Sir: We present a case of a woman who had suffered from chronic fatigue syndrome (CFS) for several years and was admitted for an acute psychotic episode. This association has rarely been described. Case report. Ms. A, a 43-year-old mother of 2 children, was admitted in January 2006 with delusion and hallucinations following a period of exacerbated fatigue. She was afraid that her children would be abducted by the devil and tried to protect them. She begged her children not to get near the walls of her house for fear that the devil could erupt from the walls and take them. Ms. A first experienced persistent fatigue 3 years before admission. Prior to this, she had been a very active woman. She had to stop working and was able to participate in only very few activities during the day. She attributed her fatigue to the overwhelming task of educating her hyperkinetic 9-year-old son. She had a depressive episode of several months’ duration 10 years before admission, following an abortion of a pregnancy involving a malformed child. This episode had subsided without relapse. She had infectious mononucleosis 20 years before admission. A polysomnographic test 2 years before admission showed many awakenings interrupting Ms. A's sleep pattern. She was then diagnosed with chronic fatigue syndrome according to the criteria of Holmes1 and Fukuda.2 Antidepressive medication was prescribed; it alleviated the secondary depressive symptoms but had no impact on her fatigue complaint. During Ms. A's hospitalization, her blood analysis results were unremarkable, excluding common organic causes of fatigue. Results of her neurologic examination at admission were normal. Her brain computed tomography (CT) scan showed frontal cortical atrophy, but neuropsychological tests failed to show major cognitive impairments. Olanzapine was prescribed at the dosage of 15 mg/day, and her symptoms gradually subsided. She was discharged 1 month after admission, totally free of her psychotic symptoms. Her neuroleptic treatment was changed to 10 mg of aripiprazole because of excessive weight gain. Aripiprazole was as effective as olanzapine but allowed her to return to her usual weight. The treatment was gradually stopped after 1 year, with no recurrence of psychotic symptoms. The association between CFS and psychosis has rarely been described. We are aware of only 2 other case reports. The first describes a 28-year-old man who developed CFS after mononucleosis and suffered afterward from a manic episode with psychotic characteristics.3 The second case report describes a 22-year-old patient who developed CFS after mononucleosis and was later diagnosed with schizophrenia.4 His CT scan showed diffuse nonspecific atrophy and widening of sulci, especially in the cerebellum and frontal lobes. His condition had rapidly improved with classical neuroleptics and did not seem to relapse afterward. Epstein-Barr virus is clearly associated with the development of CFS,5,6 even if we still do not understand the pathophysiology involved. Several case reports of psychotic episodes following Epstein-Barr virus infection, but without CFS symptoms, have also been described.7–9 Mononucleosis could be responsible both for the development of CFS and for the psychotic disorder, if the Epstein-Barr virus remains latent and is reactivated in times of greater stress or immunologic weakness.10 The frontal atrophy in our patient as well as in the 22-year-old patient described earlier could be a sequela of an Epstein-Barr virus–induced central nervous system insult. Systematic evaluation of psychotic symptoms should be recommended in patients presenting with mononucleosis. Charles Kornreich, M.D., Ph.D. Maya Szombat, M.D. Yun-Marie Vandriette, M.D. Bernard Dan, M.D., Ph.D. Brugmann Hospital, Brussels, Belgium