目前尚未完全理解遗传和环境因素如何准确地导致抑郁症的临床表现。据怀疑,这一过程较为复杂,且与多因素有关。儿童抑郁症的病理生理学并未像成人抑郁症那样得到很好的理解。在儿童人群中进行的研究很少,一些成人的研究结果还没有在儿童抑郁症中得到证明。例如,皮质醇分泌过多、在抑郁成人中的一致发现尚未在抑郁儿童中复制。[11]Rao U, Dahl RE, Ryan ND, et al. The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression. Biol Psychiatry. 1996 Sep 15;40(6):474-84.http://www.ncbi.nlm.nih.gov/pubmed/8879467?tool=bestpractice.com 然而,有证据表明儿童抑郁症中中枢血清素系统出现失调。现已发现青春期前抑郁的儿童皮质醇减弱,但催乳素分泌增加以响应 L-5-羟色氨酸激发。[12]Ryan ND, Birmaher B, Perel JM, et al. Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression: depressed vs normal children. Arch Gen Psychiatry. 1992 Nov;49(11):843-51.http://www.ncbi.nlm.nih.gov/pubmed/1444721?tool=bestpractice.com 现已证明中枢血清素系统失调可能导致受损的压力和情绪反应、减少冲动控制和情绪失调。[13]Byrum CE, Ahearn EP, Krishnan KR. A neuroanatomic model for depression. Prog Neuropsychopharmacol Biol Psychiatry. 1999 Feb;23(2):175-93.http://www.ncbi.nlm.nih.gov/pubmed/10368863?tool=bestpractice.com[14]Mayberg HS. Limbic-cortical dysregulation: a proposed model of depression. J Neuropsychiatry Clin Neurosci. 1997 Summer;9(3):471-81.http://www.ncbi.nlm.nih.gov/pubmed/9276848?tool=bestpractice.com
对成人抑郁症的研究表明,通过多导睡眠检查的几种睡眠异常,包括减少睡眠连续性、减少慢波睡眠、缩短快速动眼期 (rapid eye movement, REM) 延迟和增加 REM 密度。但是对儿童和成人抑郁症的睡眠检查是不一致的。一些研究表明,儿童和青少年住院的抑郁症患者有睡眠持续性障碍和 REM 压力增加(缩短 REM 延迟和增加 REM 睡眠的比例),但在慢波睡眠中没有障碍。[15]Emslie GJ, Rush AJ, Weinberg WA, et al. Children with major depression show reduced rapid eye movement latencies. Arch Gen Psychiatry. 1990 Feb;47(2):119-24.http://www.ncbi.nlm.nih.gov/pubmed/2302025?tool=bestpractice.com[16]Emslie GJ, Rush AJ, Weinberg WA, et al. Sleep EEG features of adolescents with major depression. Biol Psychiatry. 1994 Nov 1;36(9):573-81.http://www.ncbi.nlm.nih.gov/pubmed/7833421?tool=bestpractice.com[17]Lahmeyer HW, Poznanski EO, Bellur SN. EEG sleep in depressed adolescents. Am J Psychiatry. 1983 Sep;140(9):1150-3.http://www.ncbi.nlm.nih.gov/pubmed/6614218?tool=bestpractice.com[18]Dahl RE, Puig-Antich J, Ryan ND, et al. EEG sleep in adolescents with major depression: the role of suicidality and inpatient status. J Affect Disord. 1990 May;19(1):63-75.http://www.ncbi.nlm.nih.gov/pubmed/2140847?tool=bestpractice.com 在门诊患者中,这个结果是不一致的。[19]Armitage R, Hoffmann R, Emslie G, et al. Sleep microarchitecture in childhood and adolescent depression: temporal coherence. Clin EEG Neurosci. 2006 Jan;37(1):1-9.http://www.ncbi.nlm.nih.gov/pubmed/16475478?tool=bestpractice.com[20]Puig-Antich J, Goetz R, Hanlon C, et al. Sleep architecture and REM sleep measures in prepubertal children with major depression: a controlled study. Arch Gen Psychiatry. 1982 Aug;39(8):932-9.http://www.ncbi.nlm.nih.gov/pubmed/7103682?tool=bestpractice.com[21]Goetz RR, Puig-Antich J, Ryan N, et al. Electroencephalographic sleep of adolescents with major depression and normal controls. Arch Gen Psychiatry. 1987 Jan;44(1):61-8.http://www.ncbi.nlm.nih.gov/pubmed/3800585?tool=bestpractice.com
在儿童抑郁症中还表明了动机和奖励神经通路的中断。[22]Forbes EE, Dahl RE. Neural systems of positive affect: relevance to understanding child and adolescent depression? Dev Psychopathol. 2005 Summer;17(3):827-50.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129134/http://www.ncbi.nlm.nih.gov/pubmed/16262994?tool=bestpractice.com 有证据涉及抑郁症病理生理学中的谷氨酸能系统。[23]Maeng S, Zarate CA Jr. The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep. 2007 Dec;9(6):467-74.http://www.ncbi.nlm.nih.gov/pubmed/18221626?tool=bestpractice.com 在有抑郁症风险的青年中增加了皮质醇以预测抑郁症的发病。[24]Owens M, Herbert J, Jones PB, et al. Elevated morning cortisol is a stratified population-level biomarker for major depression in boys only with high depressive symptoms. Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3638-43.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948242/http://www.ncbi.nlm.nih.gov/pubmed/24550453?tool=bestpractice.com 影像学研究发现,在情绪调节、应激反应、动机、行为抑制和抑郁症状表现方面比较重要的多个脑区和通路(例如,杏仁核、前扣带、前额叶皮质)中体积和功能紊乱。[25]Beesdo K, Lau JY, Guyer AE, et al. Common and distinct amygdala-function perturbations in depressed vs anxious adolescents. Arch Gen Psychiatry. 2009 Mar;66(3):275-85.http://www.ncbi.nlm.nih.gov/pubmed/19255377?tool=bestpractice.com[26]Forbes EE, Christopher May J, Siegle GJ, et al. Reward-related decision-making in pediatric major depressive disorder: an fMRI study. J Child Psychol Psychiatry. 2006 Oct;47(10):1031-40.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2129133/http://www.ncbi.nlm.nih.gov/pubmed/17073982?tool=bestpractice.com[27]Steingard RJ, Yurgelun-Todd DA, Hennen J, et al. Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy. Biol Psychiatry. 2000 Dec 1;48(11):1053-61.http://www.ncbi.nlm.nih.gov/pubmed/11094138?tool=bestpractice.com[28]Rosenberg DR, Mirza Y, Russell A, et al. Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry. 2004 Sep;43(9):1146-53.http://www.ncbi.nlm.nih.gov/pubmed/15322418?tool=bestpractice.com