Pereira José Carlos, Pradella Hallinan Márcia, Alves Rosana Cardoso
Departamento de Pediatria, Faculdade de Medicina de Jundiaí, Jundiaí, São Paulo, Brazil.
Department of Psychobiology, Sleep Division, Universidade Federal de São Paulo (UNIFESP), Brazil.
Med Hypotheses. 2017 Jan;98:69-75. doi: 10.1016/j.mehy.2016.11.020. Epub 2016 Nov 28.
Seasonal affective disorder is defined as recurrent episodes of major depression, mania, or hypomania with seasonal onset and remission. In this class of mood disturbances, a unipolar major depressive disorder known as winter depression is common in populations living in northern latitudes far from the equator. Winter depression repeatedly occurs in the autumn or winter and remits in the spring or summer, and its etiopathogenesis is currently unknown. However, one can surmise that excessive melatonin production during the reduced duration of daily sunlight in the autumn and winter plays a role in its pathophysiology. Melatonin is synthesized from tryptophan within the pineal gland, which is located outside the blood-brain barrier, and overproduction of melatonin may lead to augmented consumption of tryptophan, from which serotonin is synthesized. As tryptophan is captured from the blood and excessively utilized by the pineal gland, tryptophan blood levels may decline; as such, it is more difficult for tryptophan to pass through the blood-brain barrier and reach the serotonergic neurons as the ratio of tryptophan to the other amino acids that compete for the same transporter to enter the brain is diminished. As such, less tryptophan is available for serotonin synthesis. Moreover, melatonin is known to modulate thyrotropin expression in the thyrotrophic cells of the pars tuberalis of the pituitary gland, and overproduction of melatonin in the autumn or winter months may cause excessive signaling in the pars tuberalis, diminishing its release of thyrotropin and resulting in central hypothyroidism. Both conditions reduced serotonin production and central hypothyroidism may cause depression. Furthermore, the excessive synthesis of melatonin during the autumn and winter may negatively affect the expression of neuromedin U in the pars tuberalis, causing an increased appetite, which is common in winter depression patients. The hypersomnia common in winter depressive patients can be ascribed to excessive circulating melatonin, a hormone that increases the propensity for sleep. Furthermore, central hypothyroidism may also increase sleepiness, as it is known that hypothyroid patients usually experience excessive somnolence. In this theoretical article, we also propose studies to evaluate winter depression patients with regard to the necessity, or not, of offering them an increased amount of tryptophan in their diets during the autumn and winter. We also suggest that the administration of triiodothyronine to winter depressive patients may mitigate their central hypothyroidism.
季节性情感障碍被定义为具有季节性发作和缓解的重度抑郁、躁狂或轻躁狂的反复发作。在这类情绪障碍中，一种被称为冬季抑郁的单相重度抑郁症在远离赤道的高纬度地区人群中很常见。冬季抑郁在秋季或冬季反复出现，在春季或夏季缓解，其病因目前尚不清楚。然而，可以推测，在秋冬日照时间缩短期间褪黑素分泌过多在其病理生理过程中起作用。褪黑素由位于血脑屏障之外的松果体中的色氨酸合成，褪黑素分泌过多可能导致色氨酸消耗增加，而血清素是由色氨酸合成的。由于色氨酸从血液中被捕获并被松果体过度利用，血液中的色氨酸水平可能会下降；因此，随着色氨酸与其他竞争同一转运体进入大脑的氨基酸的比例降低，色氨酸更难穿过血脑屏障并到达血清素能神经元。因此，可用于血清素合成的色氨酸减少。此外，已知褪黑素可调节垂体结节部促甲状腺细胞中促甲状腺激素的表达，秋冬季节褪黑素分泌过多可能导致结节部过度信号传导，减少其促甲状腺激素的释放，导致中枢性甲状腺功能减退。血清素生成减少和中枢性甲状腺功能减退这两种情况都可能导致抑郁。此外，秋冬季节褪黑素的过度合成可能会对结节部神经降压素U的表达产生负面影响，导致食欲增加，这在冬季抑郁患者中很常见。冬季抑郁患者常见的嗜睡可归因于循环中的褪黑素过多，褪黑素是一种增加睡眠倾向的激素。此外，中枢性甲状腺功能减退也可能增加嗜睡，因为已知甲状腺功能减退患者通常会过度嗜睡。在这篇理论文章中，我们还提出了一些研究，以评估冬季抑郁患者在秋冬季节饮食中是否有必要增加色氨酸的摄入量。我们还建议给冬季抑郁患者服用三碘甲状腺原氨酸可能会减轻他们的中枢性甲状腺功能减退。
