Several markers of infectious agents have been investigated in people with mental disorders due to their neurological interactions. Any association between these agents and risk of subsequent bipolar disorder remains unclear.

Infectious agents include Toxoplasma gondii and Borna Disease Virus. Toxoplasma gondii is a parasitic protozoa usually hosted by domestic cats and other warm-blooded animals, including humans. Borna Disease Virus is the key causative component of Borna disease, a neurological syndrome primarily affecting animals, but sometimes humans.

What is the evidence for markers of infectious agents in people with bipolar disorder?

Moderate to high quality evidence suggests a small effect of increased markers for Borna disease virus and for Toxoplasma gondii in people with bipolar disorder compared to controls. Increases in Toxoplasma gondii antibodies were particularly apparent in people with bipolar disorder who were under 40 years of age. There were no differences in herpes viruses antibodies between patients and controls.

December 2021

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Exposure to infection is often cited as a risk factor for schizophrenia and has recently been investigated in bipolar disorder. This topic summarises the available evidence for the risk of developing bipolar disorder following exposure to influenza and other infectious agents, both before and after birth. The physiological mechanisms underlying any associations are largely unclear. Please also see the topic in Physical Features on markers for infectious agents in adults with bipolar disorder.

What is the evidence for infectious agents as risk factors for bipolar disorder?

Moderate to low quality evidence suggests a large effect of increased risk of bipolar disorder with exposure to meningitis or tuberculosis in childhood, and a medium-sized effect of lower risk of bipolar disorder with exposure to chicken pox in childhood.

There was a medium to large effect of increased risk of bipolar disorder with exposure to maternal influenza during pregnancy, although when trimesters were analysed separately, the effect remained significant only in the third trimester, and only in one study. There were no associations between risk of bipolar disorder and exposure to maternal urinary tract infections or herpes simplex virus 2.

October 2021

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This topic summarises the available evidence on markers of earlier infection (antibodies) in adults with schizophrenia. Please also see the infectious agents as risk factors topic.

The Herpesviridae are a family of viruses which cause latent, recurring, and sometimes lifelong infections. These include Herpes simplex virus (HHV1 & 2) which causes oral and/or genital herpes; the Varicella Zoster Virus (VZV,HHV3) which causes chicken pox, shingles and rarely, encephalitis; the Epstein-Barr Virus (EBV, HHV4) and Cytomegalovirus (CMV, HHV5) which cause neurological complications; and the Herpes lymphotropic virus (HHV6), which causes roseola (skin rash and fever).

Borna Disease Virus (BDV) is the key causative component of Borna disease, a neurological syndrome primarily affecting animals (particularly horses, cattle, sheep, dogs and cats). However, human infection with BDV has been linked to some psychiatric illnesses through its neurological interactions.

Human Endogenous Retroviruses (HERVs) are fragments of ancient viral infections that became embedded within the germ cells (sperm and eggs), and are passed on to subsequent generations, making up a large proportion of the human genome. HERVs are proposed to have involvement in some autoimmune diseases.

The Human T-lymphotropic virus Type I (HTLV-1) is a human retrovirus that integrates into immune cells and is associated with an increased risk of developing cancers such as adult T-cell leukemia, myeloma, and lymphoma.

The Chlamydiaceae family of bacteria can cause a range of infections in humans, including chlamydia and trachoma (Chlyamydia trachomysis) and pneumonia (Chlamydophila pneumonia, Chlamydophila psittaci).

Toxoplasma gondii is a parasitic protozoa, hosted by domestic cats and other warm-blooded animals including humans. Toxoplasma gondii infection is usually of minor consequence to an adult but can have serious implications for a foetus.

What is the evidence for infectious agents in people with schizophrenia?

Moderate to high quality evidence suggests higher levels of markers for Human Herpesvirus-2 (small effect); Borna Disease Virus (small to medium effect); Human Endogenous Retroviruses (HERV-W: large effect); Chlamydophila pneumoniae and Chlamydophila psittaci (large effects); and Toxoplasma gondii (small to medium effect).

Moderate quality evidence indicates a medium-sized increase in antibodies to Toxoplasma gondii in people with recent-onset schizophrenia, and a small increase in antibodies to Toxoplasma gondii prior to illness onset.

October 2020

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Increased exposure to infections prior to the onset of schizophrenia has been recognised, which suggests infections may be involved in its aetiology. Potential mechanisms for this association include direct impacts of infections on the brain, immune activation, inflammatory cytokines, and alterations in the gut microbiota. This topic summarises the available evidence for the risk of developing schizophrenia following exposure to infectious agents, both before and after birth. For further information, please also see the maternal illness, infectious agents and immunological changes topics.

What is the evidence for infectious agents as risk factors for schizophrenia?

Moderate to high quality evidence found a small increased risk of schizophrenia in people exposed to childhood infections, particularly central nervous system viral infections. The effect sizes increased with increasing number of hospitalisations and decreased with increasing age of exposure (up to 10 years old).

Moderate quality evidence from prospective cohort studies, but not retrospective case-control studies, showed a small but significant association between gastroenteritis exposure and later development of schizophrenia. There was also a small increase in Toxoplasma gondii antibodies found before the development of schizophrenia. Toxoplasma gondii is a parasitic protozoa, hosted by domestic cats and other warm-blooded animals, including humans.

Moderate to high quality evidence suggests a small increased risk of psychotic disorders (mostly schizophrenia spectrum or non-affective psychosis) following exposure to herpes simplex type 2 in utero. Lower quality evidence suggests exposure to toxoplasma gondii or genitourinary infections in utero may also be associated with increased risk of psychotic disorders. No significant risk was found following exposure to herpes simplex type 1, influenza (in any trimester), or cytomegalovirus in utero.

April 2022

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