정신신체의학 (Korean Journal of Psychosomatic Medicine)

한국정신신체의학회 (Korean Psychosomatic Society)
권호 표지
DOI QR코드

DOI QR Code

정신과적 투약력이 없는 초발 주요 우울장애 청소년 환아들에서의 백질 구조적 연결성 감소

Decreased White Matter Structural Connectivity in Psychotropic Drug-Naïve Adolescent Patients with First Onset Major Depressive Disorder

  • 서은수 (고려대학교 구로병원 정신건강의학과 소아청소년 정신의학분과) ;
  • 김지현 (고려대학교 구로병원 신경과) ;
  • 서상일 (고려대학교 구로병원 영상의학과) ;
  • 박소영 (우리아이들병원) ;
  • 이전호 (고려대학교 구로병원 정신건강의학과 소아청소년 정신의학분과) ;
  • 이종하 (고려대학교 구로병원 정신건강의학과 소아청소년 정신의학분과) ;
  • 김인성 (지멘스 헬스케어) ;
  • 이문수 (고려대학교 구로병원 정신건강의학과 소아청소년 정신의학분과)
  • Suh, Eunsoo (Divison of Child and Adolescent Psychiatry, Department of Psychiatry, Korea University Guro Hospital) ;
  • Kim, Jihyun (Department of Neurology, Korea University Guro Hospital) ;
  • Suh, Sangil (Department of Radiology, Korea University Guro Hospital) ;
  • Park, Soyoung (Woorisoa Children's Hospital) ;
  • Lee, Jeonho (Divison of Child and Adolescent Psychiatry, Department of Psychiatry, Korea University Guro Hospital) ;
  • Lee, Jongha (Divison of Child and Adolescent Psychiatry, Department of Psychiatry, Korea University Guro Hospital) ;
  • Kim, In-Seong (Simens Health Care) ;
  • Lee, Moon-Soo (Divison of Child and Adolescent Psychiatry, Department of Psychiatry, Korea University Guro Hospital)
  • 투고 : 2017.09.04
  • 심사 : 2017.12.21
  • 발행 : 2017.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

연구목적 최근의 신경영상 연구들은 주요 우울장애의 기전을 인지 회로와 감정 회로 연결의 기능장애 즉, 후외방 전두피질과 전전두엽을 번연계로 연결하는 전측대상피질의 연결성 장애에 초점을 맞추고 있다. 소아청소년 주요 우울장애에서 확산텐서영상(diffusion tensor image, DTI)을 사용한 종전의 연구들은 양측 구상회속, 양측 하측 전두후두속, 좌측 전측대상피질, 좌측 상종속 등에서 신경연결의 감소를 보고하였다. 이 연구에서 우리는 정신과적 투약력이 없는 초발 주요 우울장애 청소년에서의 신경 연결성을 DTI를 이용하여 정상 대조군과 비교하였다. 방 법 고려대학교 구로병원을 내원한 청소년 환아들 중 정신과적 투약력이 없으며 주요 우울장애를 처음으로 진단받은 환아들(n=26, 남성 10명, 여성 16명) 및 대조군(n=27, 남성 5명, 여성 22명)을 모집하였다. 정신과적 면담, 지능지수, 해밀턴 우울척도를 포함한 심리검사, 확산강조영상을 포함한 MRI 검사가 항우울제 투약 전에 시행되었다. Fractional anisotropy(FA), radial diffusivity, mean diffusivity, axial diffusivity가 DTI를 사용하여 계산되었다. 통계적 분석을 위해 FMRIB Software Library-Tract Based Spatial Statistic가 사용되었다. 결 과 전체 뇌의 분석에서는 유의한 구조적 변화를 관찰할 수 없었다. 그러나 관심영역을 지정하여 시행한 분석을 하였을 때, 환아군에서 대조군에 비해 우측 상종속 부위에 유의미한 FA값의 감소를 보인 3개의 다발이 관찰되었다. 결 론 주요 우울장애를 진단받은 청소년 환아군에서 대조군에 비해 DTI에 기반하여 우측의 상종속에 연결성 감소를 보였다. 따라서 DTI를 통한 구조적 연결성은 정신과적 투약력이 없는 초발 주요 우울장애 청소년에서도 생체 표지자로 사용될 수 있을 것이라 생각된다.

Objectives : Recent neuroimaging studies focus on dysfunctions in connectivity between cognitive circuits and emotional circuits: anterior cingulate cortex that connects dorsolateral orbitofrontal cortex and prefrontal cortex to limbic system. Previous studies on pediatric depression using DTI have reported decreased neural connectivity in several brain regions, including the amygdala, anterior cingulate cortex, superior longitudinal fasciculus. We compared the neural connectivity of psychotropic drug naïve adolescent patients with a first onset of major depressive episode with healthy controls using DTI. Methods : Adolescent psychotropic drug naïve patients(n=26, 10 men, 16 women; age range, 13-18 years) who visited the Korea University Guro Hospital and were diagnosed with first onset major depressive disorder were registered. Healthy controls(n=27, 5 males, 22 females; age range, 12-17 years) were recruited. Psychiatric interviews, complete psychometrics including IQ and HAM-D, MRI including diffusion weighted image acquisition were conducted prior to antidepressant administration to the patients. Fractional anisotropy(FA), radial, mean, and axial diffusivity were estimated using DTI. FMRIB Software Library-Tract Based Spatial Statistics was used for statistical analysis. Results : We did not observe any significant difference in whole brain analysis. However, ROI analysis on right superior longitudinal fasciculus resulted in 3 clusters with significant decrease of FA in patients group. Conclusions : The patients with adolescent major depressive disorder showed statistically significant FA decrease in the DTI-based structure compared with healthy control. Therefore we suppose DTI can be used as a bio-marker in psychotropic drug-naïve adolescent patients with first onset major depressive disorder.

키워드

참고문헌

  1. Merikangas KR, He JP, Burstein M, Swanson SA, Avenevoli S, Cui L, Benjet C, Georgiades K, Swendsen J. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication--Adolescent Supplement(NCS-A). J Am Acad Child Adolesc Psychiatry 2010;49:980-989. https://doi.org/10.1016/j.jaac.2010.05.017
  2. Bang KS, Chae SM, Hyun MS, Nam HK, Kim JS, Park KH. The mediating effects of perceived parental teasing on relations of body mass index to depression and self-perception of physical appearance and global self-worth in children. J Adv Nurs 2012;68:2646-2653. https://doi.org/10.1111/j.1365-2648.2012.05963.x
  3. Avenevoli S, Stolar M, Li J, Dierker L, Ries Merikangas K. Comorbidity of depression in children and adolescents: models and evidence from a prospective high-risk family study. Biol Psychiatry 2001;49:1071-1081. https://doi.org/10.1016/S0006-3223(01)01142-8
  4. Kessler RC, Avenevoli S, McLaughlin KA, Green JG, Lakoma MD, Petukhova M, Pine DS, Sampson NA, Zaslavsky AM, Merikangas KR. Lifetime co-morbidity of DSM-IV disorders in the US National Comorbidity Survey Replication Adolescent Supplement(NCS-A). Psychol Med 2012;42:1997-2010. https://doi.org/10.1017/S0033291712000025
  5. Rohde P, Lewinsohn PM, Klein DN, Seeley JR, Gau JM. Key Characteristics of Major Depressive Disorder Occurring in Childhood, Adolescence, Emerging Adulthood, Adulthood. Clin Psychol Sci 2013;1.
  6. SAMHSA Center for Behavioral Health Statistics Quality USoA. Suicidal Thoughts Among Youths Aged 12 to 17 with Major Depressive Episode;2005.
  7. Zisook S, Lesser I, Stewart JW, Wisniewski SR, Balasubramani GK, Fava M, Gilmer WS, Dresselhaus TR, Thase ME, Nierenberg AA, Trivedi MH, Rush AJ. Effect of age at onset on the course of major depressive disorder. Am J Psychiatry 2007;164:1539-1546. https://doi.org/10.1176/appi.ajp.2007.06101757
  8. Paus T, Keshavan M, Giedd JN. Why do many psychiatric disorders emerge during adolescence? Nat Rev Neurosci 2008;9:947-957. https://doi.org/10.1038/nrn2513
  9. Boes AD, McCormick LM, Coryell WH, Nopoulos P. Rostral anterior cingulate cortex volume correlates with depressed mood in normal healthy children. Biol Psychiatry 2008;63:391-397. https://doi.org/10.1016/j.biopsych.2007.07.018
  10. Steingard RJ, Renshaw PF, Hennen J, Lenox M, Cintron CB, Young AD, Connor DF, Au TH, Yurgelun-Todd DA. Smaller frontal lobe white matter volumes in depressed adolescents. Biol Psychiatry 2002;52:413-417. https://doi.org/10.1016/S0006-3223(02)01393-8
  11. Peterson BS, Warner V, Bansal R, Zhu H, Hao X, Liu J, Durkin K, Adams PB, Wickramaratne P, Weissman MM. Cortical thinning in persons at increased familial risk for major depression. Proc Natl Acad Sci U S A 2009;106:6273-6278. https://doi.org/10.1073/pnas.0805311106
  12. Cascio CJ, Gerig G, Piven J. Diffusion tensor imaging: Application to the study of the developing brain. J Am Acad Child Adolesc Psychiatry 2007;46:213-223. https://doi.org/10.1097/01.chi.0000246064.93200.e8
  13. Sexton CE, Mackay CE, Ebmeier KP. A systematic review of diffusion tensor imaging studies in affective disorders. Biol Psychiatry 2009;66:814-823. https://doi.org/10.1016/j.biopsych.2009.05.024
  14. Jiang J, Zhao YJ, Hu XY, Du MY, Chen ZQ, Wu M, Li KM, Zhu HY, Kumar P, Gong QY. Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging. J Psychiatry Neurosci 2016;42:150-163.
  15. Cullen KR, Klimes-Dougan B, Muetzel R, Mueller BA, Camchong J, Houri A, Kurma S, Lim KO. Altered white matter microstructure in adolescents with major depression: a preliminary study. J Am Acad Child Adolesc Psychiatry 2010;49:173-183.
  16. LeWinn KZ, Connolly CG, Wu J, Drahos M, Hoeft F, Ho TC, Simmons AN, Yang TT. White matter correlates of adolescent depression: structural evidence for frontolimbic disconnectivity. J Am Acad Child Adolesc Psychiatry 2014;53:899-909. https://doi.org/10.1016/j.jaac.2014.04.021
  17. Essau CA. Course and outcome of major depressive disorder in non-referred adolescents. J Affect Disord 2007;99:191-201. https://doi.org/10.1016/j.jad.2006.09.010
  18. Yi JS, Bae SO, Ahn YM, Park DB, Noh KS, Shin HK, Woo HW, Lee HS, Han SI, Kim YS. Validity and Reliability of the Korean Version of the Hamilton Depression Rating Scale (K-HDRS). J Korean Neuropsychiatr Assoc 2005; 44:456-465.
  19. Kim YS, Cheon KA, Kim BN, Chang SA, Yoo HJ, Kim JW, et al. The reliability and validity of Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean version(K-SADS-PL-K). Yonsei Med J 2004;45:81-89. https://doi.org/10.3349/ymj.2004.45.1.81
  20. Cho SC, Lee YS. Development of the Korean form of the Kovacs' Childeren's Depression Inventory. Journal of the Korean Neuropsychiatric Association 1990;29:943-956.
  21. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004;23 Suppl 1:S208-S219. https://doi.org/10.1016/j.neuroimage.2004.07.051
  22. Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TE. Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 2006;31:1487-1505. https://doi.org/10.1016/j.neuroimage.2006.02.024
  23. Pizzagalli DA. Frontocingulate dysfunction in depression: toward biomarkers of treatment response. Neuropsychopharmacology 2011;36:183-206. https://doi.org/10.1038/npp.2010.166
  24. Videbech P. PET measurements of brain glucose metabolism and blood flow in major depressive disorder: a critical review. Acta Psychiatr Scand 2000;101:11-20.
  25. Tymofiyeva O, Connolly CG, Ho TC, Sacchet MD, Henje Blom E, LeWinn KZ, Xu D, Yang TT. DTI-based connectome analysis of adolescents with major depressive disorder reveals hypoconnectivity of the right caudate. J Affect Disord 2017;207:18-25. https://doi.org/10.1016/j.jad.2016.09.013
  26. Hueston CM, Cryan JF, Nolan YM. Stress and adolescent hippocampal neurogenesis: diet and exercise as cognitive modulators. Transl Psychiatry 2017;7:e1081. https://doi.org/10.1038/tp.2017.48
  27. Guo W, Liu F, Xun G, Hu M, Guo X, Xiao C, Chen H, Chen J, Zhao J. Disrupted white matter integrity in first-episode, drug-naive, late-onset depression. J Affect Disord 2014;163:70-75. https://doi.org/10.1016/j.jad.2014.03.044
  28. Liu X, Watanabe K, Kakeda S, Yoshimura R, Abe O, Ide S, et al. Relationship between white matter integrity and serum cortisol levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics. Br J Psychiatry 2016;208:585-590. https://doi.org/10.1192/bjp.bp.114.155689
  29. Cheng Y, Xu J, Yu H, Nie B, Li N, Luo C, et al. Delineation of early and later adult onset depression by diffusion tensor imaging. PLoS One 2014;9:e112307. https://doi.org/10.1371/journal.pone.0112307