title: Towards new approaches to disorders of fear and anxiety.
abstract: Fear and anxiety are debilitating conditions that affect a significant number of individuals in their lifetimes. Understanding underlying mechanisms of these disorders affords us the possibility of therapeutic intervention. Such clarity in terms of mechanism and intervention can only come from an amalgamation of research from human to animal studies that attempt to mimic the human condition, both of which are discussed in this review. We begin by presenting an outline of our current understanding of the neurobiological basis of fear and anxiety. This outline spans various levels of organization that include the circuitry, molecular pathways, genetic and epigenetic components of fear and anxiety. Using these organizational levels as a scaffold, we then discuss strategies that are currently used to ameliorate these disorders, and forecast future interventions that hold therapeutic promise. Among these newer promising treatments, we include, optogenetic, pharmacological, and extinction-based approaches, as well as lifestyle modifications, with combinatorial treatment regimens of these holding the most promise.
authors: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Brian G
authors: BG
authors: Dias
authors: Sunayana B
authors: SB
authors: Banerjee
authors: Jared V
authors: JV
authors: Goodman
authors: Kerry J
authors: KJ
authors: Ressler
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology*; D001008:Anxiety Disorders / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D001921:Brain / Q000503:physiopathology*; D044127:Epigenesis, Genetic; D005239:Fear / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009462:Neurology / Q000639:trends
references: J Abnorm Psychol. 2010 May;119(2):320-30
references: 20455605
references: Nat Neurosci. 2011 Aug 14;14(9):1115-7
references: 21841775
references: Psychopharmacology (Berl). 1986;88(2):147-52
references: 3081925
references: Am J Psychiatry. 2002 Oct;159(10):1675-81
references: 12359672
references: Behav Brain Res. 1997 Mar;84(1-2):241-6
references: 9079788
references: Nat Neurosci. 2007 Sep;10(9):1116-24
references: 17726478
references: Neuroscience. 1988 Oct;27(1):1-39
references: 3059226
references: Arch Gen Psychiatry. 1999 Oct;56(10):921-6
references: 10530634
references: World J Biol Psychiatry. 2010 Mar;11(2 Pt 2):220-30
references: 20218785
references: Cell. 2012 Jul 6;150(1):12-27
references: 22770212
references: Trends Pharmacol Sci. 2008 Oct;29(10):493-8
references: 18755516
references: Behav Brain Res. 2007 Apr 16;179(1):1-18
references: 17306892
references: Biol Psychiatry. 2008 Jun 15;63(12):1118-26
references: 18313643
references: Neurosci Biobehav Rev. 2012 Aug;36(7):1773-802
references: 22230704
references: Horm Behav. 1997 Jun;31(3):197-211
references: 9213134
references: Science. 2009 May 15;324(5929):951-5
references: 19342552
references: Physiol Behav. 2012 Dec 5;107(5):699-710
references: 22429904
references: J Neurosci. 2011 Feb 2;31(5):1802-10
references: 21289190
references: Nat Rev Neurosci. 2004 Nov;5(11):844-52
references: 15496862
references: Curr Psychiatry Rep. 2010 Aug;12(4):313-26
references: 20549395
references: Biol Psychiatry. 1997 Sep 15;42(6):461-71
references: 9285082
references: Nature. 2011 Mar 17;471(7338):358-62
references: 21389985
references: Am J Psychiatry. 2011 Feb;168(2):163-72
references: 21123312
references: Neuron. 2007 Oct 4;56(1):19-32
references: 17920012
references: J Psychopharmacol. 2012 Jan;26(1):23-39
references: 21768162
references: Ann N Y Acad Sci. 2003 Dec;1008:112-21
references: 14998877
references: Biol Psychiatry. 2000 Oct 15;48(8):813-29
references: 11063977
references: Biol Psychiatry. 2006 Oct 1;60(7):760-6
references: 16631127
references: Mol Psychiatry. 2012 Mar;17(3):239-41
references: 21912390
references: J Affect Disord. 2000 Dec;61(3):137-59
references: 11163418
references: Int J Emerg Ment Health. 2005 Winter;7(1):49-57
references: 15869081
references: Nat Neurosci. 2005 Sep;8(9):1263-8
references: 16116447
references: Nat Neurosci. 2011 Mar;14(3):387-97
references: 21278729
references: Drug Discov Today. 2009 Oct;14(19-20):942-8
references: 19577000
references: Learn Mem. 2012 Aug 16;19(9):359-68
references: 22904366
references: Nat Rev Drug Discov. 2012 Feb 01;11(2):141-68
references: 22293568
references: Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16330-5
references: 22992651
references: Annu Rev Psychol. 2006;57:27-53
references: 16318588
references: Nature. 2000 Aug 17;406(6797):722-6
references: 10963596
references: Neurochem Res. 2008 Oct;33(10):1925-32
references: 18386176
references: Neuropsychopharmacology. 2010 Jan;35(1):105-35
references: 19693004
references: Nature. 2012 Mar 22;484(7394):381-5
references: 22441246
references: Mol Psychiatry. 2013 Jul;18(7):742-3
references: 22776899
references: Biol Psychiatry. 2003 Nov 1;54(9):947-9
references: 14573324
references: Mol Psychiatry. 2013 Aug;18(8):937-42
references: 22869035
references: Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2675-80
references: 20133801
references: Arch Gen Psychiatry. 2005 Jun;62(6):593-602
references: 15939837
references: Science. 2006 Oct 6;314(5796):140-3
references: 17023662
references: Neuroscience. 2009 Nov 24;164(1):272-87
references: 19540311
references: Am J Psychiatry. 2001 Oct;158(10):1568-78
references: 11578982
references: Biol Psychiatry. 2010 Sep 1;68(5):408-15
references: 20673872
references: Neuropharmacology. 2012 Jan;62(1):42-53
references: 21889518
references: Annu Rev Neurosci. 1992;15:353-75
references: 1575447
references: Eur J Psychotraumatol. 2011;2:
references: 22893803
references: Depress Anxiety. 2000;12 Suppl 1:2-19
references: 11098410
references: Nature. 2009 May 7;459(7243):55-60
references: 19424149
references: Curr Biol. 2007 Oct 23;17(20):R868-74
references: 17956742
references: Evid Based Complement Alternat Med. 2012;2012:809653
references: 22969831
references: Neuropsychopharmacology. 2012 Nov;37(12):2740-6
references: 22871912
references: Curr Opin Neurobiol. 2010 Apr;20(2):231-5
references: 20303254
references: Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12692-7
references: 20615999
references: Psychophysiology. 1991 Sep;28(5):588-95
references: 1758934
references: Behav Neurosci. 2004 Oct;118(5):916-24
references: 15506874
references: Behav Brain Res. 2008 Sep 1;192(1):70-87
references: 18353453
references: Science. 2010 Feb 12;327(5967):863-6
references: 20075215
references: Neuropsychopharmacology. 2010 Jan;35(1):169-91
references: 19625997
references: Biol Psychiatry. 2007 Sep 1;62(5):446-54
references: 17217927
references: Nature. 2002 Nov 7;420(6911):70-4
references: 12422216
references: J Clin Psychiatry. 2012 Apr;73(4):533-7
references: 22579153
references: Biol Psychiatry. 2005 Jan 1;57(1):33-43
references: 15607298
references: J Psychopharmacol. 2000 Mar;14(1):40-5
references: 10757252
references: Depress Anxiety. 2013 Mar;30(3):251-8
references: 23280952
references: Arch Gen Psychiatry. 2004 Nov;61(11):1136-44
references: 15520361
references: Nature. 2011 Feb 24;470(7335):492-7
references: 21350482
references: Nature. 2011 Jul 27;477(7363):171-8
references: 21796121
references: J Neurosci. 2002 Mar 15;22(6):2343-51
references: 11896173
references: Eur Neuropsychopharmacol. 2011 Jul;21(7):532-44
references: 21237620
references: Proc Natl Acad Sci U S A. 2012 May 29;109(22):8764-9
references: 22586125
references: Annu Rev Neurosci. 2000;23:155-84
references: 10845062
references: Nature. 2010 Jan 7;463(7277):49-53
references: 20010606