Clinical Neuroimaging Laboratory, Department of Anatomy, Clinical Science Institute, National University of Ireland Galway, Galway, Ireland.
Int J Neuropsychopharmacol. 2013 May;16(4):733-43. doi: 10.1017/S1461145712000776. Epub 2012 Sep 6.
The central serotonergic system has been implicated in the pathophysiology of panic disorder (PD) by evidence of abnormally elevated serotonin-turnover, reduced pre- and post-synaptic 5-HT(1A)-receptor sensitivity and binding and clinical improvement during administration of agents that enhance serotonergic transmission. Polymorphisms in genes that putatively influence serotonergic neurotransmission increase the vulnerability for developing PD specifically in males. We tested the hypotheses that serotonin transporter (5-HTT) binding is elevated in PD subjects vs. healthy controls in regions where in vivo evidence exists for both elevated 5-HTT and 5-HT(1A) receptor levels in PD and investigated whether the extent of this difference depends upon gender. Volunteers were out-patients with current PD (n=24) and healthy controls (n=24). The non-displaceable component of 5-HTT binding-potential (BP(ND)) was measured using positron emission tomography and the 5-HTT selective radioligand, [(11)C]DASB. PD severity was assessed using the PD Severity Scale. The 5-HTT-BP(ND) was increased in males with PD relative to male controls in the anterior cingulate cortex (F=8.96, p(FDR)=0.01) and midbrain (F=5.09, p(FDR)=0.03). In contrast, BP(ND) did not differ between females with PD and female controls in any region examined. The finding that 5-HTT-binding is elevated in males but not in females with PD converges with other evidence suggesting that dysfunction within the central serotonergic system exists in PD, and also indicates that such abnormalities are influenced by gender. These findings conceivably may reflect a sexual dimorphism that underlies the greater efficacy of serotonin reuptake inhibitor treatment in females vs. males with PD.
中枢 5-羟色胺能系统在惊恐障碍（PD）的病理生理学中起作用，其证据为异常升高的 5-羟色胺转化率、降低的 5-HT1A 受体的前突触和后突触敏感性和结合，以及增强 5-羟色胺传递的药物治疗期间的临床改善。推测影响 5-羟色胺能神经传递的基因多态性增加了 PD 特别是男性发病的易感性。我们检验了以下假设：在 PD 患者和健康对照者中，在有体内证据表明 5-HTT 和 5-HT1A 受体水平升高的区域中，5-HTT 结合升高；并研究了这种差异的程度是否取决于性别。志愿者为门诊 PD 患者（n=24）和健康对照者（n=24）。使用正电子发射断层扫描和 5-HTT 选择性放射性配体[11C]DASB 测量 5-HTT 结合势（BP（ND））的不可置换成分。使用 PD 严重程度量表评估 PD 严重程度。与男性健康对照组相比，男性 PD 患者的前扣带回皮质（F=8.96，p（FDR）=0.01）和中脑（F=5.09，p（FDR）=0.03）中 5-HTT-BP（ND）升高。相比之下，PD 女性与健康对照女性之间在任何检查区域均无 BP（ND）差异。5-HTT 结合在 PD 男性中升高而在 PD 女性中不升高的发现与其他证据一致，表明中枢 5-羟色胺能系统的功能障碍存在于 PD 中，也表明这种异常受性别影响。这些发现可能反映了基础性别二态性，这可能是与 PD 女性相比，SSRIs 治疗在男性中更有效的原因。
