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The Nestorian Schism of 431AD to 544AD caused a split between the Christian churches of Sassanid Persia, which were affiliated with Nestorius, and churches that rejected him. The schism rose out of a Christological dispute, the key figures in which were Cyril of Alexandria and Nestorius. Nestorius and the doctrine he was accused of, which emphasized the distinctness between Christ's human and divine natures, were condemned at the First Council of Ephesus in 431 and the Council of Chalcedon. This forced a breach between the Churches which defended Nestorius with the state church of the Roman Empire, thereby causing the Church of the East, the Christian church of Sassanid Persia, to become known as the Nestorian Church for taking the side of Nestorius. Despite ratifying the Council of Chalcedon at the 544 Synod of Mar Aba I, the Christians of the Church of the East have been known most commonly, though inaccurately, as the Nestorians ever since.
The doctrine of Nestorianism is associated with Nestorius, Patriarch of Constantinople 428 – 431. Prior to becoming Patriarch, Nestorius had been a student of Theodore of Mopsuestia at the School of Antioch. Nestorius argued that Christ's human and divine natures were distinct, and was therefore against using the title Theotokos (Mother of God) for the Virgin Mary, instead preferring to call her Christotokos (Mother of Christ). Cyril of Alexandria considered Nestorius' doctrine contrary to Orthodox teaching, and encouraged measures against it. Finally Nestorius and his doctrine were condemned at the First Council of Ephesus in 431, and the finding was reiterated at the Council of Chalcedon in 451.
Afterward churches aligned with Nestorius, centered around the School of Edessa, were separated from the rest of the Christian Church. Anathemized in the Roman Empire, they relocated to Sassanid Persia, where they were welcomed by Persian Christians who had already declared independence of Constantinople in an attempt to cast off accusations of foreign allegiance. The School of Edessa relocated to the Persian city of Nisibis (see School of Nisibis), thereafter a center of Nestorianism. In 484 the Sassanids executed the pro-Byzantine Catholicos Babowai, thus enabling the Nestorian Bishop of Nisibis Barsauma to increase his influence over the bishops of the region and effectively ending links between Persian Christianity and the Roman Empire. Thereafter Nestorianism spread widely through Asia, gaining a presence in India, Central Asia, the Mongol territories, and China. The medieval Nestorian movement survives in the Assyrian Church of the East, practiced most widely in Iran, Iraq, and Syria.