Editorial

Abstract

There is a long-standing belief that viral infections can cause depressive illness [1]. Early crosssectional studies of patients with depressive disorders supported an association with raised antibody titers against herpes simplex virus, [2] but studies of larger numbers of patients found no association with antibodies to herpes simplex [3], influenza [4], or neurotropic viruses [5]. Influenza may be associated with depression [6] but no prospective study has been reported to confirm this [7]. There are several reports of depressive illness following other, mainly viral, infections [6,7], including the human immunodeficiency virus [8]. Reports of depression after infectious mononucleosis (IM) span half a century. In 1948 Isaacs [9] reported 206 patients with clinical IM. A quarter of the patients complained of weakness, sweating, dizziness, depression, and nervousness 3 months and longer after the infection. In their study of 300 patients with Paul-Bunnell test-positive IM, Prick and De Sonnaville [10] reported that “psychical deviations occurring most frequently were weakness of concentration, forgetfulness, mental tiredness and depressive dissatisfaction.” Pitts et al. [11] have even suggested that the Epstein-Barr virus (EBV) is the cause of idiopathic depressive illness, finding an association with elevated or more frequent EBV early antigen (EA) antibodies. DeLisi et al. [12,13] also found high EA antibody levels in patients with major depressive illness, but found the same association with schizophrenia, and suggested that the association was nonspecific. Amsterdam et al. [14] were unable to confirm these findings in a controlled study of 26 drug-free patients with major depressive disorder. Glaser et al. [15] suggest that any association between distress and EBV antibodies may be related to the immunological effects of stress rather than being specific to depressive illness. The clinical illness of infectious mononucleosis, or glandular fever, was first described by Pfeiffer in Germany in 1889 (“Drusenfieber”) [16]. The illness is usually a self-limiting lymphoproliferative infectious disease, most commonly caused by the Epstein-Barr virus [17]. The normal prognosis is recovery and return to normal activities within 4–6 weeks [18]. Elevated hepatocellular enzyme concentrations occur in at least 85% of cases, but are usually back to normal levels by 5 weeks [19]. Gross neurological complications of IM, most commonly meningitis [20], occur in 1%–5% of cases. Minor brain complications are quite common following IM. Pejme [21] found that 27% of 162 patients with clinical IM had cerebrospinal fluid cell counts above 5 per cubic mm and 32% had diffuse slowing and occasional focal abnormalities on the electroencephalogram. Severe depressive illness has been reported after IM [22]. Cadie et al. [23] reported that 13 out of 20 women retrospectively reported significant depression and anxiety in the year following IM, but there was no excess morbidity in men. In a more recent retrospective case control study, depression was found to be a significantly more frequent complaint after IM than after an ordinary upper respiratory tract infection (URTI) [24]. We do not know whether these mood states were clinically significant, or how long they lasted. Until now, there have been no published prospective studies of the incidence or prognosis of psychiatric illnesses or distress following IM. Katon et al. [25] (in this issue of General Hospital Psychiatry) report a prospective primary care (HMO) study of 150 patients with acute IM. Using a standardized psychiatric interview, they found that only 7% had a DSM III-R psychiatric disorder some 2 weeks after onset. The large majority (5% of the whole sample) had a major depressive episode. Although there was no comparison group, the authors point out that this prevalence is similar to that found in the general population. They followed up subjects for 6 months after onset, with a question-