SEROTONERGIC ABNORMALITIES IN SEASONAL AFFECTIVE DISORDER AND LIGHT THERAPY

我们先前的研究表明，5-羟色胺能功能参与了 季节性情感障碍的病理生理学及发病机制 光疗法的作用。5-羟色胺激动剂m-CPP已经产生 未经治疗的SAD患者(PTS)过度兴奋和兴奋 对m-CPP的激素反应异常。 5-羟色胺-1受体激动剂伊帕西酮和5-羟色胺拮抗剂美特灵 与预测相反，SAD症状有所减少。今年我们：a)赠送 美特戈林研究中的睡眠记录；B)检查m-CPP对 正电子发射断层扫描(PET)的5-羟色胺能功能 讨论5-羟色胺相关候选基因之间的可能关系 到SAD和偏头痛。 A)我们的美特高林研究的睡眠结果表明没有显著的 美特灵对所研究的任何睡眠参数的影响。那里 是光疗的效果。在光疗过程中，PTS显示出一种趋势 接近较晚的睡眠开始，较早的睡眠偏移量和中点，减少 持续时间，午睡时间减少的趋势，以及总睡眠时间的减少。 这些发现再次证实了强光对 睡在PTS里。B)鉴于我们早先对m-CPP的调查结果，我们试图 评估m-CPP是否也引起大脑代谢的变化。我们 寻求复制早期PET发现，显示前额叶增加 眼眶前额代谢率降低。我们试图复制更早的 报道了m-CPP诱导的激活欣快感。PTS和CTS输液 使用m-CPP和安慰剂&在每次输液后进行PET扫描。血样 提取ACTH、皮质醇和催乳素以及雌二醇的样本， 女性孕酮、卵泡刺激素和黄体生成素&男性卵泡刺激素、卵泡刺激素和黄体生成素 睾丸激素。采用NIMH25项自评量表进行测评 激活和欣快感。在行为上，我们再次复制了之前的 PTS和CTS中5-羟色胺相关候选基因的发现在过去 去年，我们培育了新的细胞系，用于添加PTS和CTS。这些 更多的细胞系正在等待分析和与临床的关联 侧写。我们发现了5HT2C受体基因的一个变种 约占CTS的14%。该变体似乎具有功能性 在青蛙卵母细胞中的意义。我们计划测试它的功能意义 在人类中，通过给CTS注射m-CPP，带有和不带有变种& 测量各种与5-羟色胺相关的依赖指标。D)最后， 我们开始了一项关于偏头痛可能遗传基础的研究 灵感来自：a)偏头痛的强大家族基础；b) 偏头痛和情绪障碍的一致性；&c)证据表明 5-羟色胺能紊乱与偏头痛有关。到目前为止，我们有 为32名偏头痛患者建立了细胞系。数据分析是 即将到来。

Our prior research suggests that serotonergic function is involved in the pathophysiology of seasonal affective disorder (SAD) & the mechanism of action of light therapy. The serotonin agonist m-CPP has produced exaggerated activation & euphoria in untreated SAD patients (PTS), & abnormal hormonal responses have occurred in response to m-CPP & to the 5HT-1A agonist ipsapirone; & metergoline, a serotonin antagonist, though contrary to prediction, reduced SAD symptoms. This year we: A) present sleep log from the metergoline study; B) examine the effects of m-CPP on serotonergic function using positron emission tomography (PET); & D) discuss possible relationships of serotonin-related candidate genes both to SAD & migraine headaches. A) Sleep results from our metergoline study indicated no significant effects of metergoline upon any of the sleep parameters studied. There were effects of light therapy. During light therapy PTS showed a trend towards later sleep onsets, earlier sleep offsets & midpoints, decreased duration, a trend toward decreased nap time, & reduced total sleep time. These findings again conform the powerful effects of bright light on sleep in PTS. B) Given our earlier findings with m-CPP, we sought to assess whether m-CPP also induces changes in cerebral metabolism. We sought to replicate an earlier PET finding showing increased prefrontal & decreased orbitofrontal metabolism. We sought to replicate an earlier reported m-CPP-induced activation - euphoria. PTS & CTS were infused with m-CPP & placebo & administered a PET scan after each infusion. Blood samples for ACTH, cortisol & prolactin were drawn, as well as estradiol, progesterone, FSH and LH for females & on males for FSH, LH & testosterone. The NIMH 25-item self-rating scale was used to measure activation & euphoria. Behaviorally, we again replicated our earlier finding of serotonin-related candidate genes in PTS & CTS. In the past year, we developed new cell lines for addition PTS & CTS. These additional cell lines now await analysis & correlation with clinical profile. We identified a variant of the 5HT2C receptor gene in approximately 14% of CTS. The variant appears to have functional significance in frog oocytes. We plan to test its functional significance in humans by administering m-CPP to CTS with & without the variant & measure a variety of serotonin-related dependent measures. D) Finally, we began a study of the possible genetic basis of migraine headaches that was inspired by: a) the strong familial basis of migraines; b) concordance of migraines & mood disorders; & c) evidence which suggest that serotonergic disturbances are involved in migraines. To date we have established cell lines for 32 migraine patients. Data analysis is forthcoming.