Repetitive transcranial magnetic stimulation in the treatment of resistant depression: changes of specific neurotransmitter precursor amino acids

被引:21
作者
Leblhuber, F. [1 ]
Geisler, S. [2 ]
Ehrlich, D. [1 ]
Steiner, K. [1 ]
Reibnegger, G. [3 ]
Fuchs, Dietmar [2 ]
Kurz, K. [4 ]
机构
[1] Kepler Univ Clin, Dept Gerontol, Linz, Austria
[2] Innsbruck Med Univ, Bioctr, Inst Biol Chem, Innrain 80,Room M04-313, A-6020 Innsbruck, Austria
[3] Graz Med Univ, Otto Loewi Res Ctr, Div Physiol Chem, Graz, Austria
[4] Innsbruck Med Univ, Dept Internal Med, Innsbruck, Austria
关键词
Treatment-resistant depression; Transcranial magnetic stimulation; Phenylalanine; Tyrosine; Phenylalanine hydroxylase; TRYPTOPHAN DEGRADATION; PREFRONTAL CORTEX; OXIDATIVE STRESS; THETA-BURST; PHENYLALANINE; MECHANISMS; KYNURENINE; TYROSINE; RTMS;
D O I
10.1007/s00702-021-02363-7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression offers an alternative therapy, since more than every third patient is not responding to adequate antidepressive treatment. In this interventional study safety, symptom development and changes of serum concentrations of neurotransmitter precursor amino acids, of immune activation and inflammation markers, of brain-derived neurotrophic factor (BDNF), nitrite as well as of salivary amylase were measured before and after a frontal polar cortex stimulation using rTMS as add-on treatment in 38 patients with treatment-resistant depression. Out of these, 17 patients received sham stimulation as a control. Treatment was well tolerated: with the exception of one patient of the verum group, who described discomfort during the second treatment, no serious adverse effects were observed. Improvement of depression with a significant decrease in the HAMD-7 scale (p = 0.001) was found in patients treated with rTMS, but not in sham-treated patients. Furthermore, serum phenylalanine and tyrosine dropped significantly (p = 0.03 and p = 0.027, respectively) in rTMS-treated patients. The kynurenine to tryptophan ratio (Kyn/Trp) tended to decrease under rTMS (p = 0.07). In addition, associations between concentrations of BDNF and neopterin as well as serum nitrite levels were found in patients after rTMS treatment, which indicates an influence of immune regulatory circuits on BDNF levels. In the sham-treated patients, no changes of biomarker concentrations were observed. Results show that rTMS is effective in the treatment of resistant depression. rTMS appears to influence the enzyme phenylalanine hydroxylase, which plays a central role in the biosynthesis of neurotransmitter precursors tyrosine and dihydroxyphenylalanine (DOPA).
引用
收藏
页码:1225 / 1231
页数:7
相关论文
共 44 条
[1]   RECOVERY FROM DEPRESSION AFTER ELECTROCONVULSIVE-THERAPY IS ACCOMPANIED BY EVIDENCE OF INCREASED TETRAHYDROBIOPTERIN-DEPENDENT HYDROXYLATION [J].
ANDERSON, DN ;
WILKINSON, AM ;
ABOUSALEH, MT ;
BLAIR, JA .
ACTA PSYCHIATRICA SCANDINAVICA, 1994, 90 (01) :10-13
[2]   Are EMG and visual observation comparable in determining resting motor threshold? A reexamination after twenty years [J].
Badran, Bashar W. ;
Ly, Martina ;
DeVries, William H. ;
Glusman, Chloe E. ;
Willis, Angela ;
Pridmore, Saxby ;
George, Mark S. .
BRAIN STIMULATION, 2019, 12 (02) :364-366
[3]   rTMS of the Dorsomedial Prefrontal Cortex for Major Depression: Safety, Tolerability, Effectiveness, and Outcome Predictors for 10 Hz Versus Intermittent Theta-burst Stimulation [J].
Bakker, Nathan ;
Shahab, Saba ;
Giacobbe, Peter ;
Blumberger, Daniel M. ;
Daskalakis, Zafiris J. ;
Kennedy, Sidney H. ;
Downar, Jonathan .
BRAIN STIMULATION, 2015, 8 (02) :208-215
[4]   Neuroinflammation in Bipolar Depression [J].
Benedetti, Francesco ;
Aggio, Veronica ;
Pratesi, Maria Luisa ;
Greco, Giacomo ;
Furlan, Roberto .
FRONTIERS IN PSYCHIATRY, 2020, 11
[5]   Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial [J].
Blumberger, Daniel M. ;
Vila-Rodriguez, Fidel ;
Thorpe, Kevin E. ;
Feffer, Kfir ;
Noda, Yoshihiro ;
Giacobbe, Peter ;
Knyahnytska, Yuliya ;
Kennedy, Sidney H. ;
Lam, Raymond W. ;
Daskalakis, Zafiris J. ;
Downar, Jonathan .
LANCET, 2018, 391 (10131) :1683-1692
[6]   Chronic Low-Grade Inflammation in Elderly Persons Is Associated with Altered Tryptophan and Tyrosine Metabolism: Role in Neuropsychiatric Symptoms [J].
Capuron, Lucile ;
Schroecksnadel, Sebastian ;
Feart, Catherine ;
Aubert, Agnes ;
Higueret, Denise ;
Barberger-Gateau, Pascale ;
Laye, Sophie ;
Fuchs, Dietmar .
BIOLOGICAL PSYCHIATRY, 2011, 70 (02) :175-182
[7]  
Connolly K Ryan, 2012, J Clin Psychiatry, V73, pe567, DOI 10.4088/JCP.11m07413
[8]   Introduction - Cytokines and depression: An update [J].
Dantzer, R ;
Wollman, EE ;
Yirmiya, R .
BRAIN BEHAVIOR AND IMMUNITY, 2002, 16 (05) :501-502
[9]   Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments [J].
Duman, Ronald S. ;
Sanacora, Gerard ;
Krystal, John H. .
NEURON, 2019, 102 (01) :75-90
[10]   Diagnosis and definition of treatment-resistant depression [J].
Fava, M .
BIOLOGICAL PSYCHIATRY, 2003, 53 (08) :649-659