Is there a relationship between influenza and schizophrenia

is there a relationship between influenza and schizophrenia

The study indicated that Flu during the first trimester of pregnancy increased risk of I think is the strongest evidence to date linking (prenatal) influenza exposure However, because the mechanism underlying the schizophrenia connection is (Research); Maternal infections and subsequent psychosis among offspring. There was no increased risk of schizophrenia with influenza during the second or .. There was no association between SSD riskand influenza exposure in the. Human epidemiological studies highlight a direct association between infections during the first trimester of pregnancy and schizophrenia. Infectious agents.

is there a relationship between influenza and schizophrenia

Schizophrenia, maternal influenza virus infection, G protein-coupled receptors GPCRserotonin 5-HT2A receptor, metabotropic glutamate receptors, hallucinogenic drugs LSD Introduction Maternal infection with a variety of agents, such as influenza virus, rubella virus, herpes simplex virus, and poliovirus, has been associated with development of schizophrenia in the adult offspring Brown and Derkits, ; Pearce, ; Patterson, ; Yudofsky, In preclinical research, the influenza virus is among the most widely used models to study the effects of prenatal viral infection on brain development Patterson, ; Meyer et al.

The offspring of mothers infected with mouse-adapted influenza virus display a series of behavioral abnormalities that are relevant to schizophrenia Shi et al.

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As yet, the biochemical changes underlying the behavioral abnormalities induced by maternal viral infection are not definitely established. The human psychoactive effects of drugs such as lysergic acid diethylamide LSD and phencyclidine PCP share several features with schizophrenia, including changes in time and sensory perception, alterations in thought, speech, mood and affect Geyer and Vollenweider, ; Gonzalez-Maeso and Sealfon, It has been demonstrated that the serotonin 5-HT2A receptor is necessary for the effects of hallucinogenic drugs, such as LSD, mescaline and psilocybin, in both murine and human model systems Vollenweider et al.

Indeed, LSD effects were one of the earliest models of schizophrenia Keeler,and are currently believed to model the symptoms that occur at the onset of this disorder Geyer and Vollenweider, The effect of maternal viral infection on the level of expression and behavioral function of 5-HT2A and mGlu2 receptors remains unknown. The natural hosts for influenza viruses are avian species, and a limited number of influenza virus subtypes infect mammalian species including humans Palese, ; Bouvier and Palese, Although mice are not natural hosts for influenza virus, following an intranasal inoculation they develop an illness that closely resembles the disease in humans.

In humans, influenza virus replication is typically restricted to the respiratory track. Being aware of the differences in the primary target tissue for influenza virus infection in mouse and human Li et al.

is there a relationship between influenza and schizophrenia

Virus titers were measured by plaque assay on MDCK cells. All experiments with live virus were carried out under biosafey level 2 BSL-2 containment. Human epidemiological studies highlight a direct association between infections during the first trimester of pregnancy and schizophrenia. Using a much more sophisticated database i. About one-half have replicated the finding, and about one-half have not. These failures to replicate could be due to inaccurate information on infection or other factors, or they may represent true findings of no association between maternal influenza and schizophrenia in some populations.

is there a relationship between influenza and schizophrenia

Interestingly, increased rates of diagnosis for major affective disorder have also been reported following exposure to an influenza epidemic during the second trimester, 4 indicating that effects may not be specific for schizophrenia. In addition to influenza, a wide variety of other maternal infections during pregnancy have been reported to be associated with increased risk for schizophrenia.

  • Maternal infection during pregnancy and schizophrenia
  • Serologic Evidence of Prenatal Influenza in the Etiology of Schizophrenia
  • Schizophrenia and 1957 Pandemic of Influenza: Meta-analysis

These include maternal infections with other viruses measles, rubella, varicella-zoster, polio as well as maternal bronchopneumonia which is largely bacterialmaternal infection with the parasite causing toxoplasmosis and infections of the maternal genital and reproductive systems. More recently, some laboratories have attempted to confirm maternal infection more precisely by analyzing antibodies for viral infection in maternal serum that had been stored from 30 to 40 years until offspring had grown and developed schizophrenia.

As can be appreciated, these are very challenging studies with limits in the sample size due to limited availability of stored serum, questions about storage and stability of samples, etc. Interestingly, while earlier epidemiologic studies had quite consistently implicated influenza in the second trimester of pregnancy, Brown and colleagues' studies with archived maternal serum have implicated the first third to half of pregnancy.

It has been pointed out that, if the association between maternal influenza and schizophrenia holds, then maternal influenza could account for an appreciable amount of the population-associable risk for schizophrenia because influenza is so prevalent. Clearly, these important studies require replication and confirmation.

Other studies examining serologically confirmed maternal infection are those published by Buka and colleagues from the US National Collaborative Perinatal Project. It was noted that the effect sizes for these associations were comparable in magnitude to those reported for some genetic polymorphisms linked to schizophrenia.

is there a relationship between influenza and schizophrenia

However, by contrast, Brown and colleagues found no significant association between seropositivity for HSV-2 in late pregnancy maternal serum and risk for schizophrenia spectrum disorders in offspring in their sample population.

If maternal infection is a risk factor for schizophrenia, it is also evident that the epidemiologic studies have not yet clearly defined which stage of pregnancy might be the main vulnerability period. Both the first and second trimesters have been implicated.

Of course, maternal infection during pregnancy is not thought to be the sole cause of schizophrenia but is speculated to act in interaction with other etiologic factors.

For example, the effects of prenatal infection on fetal neurodevelopment may be exaggerated in those with a particular genetic vulnerability.

As another example, patients with schizophrenia who were exposed to second trimester influenza have been reported to be more likely to have experienced a subsequent obstetric complication and to have had a lower birth weight, compared with patients who did not have second trimester exposure.

These studies have modelled maternal infection either using live influenza viruses or using viral RNA mimics or bacterial endotoxin to produce more controlled infections.

Maternal infection during pregnancy and schizophrenia

Overall, a large number of studies have now demonstrated that, in rodents, maternal infection during pregnancy can indeed produce changes in central nervous system CNS structure, function and behaviour in offspring. These changes include many relevant to schizophrenia, such as deficits in prepulse inhibition of startle, latent inhibition, memory and social interaction; increases in amphetamine-and MK—induced locomotion; alterations in CNS levels of dopamine and tyrosine hydroxylase; and cell death, cell atrophy or reduced volume in the hippocampus.

is there a relationship between influenza and schizophrenia

Although the overall conclusion from these studies supports the idea that maternal infection can alter brain development, as in many fields, each laboratory works with its own particular model, precluding across-laboratory replication of specific findings. The mean weighted RR for subjects who were in their first, second, or third trimester of prenatal life during the pandemic 8 effect sizes was 0.

The pooled results of the type B and type C studies were also negative. The basis to support the hypothesis, however, is controversial. An influential study from Finland, published inreported an increased proportion of schizophrenia diagnoses in patients whose second trimester of fetal life overlapped with the influenza pandemic. Subjects are considered to be exposed if they are born in a given period after an epidemic or pandemic. A more sophisticated method of documenting exposure is the assessment of influenza antibodies in pregnant mothers.

The only study to compare antibody titers in pregnancies giving rise to affected and unaffected offspring involved an American cohort born during the period —, ie, not exposed to the pandemic.

Thus, a correct interpretation of the ecological investigations remains important for an evaluation of the influenza hypothesis. Because this method leads to 9 statistical tests, some associations will emerge by chance. - Schizophrenia Causes and Prevention, prenatal infection

We reasoned that if maternal influenza contributes to the etiology of schizophrenia, a pandemic should increase the risk for those in utero. We therefore performed a meta-analysis to examine whether birth during the 9-month period after the pandemic, or maternal reports of influenza during pregnancy at the time of the pandemic, were risk factors for schizophrenia in the child. Methods Data Sources We performed a MEDLINE search to March using the key words influenza, pandemic, psychosis, schizophrenia, and paranoid, and reviewed the reference lists of relevant articles.