Browse > Article
http://dx.doi.org/10.24986/anxmod.2019.15.2.122

Associations of Ubiquitin-Specific Protease Genes with Resilience and Social Anxiety in Healthy Youths  

Seo, Jun Ho (Institute of Behavioral Science in Medicine & Department of Psychiatry, Yonsei University College of Medicine)
Park, Chun Il (Institute of Behavioral Science in Medicine & Department of Psychiatry, Yonsei University College of Medicine)
Kim, Se Joo (Institute of Behavioral Science in Medicine & Department of Psychiatry, Yonsei University College of Medicine)
Kang, Jee In (Institute of Behavioral Science in Medicine & Department of Psychiatry, Yonsei University College of Medicine)
Publication Information
Anxiety and mood / v.15, no.2, 2019 , pp. 122-126 More about this Journal
Abstract
Objective : Dynamic proteolysis, through the ubiquitin-proteasome system, is an important molecular mechanism for the constant regulation of synaptic plasticity and stress responses in humans. In this study, we examined whether genetic variants in the ubiquitin-specific peptidase (USP) genes were associated with psychological traits of resilience and susceptibility to neuropsychiatric disorders for each gender. Methods : A total of 344 Korean healthy youths (190 males, 154 females) were included in the study. A genotyping of rs2241646 of USP2 and rs346006 of USP46 was performed. The Connor-Davidson Resilience Scale and Brief Fear of Negative Evaluation Scale were administered for measuring trait resilience and social anxiety, respectively. The genetic associations of the USP variants were tested using multiple analyses of covariance with psychological traits as dependent variables after controlling for age in each gender. Results : For USP2 rs2241646, women with the TT genotype showed significantly higher resilience and lower social anxiety, as compared to those carrying the C allele. There were no associations between USP46 rs346005 and the psychological traits in both genders. Conclusions : The present study showed a possible genetic association between the USP2 rs2241646 and stress resilience and trait anxiety in women. The findings suggest that ubiquitin-proteasome system may be related to the resilience and susceptibility to stress-related neuropsychiatric disorders such as anxiety disorders, possibly through the regulation of dynamic proteolysis responses to stress.
Keywords
Resilience; Social anxiety; Ubiquitin-proteasome system; Ubiquitin-specific peptidase (USP); Genetic association study;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Gadhave K, Bolshette N, Ahire A, Pardeshi R, Thakur K, Trandafir C, et al. The ubiquitin proteasomal system: a potential target for the management of Alzheimer's disease. J Cell Mol Med 2016;20:1392-1407.   DOI
2 Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 2009;459:569-573.   DOI
3 Louros SR, Osterweil EK. Perturbed proteostasis in autism spectrum disorders. J Neurochem 2016;139:1081-1092.   DOI
4 Chang S, Fang K, Zhang K, Wang J. Network-Based Analysis of Schizophrenia Genome-Wide Association Data to Detect the Joint Functional Association Signals. PLoS One 2015;10:e0133404.   DOI
5 Lin CY, Sawa A, Jaaro-Peled H. Better understanding of mechanisms of schizophrenia and bipolar disorder: from human gene expression profiles to mouse models. Neurobiol Dis 2012;45:48-56.   DOI
6 Fukuo Y, Kishi T, Kushima I, Yoshimura R, Okochi T, Kitajima T, et al. Possible association between ubiquitin-specific peptidase 46 gene and major depressive disorders in the Japanese population. J Affect Disord 2011;133:150-157.   DOI
7 Imai S, Mamiya T, Tsukada A, Sakai Y, Mouri A, Nabeshima T, et al. Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system. PLoS One 2012;7:e39084.   DOI
8 Tomida S, Mamiya T, Sakamaki H, Miura M, Aosaki T, Masuda M, et al. Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests. Nat Genet 2009;41:688-695.   DOI
9 Boo YJ, Park CI, Kim HW, Kim SJ, Kang JI. Possible Association of the Ubiquitin-Specific Peptidase 46 Gene (USP46) with Affective Temperamental Traits in Healthy Korean Volunteers. Psychiatry Investig 2019;16:87-92.   DOI
10 Hjemdal O, Aune T, Reinfjell T, Stiles TC, Friborg O. Resilience as a predictor of depressive symptoms: a correlational study with young adolescents. Clin Child Psychol Psychiatry 2007;12:91-104.   DOI
11 Collins KA, Westra HA, Dozois DJ, Stewart SH. The validity of the brief version of the Fear of Negative Evaluation Scale. J Anxiety Disord 2005;19:345-359.   DOI
12 Sato T, McCann D, Ferguson-Isaac C. Sociotropy-autonomy and situation-specific anxiety. Psychol Rep 2004;94:67-76.   DOI
13 O'Connor LE, Berry JW, Weiss J, Gilbert P. Guilt, fear, submission, and empathy in depression. J Affect Disord 2002;71:19-27.   DOI
14 Stojkovic K, Wing SS, Cermakian N. A central role for ubiquitination within a circadian clock protein modification code. Front Mol Neurosci 2014;7:69.
15 Yang Y, Duguay D, Bedard N, Rachalski A, Baquiran G, Na CH, et al. Regulation of behavioral circadian rhythms and clock protein PER1 by the deubiquitinating enzyme USP2. Biol Open 2012;1:789-801.   DOI
16 Yang Y, Duguay D, Fahrenkrug J, Cermakian N, Wing SS. USP2 regulates the intracellular localization of PER1 and circadian gene expression. J Biol Rhythms 2014;29:243-256.   DOI
17 First MB, Spitzer R, L GM, Williams JBW. Structured Clinical Interview for DSM-IV Axis I Disorders, Clinical Version (SCID-CV). Washington, D.C. : American Psychiatric Press, Inc.;1996.
18 Connor KM, Davidson JR. Development of a new resilience scale: the Connor-Davidson Resilience Scale (CD-RISC). Depress Anxiety 2003;18:76-82.   DOI
19 Leary MR. A brief version of the Fear of Negative Evaluation Scale. Personality and Social Psychology Bulletin 1983;9:371-375.   DOI
20 Lee JY, Choi CH. A Study of the Reliability and the Validity of the Korean versions of Social Phobia Scales (K-SAD, K-FNE). Korean Journal of Clinical Psychology 1997;16:251-264.
21 Baek HS, Lee KU, Joo EJ, Lee MY, Choi KS. Reliability and validity of the korean version of the connor-davidson resilience scale. Psychiatry Investig 2010;7:109-115.   DOI
22 Jung YE, Min JA, Shin AY, Han SY, Lee KU, Kim TS, et al. The Korean version of the Connor-Davidson Resilience Scale: an extended validation. Stress Health 2012;28:319-326.   DOI
23 Karatsoreos IN, McEwen BS. Psychobiological allostasis: resistance, resilience and vulnerability. Trends Cogn Sci 2011;15:576-584.   DOI
24 Weeks JW, Heimberg RG, Fresco DM, Hart TA, Turk CL, Schneier FR, et al. Empirical validation and psychometric evaluation of the Brief Fear of Negative Evaluation Scale in patients with social anxiety disorder. Psychol Assess 2005;17:179-190.   DOI
25 Jin HS, Hong KW, Lim JE, Hwang SY, Lee SH, Shin C, et al. Genetic variations in the sodium balance-regulating genes ENaC, NEDD4L, NDFIP2 and USP2 influence blood pressure and hypertension. Kidney Blood Press Res 2010;33:15-23.   DOI
26 Cajigas IJ, Will T, Schuman EM. Protein homeostasis and synaptic plasticity. EMBO J 2010;29:2746-2752.   DOI
27 McClung CA. Circadian genes, rhythms and the biology of mood disorders. Pharmacol Ther 2007;114:222-232.   DOI
28 Eszlari N, Millinghoffer A, Petschner P, Gonda X, Baksa D, Pulay AJ, et al. Genome-wide association analysis reveals KCTD12 and miR-383-binding genes in the background of rumination. Transl Psychiatry 2019;9:119.   DOI
29 Li C, Zhang J, Xu H, Chang M, Lv C, Xue W, et al. Retigabine ameliorates acute stress-induced impairment of spatial memory retrieval through regulating USP2 signaling pathways in hippocampal CA1 area. Neuropharmacology 2018;135:151-162.   DOI
30 Kyoung MH, Min JA, Chae JH. Relationship of Affective Symptoms and Resilience with Childhood Abuse in Patients with Depressive or Anxiety disorders. Anxiety and Mood 2013;9:68-73.
31 Li Q, Korte M, Sajikumar S. Ubiquitin-Proteasome System Inhibition Promotes Long-Term Depression and Synaptic Tagging/Capture. Cereb Cortex 2016;26:2541-2548.   DOI
32 Cheon S, Dean M, Chahrour M. The ubiquitin proteasome pathway in neuropsychiatric disorders. Neurobiol Learn Mem 2018.
33 Nalepa G, Rolfe M, Harper JW. Drug discovery in the ubiquitinproteasome system. Nat Rev Drug Discov 2006;5:596-613.   DOI
34 Dong C, Bach SV, Haynes KA, Hegde AN. Proteasome modulates positive and negative translational regulators in long-term synaptic plasticity. J Neurosci 2014;34:3171-3182.   DOI
35 Cai F, Frey JU, Sanna PP, Behnisch T. Protein degradation by the proteasome is required for synaptic tagging and the heterosynaptic stabilization of hippocampal late-phase long-term potentiation. Neuroscience 2010;169:1520-1526.   DOI
36 Kowalski JR, Juo P. The role of deubiquitinating enzymes in synaptic function and nervous system diseases. Neural Plast 2012;2012:892749.   DOI
37 Todi SV, Paulson HL. Balancing act: deubiquitinating enzymes in the nervous system. Trends Neurosci 2011;34:370-382.   DOI
38 Hegde AN. The ubiquitin-proteasome pathway and synaptic plasticity. Learn Mem 2010;17:314-327.   DOI
39 Lam YA, Pickart CM, Alban A, Landon M, Jamieson C, Ramage R, et al. Inhibition of the ubiquitin-proteasome system in Alzheimer's disease. Proc Natl Acad Sci U S A 2000;97:9902-9906.   DOI