Link between infections and mental disorders

Link between infections and mental disorders

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Infectious diseases have varying outcomes. Some are common and relatively mild such as the common cold and minor fungal infections. Others are dreaded and deadly. In addition, several studies have suggested a link between infections and mental disorders such as obsessive-compulsive disorders, clinical depression, and schizophrenia, among others.

Infectious diseases and the development of mental disorders

A growing body of studies and a number of researchers and practitioners have collectively explored and discussed the link between infections and mental disorders. Below is a list of these disorders that have been associated or correlated with infectious diseases:

1. Obsessive-Compulsive Disorder and Tic Disorder: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal or PANDAS is a hypothesis that links streptococcal infections with a rapid onset of obsessive-compulsive disorder and/or tic disorder in children.

The study of C. A. Kirvan et al. explained that antibodies from immune response against streptococcal bacterial infection interfere with brain enzyme and basal ganglia functions. This interference disrupts communications between neurons, thus resulting further in a form of obsessive compulsion and tic disorder in children.

A review study by Germana Moretti et al. further mentioned that anti-brain antibodies have been found in a subset of patients with OCD and movement disorders. This same review also mentioned that the mechanism behind PANDAS is similar to the mechanism of rheumatic fever—an autoimmune disease triggered by streptococcal infections.

2. Risk of Developing Depression and Psychosis: There is also a suggested correlation between infections during childhood and the risk of developing clinical depression and/or psychosis in adulthood.

Golam M. Khandaker et al. conducted a population-based, longitudinal study that involved a sample of 4,500 individuals who participated in a prior research called the “Avon Longitudinal Study of Parents and Children” or the “Children of the 90s” program.

Results revealed that higher levels of the systemic inflammatory markers Interleukin 6 or IL-6, a protein released in the blood by the immune system during infection, in childhood are associated with an increased risk of developing depression and psychosis in young adulthood.

Aside from establishing a link between infections and mental disorders, the aforementioned result further suggested that inflammation might explain why there is a high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.

3. Schizophrenia in Later Life: Prenatal infection might also trigger schizophrenia in later life according to suggestions from several studies, that establishing further the general link between infections and mental disorders.

The review study of Alan S. Brown and Elena J. Derkits mentioned that an emerging body of literature from epidemiologic, clinical, and preclinical investigations has provided evidence that gestational exposure to infection contributes to the development of schizophrenia in later life. A popular hypothesis explains that prenatal infection affects normal fetal brain development due to an increase in several cytokines—small proteins that are important in cell signaling.

Intrauterine exposure to high levels of infection-induced cytokines is also associated with chorioamnionitis, periventricular leukomalacia, and cerebral palsy. These brain abnormalities develop because of several mechanisms, including stimulation of microglia, resulting in white matter abnormalities. These same white matter abnormalities have been associated with schizophrenia.

There is also an emerging theory centered on the viral origin of schizophrenia. A synthetic review of studies by M. Leboyer et al. mentioned that patients suffering from schizophrenia have elevated transcription of HERV-W, as well as elements and antigens of HERV-W envelopes and capsid proteins in their blood samples.

HERV-W is a particular type of human endogenous retrovirus or HERV. Another study by Olivia Diem et al. mentioned that HERVs have been associated with several neurological and neuropsychiatric disorders. Apart from HERV-W, transcripts and proteins of other HERV groups such as the ERV9 and HERV-K(HML-2) have been detected in brain samples or cerebrospinal fluid of schizophrenic patients.

Conclusion: How infections might trigger mental disorders?

The exact reason as to why infections might influence the development of mental disorders remains unclear simply because of different mechanisms of action hypothesized and explored by researchers. It is worth mentioning that other studies have also linked infections with the development of cognitive disorders or impairments.

Kirvan et al. provided one plausible reason nonetheless. Their study mentioned that infections prompt an immune response that results in the production of antibodies to neutralize pathogens. As illustrated in a particular strain of streptococcal bacteria, some types of infections caused by specific types of infectious agents result in the production of specific types of antibodies. Some of these antibodies trigger an autoimmune response that attacks specific constituents of the brain and/or nervous system.

It is also possible that the infectious agents themselves directly harm the brain. In the case of prenatal infections, the study of Brown and Derkits explained that this situation affects normal fetal brain development due high levels of infection-induced cytokines.

The HERV hypothesis, as explained by Leboyer et al. and Diem et al., also suggests that infections triggers the transcriptions or expression of genetic retroviral remnants that are imprinted deeply in the human genome. The expression of some of these retroviral remnants might have negative effect on specific constituents of the brain and/or nervous system.

Undeniably, the link between infections and mental disorders are worth acknowledging and further exploring. An editorial published in The Lancet Psychiatry in 2015 said that the growing body of research dedicated to exploring and understanding how infections trigger the development of mental disorders has paved the way for the return of immunopsychiatry. This discipline initially emerged from the field of psychoneuroimmunology during the 20th century and it is currently dedicated to understanding how immune mechanisms govern and influence behaviors and emotions or mental and psychiatric functions.

FURTHER READINGS AND REFERENCES

  • Brown, A. S. & Derkits, E. J. 2010. Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. The American Journal of Psychiatry. 167(3): 261-280. DOI: 10.1176/appi.ajp.2009.09030361
  • Khandaker, G. M., Pearson, R. M., Zammit, S., et al. 2014. Association of serum Interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: A population-based longitudinal study. JAMA Psychiatry. 71(10): 1121-1128. DOI: 10.1001/jamapsychiatry.2014.1332
  • Kirvan, C. A., Swedo, S. E., Snider, L. A., & M. W., Cunningham. 2006. Antibody-mediated neuronal cell signaling in behavior and movement disorders. Journal of Neuroimmunology. 179(1): 173-179. DOI: 10.1016/j.jneuroim.2006.06.017
  • Moretti, G., Pasquini, M., Mandarelli, G., Tarsitani, L., & Biondi, M. 2008. What every psychiatrist should know about PANDAS: A review. Clinical Practice and Epidemiology in Mental Health. 4(13). DOI: 10.1186/1745-0179-4-13
  • The Lancet Psychiatry. 2015. Mind and antibody: The return to immunopsychiatry. The Lancet Psychiatry. 2(3): 191. DOI: 10.1016/S2215-0366(15)00057-7