Elevated Brain-Derived Neurotrophic Factor Levels During Depressive Mixed States
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors.Methods We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured.Results When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00–1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36–8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15–1.43, p<0.001) were significantly associated with DMX positivity.Conclusion BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.
Abstract
Objective Neurotrophin-like brain-derived neurotrophic factor (BDNF) and pro-inflammatory cytokines may modulate the pathophysiology of mood disorders. Although several studies show alterations in these biomarkers during the depressive, manic, and euthymic states of mood disorders, evidence is lacking for those in a mixed state. Therefore, this study aimed to investigate the relationship between the depressive mixed state (DMX) and peripheral neurobiological factors.Methods We enrolled 136 patients with major depressive episodes. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology Self-Report Japanese version (QIDS-SR-J). The severity of DMX was assessed using the self-administered 12-item questionnaire (DMX-12). Categorical screening as DMX-positive (n=54) was determined by a cutoff score of 13 or more in the specific eight symptoms from the DMX-12; the remaining were DMX-negative (n=82). Serum BDNF, tumor necrosis factor-α, highsensitivity C-reactive protein, and interleukin-6 levels were measured.Results When comparing biomarkers between the DMX-positive and DMX-negative groups, higher serum BDNF concentration in the DMX-positive group than in the DMX-negative group was the only significant finding (p=0.009). A positive correlation existed between the total score of the eight specific symptoms of DMX-12 and the BDNF concentration (r=0.190, p=0.027). After adjustment for confounders, logistic regression analysis revealed that BDNF (odds ratio [OR]=1.07, 95% confidence interval [CI]=1.00–1.14, p=0.045), bipolar diagnosis (OR=3.43, 95% CI=1.36–8.66, p=0.009), and total QIDS-SR-J score (OR=1.29, 95% CI=1.15–1.43, p<0.001) were significantly associated with DMX positivity.Conclusion BDNF was positively associated with DMX severity, suggesting that higher BDNF concentrations may be involved in the pathophysiology of DMX.
참고문헌 (33)
- Judd LL, "Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes", J Affect Disord, 138, pp.440~448 (2012)
- Goldberg JF, "Manic symptoms during depressive episodes in 1, 380patients with bipolar disorder : findings from the STEP-BD", Am J Psychiatry, 166, pp.173~181 (2009)
- Koukopoulos A, "Melancholia agitata and mixed depression", Acta Psychiatr Scand Suppl, 115, pp.50~57 (2007)
- Iwanami T, "Psychomotor agitation in major depressive disorder is a predictive factor of mood-switching", J Affect Disord, 170, pp.185~189 (2015)
- Benazzi F, "Defining mixed depression", Prog Neuropsychopharmacol Biol Psychiatry, 32, pp.932~939 (2008)
- American Psychiatric Association, "Diagnostic and statistical manual of mental disorders" (2013), American Psychiatric Association
- Shinzato H, "Development of the 12-item questionnaire for quantitative assessment of depressive mixed state(DMX-12)", Neuropsychiatr Dis Treat, 15, pp.1983~1991 (2019)
- Himmerich H, "Cytokine research in depression : principles, challenges, and open questions", Front Psychiatry, 10, pp.30~ (2019)
- Alesci S, "Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion : clinical implications", J Clin Endocrinol Metab, 90, pp.2522~2530 (2005)
- Osimo EF, "Inflammatory markers in depression : a meta-analysis of mean differences and variability in 5, 166 patients and 5, 083 controls", Brain Behav Immun, 87, pp.901~909 (2020)
- Rowland T, "Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder : systematic review and meta-analyses", Br J Psychiatry, 213, pp.514~525 (2018)
- Shoval G, "The possible role of neurotrophins in the pathogenesis and therapy of schizophrenia", Eur Neuropsychopharmacol, 15, pp.319~329 (2005)
- Sapolsky RM, "Depression, antidepressants, and the shrinking hippocampus", Proc Natl Acad Sci U S A, 98, pp.12320~12322 (2001)
- Banasr M, "Cell atrophy and loss in depression : reversal by antidepressant treatment", Curr Opin Cell Biol, 23, pp.730~737 (2011)
- Piccinni A, "Diurnal variation of plasma brain-derived neurotrophic factor(BDNF)in humans : an analysis of sex differences", Chronobiol Int, 25, pp.819~826 (2008)
- Piccinni A, "Plasma brain-derived neurotrophic factor in treatment-resistant depressed patients receiving electroconvulsive therapy", Eur Neuropsychopharmacol, 19, pp.349~355 (2009)
- Fernandes BS, "Brain-derived neurotrophic factor as a state-marker of mood episodes in bipolar disorders : a systematic review and meta-regression analysis", J Psychiatr Res, 45, pp.995~1004 (2011)
- Luo Y, "Altered serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state of bipolar disorder patients", Psychiatry Res, 244, pp.19~23 (2016)
- Piccinni A, "Decreased plasma levels of brain-derived neurotrophic factor(BDNF)during mixed episodes of bipolar disorder", J Affect Disord, 171, pp.167~170 (2015)
- Shinzato H, "The 12-item self-rating questionnaire for depressive mixed state(DMX-12)for screening of mixed depression and mixed features", Brain Sci, 10, pp.678~ (2020)
- Zamami Y, "Prevalence and profile of depressive mixed state in patients with autism spectrum disorder", Psychiatry Res, 300, pp.113932~ (2021)
- Takeshima M, "Association between the so-called"activation syndrome"and bipolar II disorder, a related disorder, and bipolar suggestive features in outpatients with depression", J Affect Disord, 151, pp.196~202 (2013)
- Azorin JM, "Self-assessment and characteristics of mixed depression in the French national EPIDEP study", J Affect Disord, 143, pp.109~117 (2012)
- Sen S, "Serum brain-derived neurotrophic factor, depression, and antidepressant medications : meta-analyses and implications", Biol Psychiatry, 64, pp.527~532 (2008)
- Molendijk ML, "Serum BDNF concentrations as peripheral manifestations of depression : evidence from a systematic review and meta-analyses on 179associations(N=9484)", Mol Psychiatry, 19, pp.791~800 (2014)
- Munkholm K, "Peripheral blood brain-derived neurotrophic factor in bipolar disorder : a comprehensive systematic review and meta-analysis", Mol Psychiatry, 21, pp.216~228 (2016)
- Lommatzsch M, "The impact of age, weight and gender on BDNF levels in human platelets and plasma", Neurobiol Aging, 26, pp.115~123 (2005)
- Ziegenhorn AA, "Serum neurotrophins--a study on the time course and influencing factors in a large old age sample", Neurobiol Aging, 28, pp.1436~1445 (2007)
- Sun Y, "ProBDNF collapses neurite outgrowth of primary neurons by activating RhoA", PLoS One, 7, pp.e35883~ (2012)
- Zhou L, "Upregulation of blood proBDNF and its receptors in major depression", J Affect Disord, 150, pp.776~784 (2013)
- Munkholm K, "Cytokines in bipolar disorder vs. healthy control subjects : a systematic review and metaanalysis", J Psychiatr Res, 47, pp.1119~1133 (2013)
- Jacoby AS, "Cytokines, brain-derived neurotrophic factor and C-reactive protein in bipolar I disorder-Results from a prospective study", J Affect Disord, 197, pp.167~174 (2016)
- Tuglu C, "Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder", Psychopharmacology(Berl), 170, pp.429~433 (2003)