Details of Disease

General Information of Disease (ID: DISD3VNY)

Disease Name	Panic disorder
Synonyms	panic anxiety syndrome
Disease Class	6B01: Panic disorder
Definition	An anxiety disorder characterized by multiple unexpected panic attacks with persistent concern of recurring attacks. Panic disorder may or may not be accompanied by agoraphobia.
Disease Hierarchy	DISBI2BT: Anxiety disorder DISD3VNY: Panic disorder
ICD Code	ICD-11 ICD-11: 6B01 ICD-10 ICD-10: F41.0 ICD-9 ICD-9: 300.01, 300.21 Expand ICD-11 '6B01 Expand ICD-10 'F41.0 Expand ICD-9 300.01,300.21
Disease Identifiers	MONDO ID MONDO_0005383 MESH ID D016584 UMLS CUI C0030319 MedGen ID 14588 SNOMED CT ID 371631005

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 7 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Alprazolam	DMC7XDN	Approved	Small molecular drug	[1]
Clonazepam	DMTO13J	Approved	Small molecular drug	[2]
Fluoxetine	DM3PD2C	Approved	Small molecular drug	[3]
Lorazepam	DM84ZXF	Approved	Small molecular drug	[4]
Paroxetine	DM5PVQE	Approved	Small molecular drug	[5]
Sertraline	DM0FB1J	Approved	Small molecular drug	[6]
Venlafaxine	DMR6QH0	Approved	Small molecular drug	[7]
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⏷ Show the Full List of 7 Drug(s)

This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
NBTX-001	DM3MJUS	Phase 2/3	NA	[8]
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This Disease is Treated as An Indication in 2 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
DOV-51892	DMQIK9S	Investigative	NA	[9]
INT-0015/2008	DMA841R	Investigative	NA	[10]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 32 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GRM2	TTXJ47W	Limited	Biomarker	[11]
SRD5A1	TTTU72V	Limited	Biomarker	[12]
DRD1	TTZFYLI	moderate	Genetic Variation	[13]
DRD4	TTE0A2F	moderate	Genetic Variation	[14]
NPY5R	TTY6EWA	moderate	Biomarker	[15]
ASIC1	TTRJYB6	Strong	Genetic Variation	[16]
ASIC2	TTVMWLP	Strong	Genetic Variation	[17]
AVPR1B	TTL9MHW	Strong	Genetic Variation	[18]
BDKRB1	TTG5QIA	Strong	Genetic Variation	[19]
CCKAR	TTCG0AL	Strong	Genetic Variation	[20]
CRHR2	TTIY658	Strong	Biomarker	[21]
ELK3	TT5OJMV	Strong	Biomarker	[22]
EPHB1	TT8MDAC	Strong	Biomarker	[22]
GABRA5	TTNZPQ1	Strong	Biomarker	[23]
GAD1	TTKGEP3	Strong	Biomarker	[24]
HCRT	TTU5HJP	Strong	Biomarker	[25]
HCRTR2	TT9N02I	Strong	Genetic Variation	[26]
HTR2A	TTJQOD7	Strong	Genetic Variation	[27]
HTR3A	TTPC4TU	Strong	Biomarker	[28]
INS	TTZOPHG	Strong	Biomarker	[29]
MAOA	TT3WG5C	Strong	Biomarker	[30]
NAGLU	TTDM6HZ	Strong	Biomarker	[31]
NPSR1	TTV1C0Z	Strong	Genetic Variation	[32]
PEPD	TTLZXI0	Strong	Genetic Variation	[33]
PTK7	TTXH2ZN	Strong	Biomarker	[34]
RGS2	TTKB7T3	Strong	Genetic Variation	[35]
TPH1	TTZSJHV	Strong	Genetic Variation	[27]
TPH2	TT3KLDP	Strong	Genetic Variation	[36]
TSPO	TTPTXIN	Strong	Genetic Variation	[12]
ADRA2A	TTWG9A4	Definitive	Biomarker	[37]
CRHR1	TT7EFHR	Definitive	Posttranslational Modification	[38]
HCRTR1	TT60Q8D	Definitive	Genetic Variation	[25]
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⏷ Show the Full List of 32 DTT(s)

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC43A2	DTK02I1	Strong	Genetic Variation	[39]
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This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
AKR1C1	DE7P2FB	Limited	Biomarker	[12]
SCLY	DEH4TD6	moderate	Genetic Variation	[40]
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This Disease Is Related to 43 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DYNLL2	OTLIT58K	Limited	Biomarker	[41]
MPEG1	OT7DAO0F	Limited	Genetic Variation	[42]
CBLIF	OTNE20WU	moderate	Biomarker	[43]
CREM	OTJIJ5AL	moderate	Genetic Variation	[44]
TAL1	OTX4K6QZ	moderate	Genetic Variation	[40]
ANO2	OT650E98	Strong	Biomarker	[45]
CALCOCO1	OT1PAIN0	Strong	Genetic Variation	[33]
CDS1	OT2F591M	Strong	Biomarker	[46]
DAOA	OT7NFEO6	Strong	Genetic Variation	[47]
DEAF1	OTCLX3ZW	Strong	Genetic Variation	[48]
DGKH	OTYNPJ4B	Strong	Biomarker	[49]
DTNBP1	OT9UQT2S	Strong	Genetic Variation	[50]
EFHC2	OTI459M8	Strong	Genetic Variation	[51]
GABBR1	OTU5A52J	Strong	Genetic Variation	[52]
GABRA6	OTX4UC3O	Strong	Genetic Variation	[53]
GABRB3	OT80C3D4	Strong	Biomarker	[23]
GANC	OTLJSCYV	Strong	Genetic Variation	[54]
GFRA4	OTOLGKQM	Strong	Genetic Variation	[54]
GLRB	OTF37UG4	Strong	Genetic Variation	[40]
GPM6A	OT8G13EG	Strong	Biomarker	[55]
GPR65	OTCF5O4G	Strong	Altered Expression	[56]
IKBKE	OT5VYOSM	Strong	Biomarker	[57]
LDHB	OT9B1CT3	Strong	Biomarker	[58]
LRRC8E	OTUZTANF	Strong	Biomarker	[59]
MANEA	OTV7L8I6	Strong	Biomarker	[60]
NBAS	OTW9IBRI	Strong	Biomarker	[31]
NPS	OTEG25A2	Strong	Biomarker	[61]
PKP1	OT9HSQ8F	Strong	Genetic Variation	[33]
PLA2G4E	OTN2RVX8	Strong	Genetic Variation	[54]
PRDM11	OT6DX554	Strong	Genetic Variation	[33]
PSG5	OTHTU98X	Strong	Biomarker	[62]
RGS7	OTDQA90X	Strong	Genetic Variation	[63]
SCN7A	OTK05PXY	Strong	Biomarker	[31]
SDK2	OTTBK3MH	Strong	Genetic Variation	[33]
SGCE	OT9F17JB	Strong	Genetic Variation	[64]
SGCZ	OTVGTEOD	Strong	Genetic Variation	[33]
SNAPC2	OTN0EL6L	Strong	Genetic Variation	[59]
SNRNP70	OTP52YZ3	Strong	Genetic Variation	[44]
TMEM132D	OTV6I4Z0	Strong	Genetic Variation	[65]
TMEM132E	OTHCX3RI	Strong	Genetic Variation	[66]
TMEM98	OTKDUEED	Strong	Biomarker	[66]
TSHZ1	OTYQ9ECW	Strong	Genetic Variation	[67]
ARSI	OTIANNWW	Definitive	Genetic Variation	[68]
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⏷ Show the Full List of 43 DOT(s)

References

1	Alprazolam FDA Label
2	Clonazepam FDA Label
3	Fluoxetine FDA Label
4	Lorazepam FDA Label
5	Paroxetine FDA Label
6	Sertraline FDA Label
7	Venlafaxine FDA Label
8	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 415).
10	The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
11	Panic results in unique molecular and network changes in the amygdala that facilitate fear responses.Mol Psychiatry. 2020 Feb;25(2):442-460. doi: 10.1038/s41380-018-0119-0. Epub 2018 Aug 14.
12	Gender-specific association of variants in the AKR1C1 gene with dimensional anxiety in patients with panic disorder: additional evidence for the importance of neurosteroids in anxiety?.Depress Anxiety. 2014 Oct;31(10):843-50. doi: 10.1002/da.22229. Epub 2014 Jan 3.
13	Association testing of panic disorder candidate genes using CCK-4 challenge in healthy volunteers.Neurosci Lett. 2008 Dec 3;446(2-3):88-92. doi: 10.1016/j.neulet.2008.09.052.
14	Idiopathic environmental intolerance: increased prevalence of panic disorder-associated cholecystokinin B receptor allele 7.J Allergy Clin Immunol. 2001 May;107(5):887-90. doi: 10.1067/mai.2001.114798.
15	Meta-analysis of genome-wide association studies for panic disorder in the Japanese population.Transl Psychiatry. 2012 Nov 13;2(11):e186. doi: 10.1038/tp.2012.89.
16	Amiloride-sensitive cation channel 2 genotype affects the response to a carbon dioxide panic challenge.J Psychopharmacol. 2017 Oct;31(10):1294-1301. doi: 10.1177/0269881116686880. Epub 2017 Jan 25.
17	A genome-wide study of panic disorder suggests the amiloride-sensitive cation channel 1 as a candidate gene.Eur J Hum Genet. 2012 Jan;20(1):84-90. doi: 10.1038/ejhg.2011.148. Epub 2011 Aug 3.
18	Combined effects of exonic polymorphisms in CRHR1 and AVPR1B genes in a case/control study for panic disorder.Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1196-204. doi: 10.1002/ajmg.b.30750.
19	Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment.Am J Med Genet B Neuropsychiatr Genet. 2009 Sep 5;150B(6):808-16. doi: 10.1002/ajmg.b.30902.
20	Gene variations in the cholecystokinin system in patients with panic disorder.Psychiatr Genet. 2010 Apr;20(2):59-64. doi: 10.1097/YPG.0b013e32833511a8.
21	The blockage of ventromedial hypothalamus CRF type 2 receptors impairs escape responses in the elevated T-maze.Behav Brain Res. 2017 Jun 30;329:41-50. doi: 10.1016/j.bbr.2017.04.030. Epub 2017 Apr 21.
22	A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism.Mol Psychiatry. 2017 Jan;22(1):134-141. doi: 10.1038/mp.2016.40. Epub 2016 Apr 5.
23	Evidence for linkage and association of GABRB3 and GABRA5 to panic disorder.Neuropsychopharmacology. 2014 Sep;39(10):2423-31. doi: 10.1038/npp.2014.92. Epub 2014 May 23.
24	Does CBT for anxiety-related disorders alter suicidal ideation? Findings from a naturalistic sample.J Anxiety Disord. 2018 Oct;59:10-16. doi: 10.1016/j.janxdis.2018.08.001. Epub 2018 Aug 8.
25	Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes.Transl Psychiatry. 2019 Feb 4;9(1):75. doi: 10.1038/s41398-019-0415-8.
26	Panic disorder is associated with the Val308Iso polymorphism in the hypocretin receptor gene.Psychiatr Genet. 2011 Apr;21(2):85-9. doi: 10.1097/YPG.0b013e328341a3db.
27	Candidate genes in panic disorder: meta-analyses of 23 common variants in major anxiogenic pathways.Mol Psychiatry. 2016 May;21(5):665-79. doi: 10.1038/mp.2015.138. Epub 2015 Sep 22.
28	Serotonin receptor 3A (HTR3A) gene is associated with personality traits, but not panic disorder.Psychiatr Genet. 2008 Feb;18(1):44. doi: 10.1097/YPG.0b013e3282f02099.
29	Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose-dependent increase in plasma C-peptide levels. Psychopharmacology (Berl). 2002 Jun;161(4):396-403. doi: 10.1007/s00213-002-1044-z. Epub 2002 Apr 17.
30	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. 2019 Mar;269(2):161-170. doi: 10.1007/s00406-017-0823-9. Epub 2017 Jul 15.
31	An association of NAG levels and a mutation of the CCK gene in panic disorder patients.Psychiatry Res. 1998 Aug 17;80(2):149-53. doi: 10.1016/s0165-1781(98)00063-8.
32	Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.Neuroimage Clin. 2019;24:102029. doi: 10.1016/j.nicl.2019.102029. Epub 2019 Oct 21.
33	Genome-wide association study of panic disorder in the Japanese population.J Hum Genet. 2009 Feb;54(2):122-6. doi: 10.1038/jhg.2008.17. Epub 2009 Jan 23.
34	The effect of 6-week treatment with escitalopram on CCK-4 challenge: a placebo-controlled study in CCK-4-sensitive healthy volunteers.Eur Neuropsychopharmacol. 2013 Jul;23(7):645-52. doi: 10.1016/j.euroneuro.2012.08.011. Epub 2012 Aug 29.
35	Novel developments in genetic and epigenetic mechanisms of anxiety.Curr Opin Psychiatry. 2016 Jan;29(1):32-8. doi: 10.1097/YCO.0000000000000219.
36	Associations between prefrontal -aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women.Int J Neuropsychopharmacol. 2013 Sep;16(8):1707-17. doi: 10.1017/S1461145713000254. Epub 2013 Apr 3.
37	Heart rate and QT interval variability: abnormal alpha-2 adrenergic function in patients with panic disorder.Psychiatry Res. 2003 Dec 1;121(2):185-96. doi: 10.1016/s0165-1781(03)00235-x.
38	CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder?.Eur Neuropsychopharmacol. 2017 Apr;27(4):360-371. doi: 10.1016/j.euroneuro.2017.01.005. Epub 2017 Feb 21.
39	The DNA methylome in panic disorder: a case-control and longitudinal psychotherapy-epigenetic study.Transl Psychiatry. 2019 Nov 21;9(1):314. doi: 10.1038/s41398-019-0648-6.
40	GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder.Mol Psychiatry. 2017 Oct;22(10):1431-1439. doi: 10.1038/mp.2017.2. Epub 2017 Feb 7.
41	An association analysis of murine anxiety genes in humans implicates novel candidate genes for anxiety disorders.Biol Psychiatry. 2008 Oct 15;64(8):672-680. doi: 10.1016/j.biopsych.2008.06.002. Epub 2008 Jul 17.
42	Human nuclear transcription factor gene CREM: genomic organization, mutation screening, and association analysis in panic disorder.Am J Med Genet B Neuropsychiatr Genet. 2003 Feb;117B(1):70-8. doi: 10.1002/ajmg.b.10018.
43	Cytokine alterations in panic disorder: A systematic review.J Affect Disord. 2018 Mar 1;228:91-96. doi: 10.1016/j.jad.2017.11.094. Epub 2017 Dec 7.
44	Investigation of polymorphisms in the CREM gene in panic disorder.Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):111-5. doi: 10.1002/ajmg.b.20121.
45	A survey of putative anxiety-associated genes in panic disorder patients with and without bladder symptoms.Psychiatr Genet. 2012 Dec;22(6):271-8. doi: 10.1097/YPG.0b013e3283586248.
46	Dissociative symptoms as measured by the Cambridge Depersonalization Scale in patients with a bipolar disorder.J Affect Disord. 2020 Feb 15;263:187-192. doi: 10.1016/j.jad.2019.11.137. Epub 2019 Nov 30.
47	Investigation of the DAOA/G30 locus in panic disorder.Mol Psychiatry. 2005 May;10(5):428-9. doi: 10.1038/sj.mp.4001598.
48	5-HT1A receptors, gene repression, and depression: guilt by association.Neuroscientist. 2004 Dec;10(6):575-93. doi: 10.1177/1073858404267382.
49	Whole-exome sequencing implicates DGKH as a risk gene for panic disorder in the Faroese population.Am J Med Genet B Neuropsychiatr Genet. 2016 Dec;171(8):1013-1022. doi: 10.1002/ajmg.b.32464. Epub 2016 Jun 3.
50	Genetic polymorphism in DTNBP1 gene is associated with methamphetamine-induced panic disorder.J Addict Med. 2014 Nov-Dec;8(6):431-7. doi: 10.1097/ADM.0000000000000075.
51	Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance.Neurosci Lett. 2009 Mar 6;452(1):84-6. doi: 10.1016/j.neulet.2009.01.036. Epub 2009 Jan 19.
52	Exonic variants of the GABA(B) receptor gene and panic disorder.Psychiatr Genet. 2000 Dec;10(4):191-4. doi: 10.1097/00041444-200010040-00007.
53	Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder.Int J Psychiatry Clin Pract. 2015;19(3):192-200. doi: 10.3109/13651501.2015.1043133. Epub 2015 May 14.
54	Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder.Transl Psychiatry. 2018 Feb 2;8(1):41. doi: 10.1038/s41398-017-0088-0.
55	A single gene defect causing claustrophobia.Transl Psychiatry. 2013 Apr 30;3(4):e254. doi: 10.1038/tp.2013.28.
56	Acid-sensing T cell death associated gene-8 receptor expression in panic disorder.Brain Behav Immun. 2018 Jan;67:36-41. doi: 10.1016/j.bbi.2017.07.014. Epub 2017 Jul 20.
57	Polymorphisms of IKBKE gene are associated with major depressive disorder and panic disorder.Brain Behav. 2015 Apr;5(4):e00314. doi: 10.1002/brb3.314. Epub 2015 Feb 13.
58	Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder.Am J Med Genet B Neuropsychiatr Genet. 2003 Feb;117B(1):11-7. doi: 10.1002/ajmg.b.10015.
59	Association between genes on chromosome 19p13.2 and panic disorder.Psychiatr Genet. 2016 Dec;26(6):287-292. doi: 10.1097/YPG.0000000000000147.
60	The -endomannosidase gene (MANEA) is associated with panic disorder and social anxiety disorder.Transl Psychiatry. 2014 Jan 28;4(1):e353. doi: 10.1038/tp.2013.122.
61	Modulation of prefrontal functioning in attention systems by NPSR1 gene variation.Neuroimage. 2015 Jul 1;114:199-206. doi: 10.1016/j.neuroimage.2015.03.064. Epub 2015 Apr 2.
62	Calibrating actigraphy to improve sleep efficiency estimates.J Sleep Res. 2018 Aug;27(4):e12613. doi: 10.1111/jsr.12613. Epub 2017 Oct 24.
63	Association analysis of Rgs7 variants with panic disorder.J Neural Transm (Vienna). 2009 Nov;116(11):1523-8. doi: 10.1007/s00702-008-0097-5. Epub 2008 Sep 2.
64	Psychiatric symptoms in myoclonus-dystonia syndrome are just concomitant features regardless of the SGCE gene mutation.Parkinsonism Relat Disord. 2017 Sep;42:73-77. doi: 10.1016/j.parkreldis.2017.06.014. Epub 2017 Jun 23.
65	Polymorphism in Tmem132d regulates expression and anxiety-related behavior through binding of RNA polymerase II complex.Transl Psychiatry. 2018 Jan 10;8(1):1. doi: 10.1038/s41398-017-0025-2.
66	Are TMEM genes potential candidate genes for panic disorder?.Psychiatr Genet. 2014 Feb;24(1):37-41. doi: 10.1097/YPG.0000000000000022.
67	Association study of 90 candidate gene polymorphisms in panic disorder.Psychiatr Genet. 2005 Mar;15(1):17-24. doi: 10.1097/00041444-200503000-00004.
68	White matter connectivity differences between treatment responders and non-responders in patients with panic disorder.J Affect Disord. 2020 Jan 1;260:527-535. doi: 10.1016/j.jad.2019.09.032. Epub 2019 Sep 4.