21:381–393. CrossRefPubMedGoogle Scholar
  232. Piras F, Piras F, Chiapponi C, Girardi P, Caltagirone C, Spalletta G (2015) Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies. Cortex 62:89–108. CrossRefPubMedGoogle Scholar
  233. Pissiota A, Frans O, Michelgård A, Appel L, Långström B, Flaten MA, Fredrikson M (2003) Amygdala and anterior cingulate cortex activation during affective startle modulation: a PET study of fear. Eur J Neurosci 18:1325–1331CrossRefPubMedGoogle Scholar
  234. Poletti S, Radaelli D, Cucchi M, Ricci L, Vai B, Smeraldi E, Benedetti F (2015) Neural correlates of anxiety sensitivity in panic disorder: a functional magnetic resonance imaging study. Psychiatry Res 233:95–101. CrossRefPubMedGoogle Scholar
  235. Pollack MH, Jensen JE, Simon NM, Kaufman RE, Renshaw PF (2008) High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam. Prog Neuro-Psychopharmacol Biol Psychiatry 32:739–743. CrossRefGoogle Scholar
  236. Posner J, Marsh R, Maia TV, Peterson BS, Gruber A, Simpson HB (2014) Reduced functional connectivity within the limbic cortico-striato-thalamo-cortical loop in unmedicated adults with obsessive-compulsive disorder. Hum Brain Mapp 35:2852–2860. CrossRefPubMedGoogle Scholar
  237. Prasko J, Horácek J, Záleský R, Kopecek M, Novák T, Pasková B, Skrdlantová L, Belohlávek O, Höschl C (2004) The change of regional brain metabolism (18FDG PET) in panic disorder during the treatment with cognitive behavioral therapy or antidepressants. Neuro Endocrinol Lett 25:340–348PubMedGoogle Scholar
  238. Protopopescu X, Pan H, Tuescher O, Cloitre M, Goldstein M, Engelien A, Yang Y, Gorman J, LeDoux J, Stern E, Silbersweig D (2006) Increased brainstem volume in panic disorder: a voxel-based morphometric study. Neuroreport 17:361–363. CrossRefPubMedGoogle Scholar
  239. Qin H, Samuels JF, Wang Y, Zhu Y, Grados MA, Riddle MA, Greenberg BD, Knowles JA, Fyer AJ, McCracken JT, Murphy DL, Rasmussen SA, Cullen BA, Piacentini J, Geller D, Stewart SE, Pauls D, Bienvenu OJ, Goes FS, Maher B, Pulver AE, Valle D, Lange C, Mattheisen M, McLaughlin NC, Liang KY, Nurmi EL, Askland KD, Nestadt G, Shugart YY (2016) Whole-genome association analysis of treatment response in obsessive-compulsive disorder. Mol Psychiatry 21:270–276. CrossRefPubMedGoogle Scholar
  240. Qiu L, Fu X, Wang S, Tang Q, Chen X, Cheng L, Zhang F, Zhou Z, Tian L (2017) Abnormal regional spontaneous neuronal activity associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder revealed by resting-state functional MRI. Neurosci Lett 640:99–104. CrossRefPubMedGoogle Scholar
  241. Radua J, van den Heuvel OA, Surguladze S, Mataix-Cols D (2010) Meta-analytical comparison of voxel-based morphometry studies in obsessive-compulsive disorder vs other anxiety disorders. Arch Gen Psychiatry 67:701–711. CrossRefPubMedGoogle Scholar
  242. Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR, Fischman AJ (1994) Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry 51:62–70CrossRefPubMedGoogle Scholar
  243. Rauch SL, Savage CR, Alpert NM, Miguel EC, Baer L, Breiter HC, Fischman AJ, Manzo PA, Moretti C, Jenike MA (1995) A positron emission tomographic study of simple phobic symptom provocation. Arch Gen Psychiatry 52:20–28CrossRefPubMedGoogle Scholar
  244. Rauch SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA (2002) Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study. Neuropsychopharmacology 27:782–791. CrossRefPubMedGoogle Scholar
  245. Rauch SL, Wright CI, Martis B, Busa E, McMullin KG, Shin LM, Dale AM, Fischl B (2004) A magnetic resonance imaging study of cortical thickness in animal phobia. Biol Psychiatry 55:946–952. CrossRefPubMedGoogle Scholar
  246. Ravindran LN, Stein MB (2010) The pharmacologic treatment of anxiety disorders: a review of progress. J Clin Psychiatry 71:839–854. CrossRefPubMedGoogle Scholar
  247. Reif A, Richter J, Straube B, Höfler M, Lueken U, Gloster AT, Weber H, Domschke K, Fehm L, Ströhle A, Jansen A, Gerlach A, Pyka M, Reinhardt I, Konrad C, Wittmann A, Pfleiderer B, Alpers GW, Pauli P, Lang T, Arolt V, Wittchen HU, Hamm A, Kircher T, Deckert J (2014) MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy. Mol Psychiatry 19:122–128. CrossRefPubMedGoogle Scholar
  248. Reinecke A, Thilo K, Filippini N, Croft A, Harmer CJ (2014) Predicting rapid response to cognitive-behavioural treatment for panic disorder: the role of hippocampus, insula, and dorsolateral prefrontal cortex. Behav Res Ther 62:120–128. CrossRefPubMedGoogle Scholar
  249. Rice DP, Miller LS (1998) Health economics and cost implications of anxiety and other mental disorders in the United States. Br J Psychiatry Suppl 34:4–9CrossRefGoogle Scholar
  250. Riedel O, Klotsche J, Spottke A, Deuschl G, Förstl H, Henn F, Heuser I, Oertel W, Reichmann H, Riederer P, Trenkwalder C, Dodel R, Wittchen H-U (2010) Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449 outpatients with Parkinson’s disease. J Neurol 257:1073–1082. CrossRefPubMedGoogle Scholar
  251. Roppongi T, Nakamura M, Asami T, Hayano F, Otsuka T, Uehara K, Fujiwara A, Saeki T, Hayasaka S, Yoshida T, Shimizu R, Inoue T, Hirayasu Y (2010) Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder. Psychiatry Clin Neurosci 64:318–326. CrossRefPubMedGoogle Scholar
  252. Rosso IM, Makris N, Britton JC, Price LM, Gold AL, Zai D, Bruyere J, Deckersbach T, Killgore WDS, Rauch SL (2010) Anxiety sensitivity correlates with two indices of right anterior insula structure in specific animal phobia. Depress Anxiety 27:1104–1110. CrossRefPubMedCentralPubMedGoogle Scholar
  253. Rosso IM, Olson EA, Britton JC, Stewart SE, Papadimitriou G, Killgore WD, Makris N, Wilhelm S, Jenike MA, Rauch SL (2014) Brain white matter integrity and association with age at onset in pediatric obsessive-compulsive disorder. Biol Mood Anxiety Disord 4:13. CrossRefPubMedCentralPubMedGoogle Scholar
  254. Rosso IM, Crowley DJ, Silveri MM, Rauch SL, Jensen JE (2017) Hippocampus glutamate and N-acetyl aspartate markers of excitotoxic neuronal compromise in posttraumatic stress disorder. Neuropsychopharmacology 42:1698–1705. CrossRefPubMedCentralPubMedGoogle Scholar
  255. Rotge J-Y, Langbour N, Guehl D, Bioulac B, Jaafari N, Allard M, Aouizerate B, Burbaud P (2010) Gray matter alterations in obsessive-compulsive disorder: an anatomic likelihood estimation meta-analysis. Neuropsychopharmacology 35:686–691. CrossRefPubMedGoogle Scholar
  256. Roy AK, Fudge JL, Kelly C, Perry JSA, Daniele T, Carlisi C, Benson B, Castellanos FX, Milham MP, Pine DS, Ernst M (2013) Intrinsic functional connectivity of amygdala-based networks in adolescent generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry 52:290–299.e2. CrossRefPubMedCentralPubMedGoogle Scholar
  257. Samochowiec J, Hajduk A, Samochowiec A, Horodnicki J, Stepień G, Grzywacz A, Kucharska-Mazur J (2004) Association studies of MAO-A, COMT, and 5-HTT genes polymorphisms in patients with anxiety disorders of the phobic spectrum. Psychiatry Res 128:21–26. CrossRefPubMedGoogle Scholar
  258. Sanematsu H, Nakao T, Yoshiura T, Nabeyama M, Togao O, Tomita M, Masuda Y, Nakatani E, Nakagawa A, Kanba S (2010) Predictors of treatment response to fluvoxamine in obsessive-compulsive disorder: an fMRI study. J Psychiatr Res 44:193–200. CrossRefPubMedGoogle Scholar
  259. Saxena S, Brody AL, Maidment KM, Dunkin JJ, Colgan M, Alborzian S, Phelps ME, Baxter LR (1999) Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder. Neuropsychopharmacology 21:683–693. CrossRefPubMedGoogle Scholar
  260. Schienle A, Schäfer A, Hermann A, Rohrmann S, Vaitl D (2007) Symptom provocation and reduction in patients suffering from spider phobia: an fMRI study on exposure therapy. Eur Arch Psychiatry Clin Neurosci 257:486–493. CrossRefPubMedGoogle Scholar
  261. Schienle A, Schäfer A, Stark R, Vaitl D (2009) Long-term effects of cognitive behavior therapy on brain activation in spider phobia. Psychiatry Res 172:99–102. CrossRefPubMedGoogle Scholar
  262. Schlund MW, Verduzco G, Cataldo MF, Hoehn-Saric R (2012) Generalized anxiety modulates frontal and limbic activation in major depression. Behav Brain Funct 8:8. CrossRefPubMedCentralPubMedGoogle Scholar
  263. Schneier FR, Liebowitz MR, Abi-Dargham A, Zea-Ponce Y, Lin SH, Laruelle M (2000) Low dopamine D(2) receptor binding potential in social phobia. Am J Psychiatry 157:457–459. CrossRefPubMedGoogle Scholar
  264. Schneier FR, Abi-Dargham A, Martinez D, Slifstein M, Hwang D-R, Liebowitz MR, Laruelle M (2009) Dopamine transporters, D2 receptors, and dopamine release in generalized social anxiety disorder. Depress Anxiety 26:411–418. CrossRefPubMedCentralPubMedGoogle Scholar
  265. Schür RR, Draisma LWR, Wijnen JP, Boks MP, Koevoets MGJC, Joëls M, Klomp DW, Kahn RS, Vinkers CH (2016) Brain GABA levels across psychiatric disorders: a systematic literature review and meta-analysis of (1) H-MRS studies. Hum Brain Mapp 37:3337–3352. CrossRefPubMedGoogle Scholar
  266. Schwartz CE, Kunwar PS, Hirshfeld-Becker DR, Henin A, Vangel MG, Rauch SL, Biederman J, Rosenbaum JF (2015) Behavioral inhibition in childhood predicts smaller hippocampal volume in adolescent offspring of parents with panic disorder. Transl Psychiatry 5:e605. CrossRefPubMedCentralPubMedGoogle Scholar
  267. Scott KA, Hoban AE, Clarke G, Moloney GM, Dinan TG, Cryan JF (2015) Thinking small: towards microRNA-based therapeutics for anxiety disorders. Expert Opin Investig Drugs 24:529–542. CrossRefPubMedGoogle Scholar
  268. Seedat S, Warwick J, van Heerden B, Hugo C, Zungu-Dirwayi N, Van Kradenburg J, Stein DJ (2004) Single photon emission computed tomography in posttraumatic stress disorder before and after treatment with a selective serotonin reuptake inhibitor. J Affect Disord 80:45–53. CrossRefPubMedGoogle Scholar
  269. Seo H-J, Choi YH, Chung Y-A, Rho W, Chae J-H (2014) Changes in cerebral blood flow after cognitive behavior therapy in patients with panic disorder: a SPECT study. Neuropsychiatr Dis Treat 10:661–669. CrossRefPubMedCentralPubMedGoogle Scholar
  270. Shaw P, Sharp W, Sudre G, Wharton A, Greenstein D, Raznahan A, Evans A, Chakravarty MM, Lerch JP, Rapoport J (2015) Subcortical and cortical morphological anomalies as an endophenotype in obsessive-compulsive disorder. Mol Psychiatry 20:224–231. CrossRefPubMedGoogle Scholar
  271. Shin D-J, Jung WH, He Y, Wang J, Shim G, Byun MS, Jang JH, Kim SN, Lee TY, Park HY, Kwon JS (2014) The effects of pharmacological treatment on functional brain connectome in obsessive-compulsive disorder. Biol Psychiatry 75:606–614. CrossRefPubMedGoogle Scholar
  272. Shinoura N, Yamada R, Tabei Y, Otani R, Itoi C, Saito S, Midorikawa A (2011) Damage to the right dorsal anterior cingulate cortex induces panic disorder. J Affect Disord 133:569–572. CrossRefPubMedGoogle Scholar
  273. Simpson HB, Slifstein M, Bender J, Xu X, Hackett E, Maher MJ, Abi-Dargham A (2011) Serotonin 2A receptors in obsessive-compulsive disorder: a positron emission tomography study with [11C]MDL 100907. Biol Psychiatry 70:897–904. CrossRefPubMedCentralPubMedGoogle Scholar
  274. Sladky R, Höflich A, Atanelov J, Kraus C, Baldinger P, Moser E, Lanzenberger R, Windischberger C (2012) Increased neural habituation in the amygdala and orbitofrontal cortex in social anxiety disorder revealed by FMRI. PLoS One 7:e50050. CrossRefPubMedCentralPubMedGoogle Scholar
  275. Sladky R, Höflich A, Küblböck M, Kraus C, Baldinger P, Moser E, Lanzenberger R, Windischberger C (2015) Disrupted effective connectivity between the amygdala and orbitofrontal cortex in social anxiety disorder during emotion discrimination revealed by dynamic causal modeling for FMRI. Cereb Cortex 25:895–903. CrossRefPubMedGoogle Scholar
  276. Smith AK, Conneely KN, Kilaru V, Mercer KB, Weiss TE, Bradley B, Tang Y, Gillespie CF, Cubells JF, Ressler KJ (2011) Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder. Am J Med Genet B Neuropsychiatr Genet 156B:700–708. CrossRefPubMedCentralPubMedGoogle Scholar
  277. Sobanski T, Wagner G, Peikert G, Gruhn U, Schluttig K, Sauer H, Schlösser R (2010) Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study. Psychol Med 40:1879–1886. CrossRefPubMedGoogle Scholar
  278. Steiger VR, Brühl AB, Weidt S, Delsignore A, Rufer M, Jäncke L, Herwig U, Hänggi J (2017) Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: a longitudinal multimodal MRI study. Mol Psychiatry 22:1164–1171. CrossRefGoogle Scholar
  279. Stein MB, Leslie WD (1996) A brain single photon-emission computed tomography (SPECT) study of generalized social phobia. Biol Psychiatry 39:825–828. CrossRefPubMedGoogle Scholar
  280. Stein MB, Seedat S, Gelernter J (2006) Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psychopharmacology 187:68–72. CrossRefGoogle Scholar
  281. Stein MB, Keshaviah A, Haddad SA, Van Ameringen M, Simon NM, Pollack MH, Smoller JW (2014) Influence of RGS2 on sertraline treatment for social anxiety disorder. Neuropsychopharmacology 39:1340–1346. CrossRefPubMedCentralPubMedGoogle Scholar
  282. Stein MB, Chen C-Y, Ursano RJ, Cai T, Gelernter J, Heeringa SG, Jain S, Jensen KP, Maihofer AX, Mitchell C, Nievergelt CM, Nock MK, Neale BM, Polimanti R, Ripke S, Sun X, Thomas ML, Wang Q, Ware EB, Borja S, Kessler RC, Smoller JW, Army Study to Assess Risk and Resilience in Servicemembers (STARRS) Collaborators (2016) Genome-wide association studies of posttraumatic stress disorder in 2 cohorts of US Army Soldiers. JAMA Psychiat 73:695–704. CrossRefGoogle Scholar
  283. Stengler-Wenzke K, Müller U, Barthel H, Angermeyer MC, Sabri O, Hesse S (2006) Serotonin transporter imaging with [123I]beta-CIT SPECT before and after one year of citalopram treatment of obsessive-compulsive disorder. Neuropsychobiology 53:40–45. CrossRefPubMedGoogle Scholar
  284. Stewart SE, Mayerfeld C, Arnold PD, Crane JR, O’Dushlaine C, Fagerness JA, Yu D, Scharf JM, Chan E, Kassam F, Moya PR, Wendland JR, Delorme R, Richter MA, Kennedy JL, Veenstra-VanderWeele J, Samuels J, Greenberg BD, McCracken JT, Knowles JA, Fyer AJ, Rauch SL, Riddle MA, Grados MA, Bienvenu OJ, Cullen B, Wang Y, Shugart YY, Piacentini J, Rasmussen S, Nestadt G, Murphy DL, Jenike MA, Cook EH, Pauls DL, Hanna GL, Mathews CA (2013a) Meta-analysis of association between obsessive-compulsive disorder and the 3′ region of neuronal glutamate transporter gene SLC1A1. Am J Med Genet B Neuropsychiatr Genet 162B:367–379. CrossRefGoogle Scholar
  285. Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, Arnold PD, Evans PD, Gamazon ER, Davis LK, Osiecki L, McGrath L, Haddad S, Crane J, Hezel D, Illman C, Mayerfeld C, Konkashbaev A, Liu C, Pluzhnikov A, Tikhomirov A, Edlund CK, Rauch SL, Moessner R, Falkai P, Maier W, Ruhrmann S, Grabe HJ, Lennertz L, Wagner M, Bellodi L, Cavallini MC, Richter MA, Cook EH, Kennedy JL, Rosenberg D, Stein DJ, Hemmings SMJ, Lochner C, Azzam A, Chavira DA, Fournier E, Garrido H, Sheppard B, Umaña P, Murphy DL, Wendland JR, Veenstra-Vander Weele J, Denys D, Blom R, Deforce D, Van Nieuwerburgh F, Westenberg HGM, Walitza S, Egberts K, Renner T, Miguel EC, Cappi C, Hounie AG, Conceição do Rosário M, Sampaio AS, Vallada H, Nicolini H, Lanzagorta N, Camarena B, Delorme R, Leboyer M, Pato CN, Pato MT, Voyiaziakis E, Heutink P, Cath DC, Posthuma D, Smit JH, Samuels J, Bienvenu OJ, Cullen B, Fyer AJ, Grados MA, Greenberg BD, McCracken JT, Riddle MA, Wang Y, Coric V, Leckman JF, Bloch M, Pittenger C, Eapen V, Black DW, Ophoff RA, Strengman E, Cusi D, Turiel M, Frau F, Macciardi F, Gibbs JR, Cookson MR, Singleton A, North American Brain Expression Consortium, Hardy J, UK Brain Expression Database, Crenshaw AT, Parkin MA, Mirel DB, Conti DV, Purcell S, Nestadt G, Hanna GL, Jenike MA, Knowles JA, Cox N, Pauls DL (2013b) Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry 18:788–798. CrossRefPubMedGoogle Scholar
  286. Strawn JR, Bitter SM, Weber WA, Chu W-J, Whitsel RM, Adler C, Cerullo MA, Eliassen J, Strakowski SM, DelBello MP (2012) Neurocircuitry of generalized anxiety disorder in adolescents: a pilot functional neuroimaging and functional connectivity study. Depress Anxiety 29:939–947. CrossRefPubMedGoogle Scholar
  287. Strawn JR, Wehry AM, Chu W-J, Adler CM, Eliassen JC, Cerullo MA, Strakowski SM, Delbello MP (2013) Neuroanatomic abnormalities in adolescents with generalized anxiety disorder: a voxel-based morphometry study. Depress Anxiety 30:842–848. CrossRefPubMedGoogle Scholar
  288. Strawn JR, John Wegman C, Dominick KC, Swartz MS, Wehry AM, Patino LR, Strakowski SM, Adler CM, Eliassen JC, DelBello MP (2014) Cortical surface anatomy in pediatric patients with generalized anxiety disorder. J Anxiety Disord 28:717–723. CrossRefPubMedGoogle Scholar
  289. Sullivan GM, Ogden RT, Huang Y-Y, Oquendo MA, Mann JJ, Parsey RV (2013) Higher in vivo serotonin-1a binding in posttraumatic stress disorder: a PET study with [11C]WAY-100635. Depress Anxiety 30:197–206. CrossRefPubMedGoogle Scholar
  290. Swedo SE (2002) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Mol Psychiatry 7(Suppl 2):S24–S25. CrossRefPubMedGoogle Scholar
  291. Tadic A, Rujescu D, Szegedi A, Giegling I, Singer P, Möller HJ, Dahmen N (2003) Association of a MAOA gene variant with generalized anxiety disorder, but not with panic disorder or major depression. Am J Med Genet B Neuropsychiatr Genet 117B:1–6. CrossRefPubMedGoogle Scholar
  292. Tan L, Fan Q, You C, Wang J, Dong Z, Wang X, Chen K, Xiao Z, Jiang K (2013) Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study. Neurosci Bull 29:642–648. CrossRefPubMedCentralPubMedGoogle Scholar
  293. Tang W, Zhu Q, Gong X, Zhu C, Wang Y, Chen S (2016) Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: a voxel-based morphometric and fMRI study of the whole brain. Behav Brain Res 313:17–22. CrossRefPubMedGoogle Scholar
  294. Taylor S (2013) Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry 18:799–805. CrossRefPubMedGoogle Scholar
  295. Tiihonen J, Kuikka J, Bergström K, Lepola U, Koponen H, Leinonen E (1997a) Dopamine reuptake site densities in patients with social phobia. Am J Psychiatry 154:239–242. CrossRefPubMedGoogle Scholar
  296. Tiihonen J, Kuikka J, Räsänen P, Lepola U, Koponen H, Liuska A, Lehmusvaara A, Vainio P, Könönen M, Bergström K, Yu M, Kinnunen I, Akerman K, Karhu J (1997b) Cerebral benzodiazepine receptor binding and distribution in generalized anxiety disorder: a fractal analysis. Mol Psychiatry 2:463–471CrossRefPubMedGoogle Scholar
  297. Tillfors M, Furmark T, Marteinsdottir I, Fischer H, Pissiota A, Långström B, Fredrikson M (2001) Cerebral blood flow in subjects with social phobia during stressful speaking tasks: a PET study. Am J Psychiatry 158:1220–1226. CrossRefPubMedGoogle Scholar
  298. Tillfors M, Furmark T, Marteinsdottir I, Fredrikson M (2002) Cerebral blood flow during anticipation of public speaking in social phobia: a PET study. Biol Psychiatry 52:1113–1119CrossRefPubMedGoogle Scholar
  299. Trautmann S, Richter J, Muehlhan M, Höfler M, Wittchen H-U, Domschke K, Ströhle A, Hamm AO, Weber H, Kircher T, Arolt V, Gerlach AL, Alpers GW, Fydrich T, Lang T, Reif A (2017) Does prior traumatization affect the treatment outcome of CBT for panic disorder? The potential role of the MAOA gene and depression symptoms. Eur Arch Psychiatry Clin Neurosci.
  300. Tromp DPM, Grupe DW, Oathes DJ, McFarlin DR, Hernandez PJ, Kral TRA, Lee JE, Adams M, Alexander AL, Nitschke JB (2012) Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Arch Gen Psychiatry 69:925–934. CrossRefPubMedCentralPubMedGoogle Scholar
  301. Tükel R, Aydın K, Ertekin E, Özyıldırım SŞ, Barburoğlu M (2015) 1H-magnetic resonance spectroscopy in obsessive-compulsive disorder: effects of 12 weeks of sertraline treatment on brain metabolites. Eur Arch Psychiatry Clin Neurosci 265:219–226. CrossRefPubMedGoogle Scholar
  302. Tükel R, Aydın K, Yüksel Ç, Ertekin E, Koyuncu A (2016) Proton magnetic resonance spectroscopy in social anxiety disorder. J Neuropsychiatry Clin Neurosci 28:138–142. CrossRefPubMedGoogle Scholar
  303. Tupler LA, Davidson JR, Smith RD, Lazeyras F, Charles HC, Krishnan KR (1997) A repeat proton magnetic resonance spectroscopy study in social phobia. Biol Psychiatry 42:419–424. CrossRefPubMedGoogle Scholar
  304. Uchida RR, Del-Ben CM, Busatto GF, Duran FLS, Guimarães FS, Crippa JAS, Araújo D, Santos AC, Graeff FG (2008) Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study. Psychiatry Res 163:21–29. CrossRefPubMedGoogle Scholar
  305. Valente AA, Miguel EC, Castro CC, Amaro E, Duran FLS, Buchpiguel CA, Chitnis X, McGuire PK, Busatto GF (2005) Regional gray matter abnormalities in obsessive-compulsive disorder: a voxel-based morphometry study. Biol Psychiatry 58:479–487. CrossRefPubMedGoogle Scholar
  306. Van Ameringen M, Mancini C, Szechtman H, Nahmias C, Oakman JM, Hall GBC, Pipe B, Farvolden P (2004) A PET provocation study of generalized social phobia. Psychiatry Res 132:13–18. CrossRefPubMedGoogle Scholar
  307. van den Heuvel OA, Veltman DJ, Groenewegen HJ, Cath DC, van Balkom AJLM, van Hartskamp J, Barkhof F, van Dyck R (2005) Frontal-striatal dysfunction during planning in obsessive-compulsive disorder. Arch Gen Psychiatry 62:301–309. CrossRefPubMedGoogle Scholar
  308. Van der Linden G, van Heerden B, Warwick J, Wessels C, van Kradenburg J, Zungu-Dirwayi N, Stein DJ (2000) Functional brain imaging and pharmacotherapy in social phobia: single photon emission computed tomography before and after treatment with the selective serotonin reuptake inhibitor citalopram. Prog Neuro-Psychopharmacol Biol Psychiatry 24:419–438CrossRefGoogle Scholar
  309. van der Wee NJ, van Veen JF, Stevens H, van Vliet IM, van Rijk PP, Westenberg HG (2008) Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by 123I-beta-(4-iodophenyl)-tropane SPECT. J Nucl Med 49:757–763. CrossRefPubMedGoogle Scholar
  310. van Rooij SJH, Geuze E, Kennis M, Rademaker AR, Vink M (2015a) Neural correlates of inhibition and contextual cue processing related to treatment response in PTSD. Neuropsychopharmacology 40:667–675. CrossRefPubMedGoogle Scholar
  311. van Rooij SJH, Kennis M, Sjouwerman R, van den Heuvel MP, Kahn RS, Geuze E (2015b) Smaller hippocampal volume as a vulnerability factor for the persistence of post-traumatic stress disorder. Psychol Med 45:2737–2746. CrossRefPubMedGoogle Scholar
  312. Walitza S, Marinova Z, Grünblatt E, Lazic SE, Remschmidt H, Vloet TD, Wendland JR (2014) Trio study and meta-analysis support the association of genetic variation at the serotonin transporter with early-onset obsessive-compulsive disorder. Neurosci Lett 580:100–103. CrossRefPubMedCentralPubMedGoogle Scholar
  313. Wang Y, Zhang H, Li Y, Wang Z, Fan Q, Yu S, Lin Z, Xiao Z (2015) BDNF Val66Met polymorphism and plasma levels in Chinese Han population with obsessive-compulsive disorder and generalized anxiety disorder. J Affect Disord 186:7–12. CrossRefPubMedGoogle Scholar
  314. Wang W, Hou J, Qian S, Liu K, Li B, Li M, Peng Z, Xin K, Sun G (2016) Aberrant regional neural fluctuations and functional connectivity in generalized anxiety disorder revealed by resting-state functional magnetic resonance imaging. Neurosci Lett 624:78–84. CrossRefPubMedGoogle Scholar
  315. Warwick JM, Carey PD, Cassimjee N, Lochner C, Hemmings S, Moolman-Smook H, Beetge E, Dupont P, Stein DJ (2012) Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram. Metab Brain Dis 27:151–158. CrossRefPubMedGoogle Scholar
  316. Weber AM, Soreni N, Stanley JA, Greco A, Mendlowitz S, Szatmari P, Schachar R, Mannasis K, Pires P, Swinson R, Noseworthy MD (2014) Proton magnetic resonance spectroscopy of prefrontal white matter in psychotropic naïve children and adolescents with obsessive-compulsive disorder. Psychiatry Res 222:67–74. CrossRefPubMedGoogle Scholar
  317. Weinberg A, Olvet DM, Hajcak G (2010) Increased error-related brain activity in generalized anxiety disorder. Biol Psychol 85:472–480. CrossRefPubMedGoogle Scholar
  318. Wen S-L, Cheng M-H, Cheng M-F, Yue J-H, Wang H (2013) Pharmacotherapy response and regional cerebral blood flow characteristics in patients with obsessive-compulsive disorder. Behav Brain Funct 9:31. CrossRefPubMedCentralPubMedGoogle Scholar
  319. Whalen PJ, Johnstone T, Somerville LH, Nitschke JB, Polis S, Alexander AL, Davidson RJ, Kalin NH (2008) A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biol Psychiatry 63:858–863. CrossRefPubMedGoogle Scholar
  320. White S, Acierno R, Ruggiero KJ, Koenen KC, Kilpatrick DG, Galea S, Gelernter J, Williamson V, McMichael O, Vladimirov VI, Amstadter AB (2013) Association of CRHR1 variants and posttraumatic stress symptoms in hurricane exposed adults. J Anxiety Disord 27:678–683. CrossRefPubMedCentralPubMedGoogle Scholar
  321. Whiteside SP, Port JD, Abramowitz JS (2004) A meta-analysis of functional neuroimaging in obsessive-compulsive disorder. Psychiatry Res 132:69–79. CrossRefPubMedGoogle Scholar
  322. Wik G, Fredrikson M, Fischer H (1996) Cerebral correlates of anticipated fear: a PET study of specific phobia. Int J Neurosci 87:267–276CrossRefPubMedGoogle Scholar
  323. Wingo AP, Gibson G (2015) Blood gene expression profiles suggest altered immune function associated with symptoms of generalized anxiety disorder. Brain Behav Immun 43:184–191. CrossRefPubMedGoogle Scholar
  324. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21:655–679. CrossRefPubMedGoogle Scholar
  325. Wittmann A, Schlagenhauf F, Guhn A, Lueken U, Gaehlsdorf C, Stoy M, Bermpohl F, Fydrich T, Pfleiderer B, Bruhn H, Gerlach AL, Kircher T, Straube B, Wittchen HU, Arolt V, Heinz A, Ströhle A (2014) Anticipating agoraphobic situations: the neural correlates of panic disorder with agoraphobia. Psychol Med 44:2385–2396. CrossRefPubMedGoogle Scholar
  326. Wu JC, Buchsbaum MS, Hershey TG, Hazlett E, Sicotte N, Johnson JC (1991) PET in generalized anxiety disorder. Biol Psychiatry 29:1181–1199CrossRefPubMedGoogle Scholar
  327. Xie B, Wang B, Suo P, Kou C, Wang J, Meng X, Cheng L, Ma X, Yu Y (2011) Genetic association between BDNF gene polymorphisms and phobic disorders: a case-control study among mainland Han Chinese. J Affect Disord 132:239–242. CrossRefPubMedGoogle Scholar
  328. Xie P, Kranzler HR, Yang C, Zhao H, Farrer LA, Gelernter J (2013) Genome-wide association study identifies new susceptibility loci for posttraumatic stress disorder. Biol Psychiatry 74:656–663. CrossRefPubMedGoogle Scholar
  329. Yamanishi T, Nakaaki S, Omori IM, Hashimoto N, Shinagawa Y, Hongo J, Horikoshi M, Tohyama J, Akechi T, Soma T, Iidaka T, Furukawa TA (2009) Changes after behavior therapy among responsive and nonresponsive patients with obsessive-compulsive disorder. Psychiatry Res 172:242–250. CrossRefPubMedGoogle Scholar
  330. Yang Z-Y, Quan H, Peng Z-L, Zhong Y, Tan Z-J, Gong Q-Y (2015) Proton magnetic resonance spectroscopy revealed differences in the glutamate + glutamine/creatine ratio of the anterior cingulate cortex between healthy and pediatric post-traumatic stress disorder patients diagnosed after 2008 Wenchuan earthquake. Psychiatry Clin Neurosci 69:782–790. CrossRefPubMedGoogle Scholar
  331. Yassa MA, Hazlett RL, Stark CEL, Hoehn-Saric R (2012) Functional MRI of the amygdala and bed nucleus of the stria terminalis during conditions of uncertainty in generalized anxiety disorder. J Psychiatr Res 46:1045–1052. CrossRefPubMedCentralPubMedGoogle Scholar
  332. Yehuda R, Pratchett LC, Elmes MW, Lehrner A, Daskalakis NP, Koch E, Makotkine I, Flory JD, Bierer LM (2014) Glucocorticoid-related predictors and correlates of post-traumatic stress disorder treatment response in combat veterans. Interface Focus 4:20140048. CrossRefPubMedCentralPubMedGoogle Scholar
  333. Yevtushenko OO, Oros MM, Reynolds GP (2010) Early response to selective serotonin reuptake inhibitors in panic disorder is associated with a functional 5-HT1A receptor gene polymorphism. J Affect Disord 123:308–311. CrossRefPubMedGoogle Scholar
  334. Yoo HK, Kim MJ, Kim SJ, Sung YH, Sim ME, Lee YS, Song SY, Kee BS, Lyoo IK (2005) Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study. Eur J Neurosci 22:2089–2094. CrossRefPubMedGoogle Scholar
  335. Yoon S, Jun CS, Jeong HS, Lee S, Lim SM, Ma J, Ko E, Cho HB, Yeum T-S, Lyoo IK (2013) Altered cortical gyrification patterns in panic disorder: deficits and potential compensation. J Psychiatr Res 47:1446–1454. CrossRefPubMedGoogle Scholar
  336. You J-S, Hu S-Y, Chen B, Zhang H-G (2005) Serotonin transporter and tryptophan hydroxylase gene polymorphisms in Chinese patients with generalized anxiety disorder. Psychiatr Genet 15:7–11CrossRefPubMedGoogle Scholar
  337. Young KS, Burklund LJ, Torre JB, Saxbe D, Lieberman MD, Craske MG (2017) Treatment for social anxiety disorder alters functional connectivity in emotion regulation neural circuitry. Psychiatry Res 261:44–51. CrossRefPubMedCentralGoogle Scholar
  338. Zai G, Brandl EJ, Müller DJ, Richter MA, Kennedy JL (2014) Pharmacogenetics of antidepressant treatment in obsessive-compulsive disorder: an update and implications for clinicians. Pharmacogenomics 15:1147–1157. CrossRefPubMedGoogle Scholar
  339. Zai G, Zai CC, Arnold PD, Freeman N, Burroughs E, Kennedy JL, Richter MA (2015) Meta-analysis and association of brain-derived neurotrophic factor (BDNF) gene with obsessive-compulsive disorder. Psychiatr Genet 25:95–96. CrossRefPubMedGoogle Scholar
  340. Zhang Z, Fan Q, Bai Y, Wang Z, Zhang H, Xiao Z (2016) Brain Gamma-Aminobutyric Acid (GABA) concentration of the prefrontal lobe in unmedicated patients with obsessive-compulsive disorder: a research of magnetic resonance spectroscopy. Shanghai Arch Psychiatry 28:263–270. CrossRefPubMedGoogle Scholar
  341. Zhu H, Qiu C, Meng Y, Cui H, Zhang Y, Huang X, Zhang J, Li T, Gong Q, Zhang W, Lui S (2015a) Altered spontaneous neuronal activity in chronic posttraumatic stress disorder patients before and after a 12-week paroxetine treatment. J Affect Disord 174:257–264. CrossRefPubMedGoogle Scholar
  342. Zhu Y, Fan Q, Han X, Zhang H, Chen J, Wang Z, Zhang Z, Tan L, Xiao Z, Tong S, Maletic-Savatic M, Li Y (2015b) Decreased thalamic glutamate level in unmedicated adult obsessive-compulsive disorder patients detected by proton magnetic resonance spectroscopy. J Affect Disord 178:193–200. CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Neuropsychopharmacology Unit, Centre for Academic Psychiatry, Division of Brain SciencesImperial College LondonLondonUK
  2. 2.Department of PsychiatryUniversity of TartuTartuEstonia
  3. 3.Department of PsychiatryNorth Estonia Medical CentreTallinnEstonia
  4. 4.Department of PsychiatryTaichung Veterans General HospitalTaichungTaiwan

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