We report a case of Hashimoto encephalopathy initially presented as a drug-resistant depression with predominant apathy and asthenia, successfully treated with cyclophosphamide. We suspected that the psychiatric symptoms were due to a deficit in neurotransmitter synthesis related to immune activation. We hypothesized that the immunomodulatory treatment helped to restore the neurotransmitter synthesis and thus decreased the patient’s depressive symptoms. In this case report we propose an innovative model in which immunity might disturbs neurotransmitters synthesis leading to depressive symptoms.