Department of Psychiatry and Psychology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Department of Clinical Sciences, Division of Biostatistics, UT Southwestern Medical Center, Dallas, TX, USA.
Brain Stimul. 2014 Mar-Apr;7(2):243-51. doi: 10.1016/j.brs.2013.11.006. Epub 2013 Dec 3.
Research suggests that alterations in gamma-aminobutyric acid receptor functioning have a role in depression. Paired-pulse transcranial magnetic stimulation (TMS) paradigms are noninvasive measures of cortical inhibitory and excitatory circuits.
OBJECTIVE/HYPOTHESIS: The present study examined pretreatment short-interval intracortical inhibition (SICI), long-interval cortical inhibition (LICI), and intracortical facilitation (ICF) in children and adolescents with major depressive disorder who were initiating fluoxetine treatment. The primary objective was to examine the relationship of these measures with subsequent treatment response. It was hypothesized that alterations in pretreatment GABA and glutamate mediated neurotransmission, would be associated with fluoxetine nonresponse.
Sixteen children and adolescents with major depressive disorder underwent paired-pulse TMS testing before beginning fluoxetine treatment. Response was prospectively characterized by scores of 1 or 2 on the Clinical Global Impression Scale and less than 40 on the Children's Depression Rating Scale-Revised after 6 weeks of fluoxetine treatment (20-40 mg/day).
Eight patients responded to treatment. Least-squares mean LICI values were consistently higher bilaterally for treatment nonresponders. Higher LICI values indicate less inhibition and impaired GABAB functioning. There was no significant effect of treatment response on the measures of SICI and ICF.
Our findings suggest that deficits in pretreatment GABAB may be related to fluoxetine nonresponse in depressed youth. This is congruent with prior work demonstrating that GABAB interneurons have serotonergic input and antidepressants modulate GABAB receptors. These findings also show that TMS paradigms have utility in studying the neurophysiology and treatment of childhood mood disorders.
Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder, http://www.clinicaltrials.gov/ct2/show/NCT00896090?term=cortical+excitability+and+inhibition&rank=2, NCT00896090; Sequential Treatment of Pediatric MDD to Increase Remission and Prevent Relapse, http://www.clinicaltrials.gov/ct2/show/NCT00612313?term=Sequential+Treatment+and+MDD&rank=1, NCT00612313.
研究表明，γ-氨基丁酸受体功能的改变与抑郁症有关。成对脉冲经颅磁刺激（TMS）范式是非侵入性的皮质抑制和兴奋回路的测量方法。
目的/假设：本研究检测了开始氟西汀治疗前的儿童和青少年重度抑郁症患者的短间隔皮质内抑制（SICI）、长间隔皮质抑制（LICI）和皮质内易化（ICF）。主要目的是检查这些措施与随后治疗反应的关系。假设预处理 GABA 和谷氨酸介导的神经递质传递的改变将与氟西汀无反应相关。
16 名患有重度抑郁症的儿童和青少年在开始氟西汀治疗前接受了成对脉冲 TMS 测试。通过在氟西汀治疗 6 周后（20-40mg/天）儿童抑郁评定量表修订版（Children's Depression Rating Scale-Revised）评分<40 分和临床总体印象量表（Clinical Global Impression Scale）评分 1 或 2，前瞻性地确定反应。
8 名患者对治疗有反应。治疗无反应者双侧 LICI 值始终较高。较高的 LICI 值表示抑制作用降低和 GABA 功能受损。SICI 和 ICF 测量值的治疗反应无显著影响。
我们的研究结果表明，治疗前 GABAB 功能缺陷可能与抑郁青少年的氟西汀无反应有关。这与先前的研究结果一致，表明 GABA 中间神经元具有血清素能输入，抗抑郁药调节 GABA 受体。这些发现还表明，TMS 范式在研究儿童情绪障碍的神经生理学和治疗方面具有实用性。
儿童和青少年重度抑郁症的皮质兴奋性和抑制性，http://www.clinicaltrials.gov/ct2/show/NCT00896090?term=cortical+excitability+and+inhibition&rank=2，NCT00896090；儿科 MDD 的序贯治疗以增加缓解和预防复发，http://www.clinicaltrials.gov/ct2/show/NCT00612313?term=Sequential+Treatment+and+MDD&rank=1，NCT00612313。
