Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder

Biol Psychiatry. 2004 Mar 15;55(6):588-93. doi: 10.1016/j.biopsych.2003.10.008.


Background: In a previous investigation, we found an association between reduced cognitive functioning and the prevalence of antibodies to herpes simplex virus type 1 in individuals with schizophrenia. The current study was undertaken to determine if this association also occurs in individuals with bipolar disorder.

Methods: Cognitive functioning and serologic evidence of infection with potentially neurotropic herpesviruses were measured in 117 individuals with bipolar disorder and in 100 individuals without a history of psychiatric disorder. Cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status. For each patient, serologic evidence of infection was ascertained by the measurement of serum immunoglobulin G class antibodies with specificities for six potentially neurotropic human herpesviruses. The association between serologic evidence of herpesvirus infection and cognitive functioning was analyzed by univariate analyses, as well as multivariate analyses that included demographic and clinical factors associated with cognitive functioning.

Results: Serologic evidence of infection with herpes simplex virus type 1 was an independent predictor of decreased cognitive functioning in the individuals with bipolar disorder (F = 20.5, p <.0001). Discriminant function analysis indicated that most of the difference in cognitive functioning between individuals who were antibody positive and antibody negative for herpes simplex virus type 1 could be attributed to immediate verbal memory (F = 12.07, p <.001). There was no significant association between cognitive functioning and the other human herpesviruses. No association between antibodies to herpesviruses and cognitive functioning was found in the control individuals without a history of psychiatric disorder.

Conclusions: Serologic evidence of herpes simplex virus type 1 infection is associated with cognitive impairment in individuals with bipolar disorder.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Antibodies, Viral / analysis
  • Bipolar Disorder / complications*
  • Bipolar Disorder / immunology
  • Bipolar Disorder / virology
  • Cognition Disorders / etiology*
  • Cognition Disorders / immunology
  • Cognition Disorders / virology
  • Cohort Studies
  • Female
  • Herpesviridae Infections / complications*
  • Herpesvirus 1, Human* / immunology
  • Herpesvirus 1, Human* / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests / statistics & numerical data
  • Prevalence
  • Psychiatric Status Rating Scales / statistics & numerical data


  • Antibodies, Viral