Viral Hypothesis Of Schizophrenia Research Articles

A commentary revisiting the viral hypothesis of schizophrenia: Onset of a schizophreniform disorder subsequent to SARS CoV-2 infection

The viral hypothesis for schizophrenia has persisted for decades, initially supported by observed increases in psychoses subsequent to the influenza pandemic of the early twentieth century, and then later by evidence of elevated viral antibody titres particularly in schizophrenia patient populations. Several research studies have also focused on maternal infections during the second trimester of pregnancy and their long-term effects on fetal brain development, ultimately leading to schizophrenia. No specific virus has been implicated although a handful have received increasing attention. The current pandemic spreading the SARS CoV-2 corona virus world-wide is now showing anecdotal evidence of psychoses newly developing post viral exposure, implicating neuronal inflammation in crucial areas of the brain that could initiate psychotic symptoms. Time will tell if epidemiological data will, similar to the 1918 influenza pandemic, show that schizophrenia spectrum disorders increase after serious viral infections.

39.3 CAN NEUROVIRAL INFECTIONS WITH HERPES SIMPLEX VIRUS, TYPE 1 (HSV-1) CONTRIBUTE TO RDOC?

BackgroundThe ‘viral hypothesis of schizophrenia’ is difficult to prove, partly because it is inherently difficult to find causes for chronic conditions. It is also not easy to date and relate the timing of infections or psychiatric diagnoses. Further, many neuroviruses cannot be isolated from infected persons. Progress could be made using RDoC for cognition as outcomes of infection, since those quantifiable variables cross psychiatric diagnostic domains (as do infections); they can also be monitored longitudinally and assessed with regard to treatment. We have tested this paradigm in relation to Herpes simplex virus, type 1 (HSV-1) that infects over 3.4 billion people. Though it can cause encephalitis, it is asymptomatic in the vast majority, only causing lifelong latent infection in neurons. Over 10 cross-sectional studies and longitudinal studies indicate that even in the absence of overt encephalitis, individuals seropositive for HSV-1 perform significantly worse than seronegative individuals in several cognitive domains, particularly those relating to memory. These associations remain significant following adjustment for demographic variables, such as socio-economic status. Even though post-mortem studies have been inconclusive, brain imaging studies also indicate gray matter volume reductions in frontotemporal regions in infected individuals, consistent with the cognitive impairment. Many neuronal models of latency are also available.MethodsIn a prospective naturalistic follow up sample (PNFU), temporal changes in cognitive functions were analyzed in relation to baseline HSV-1 infection in persons with or without schizophrenia (N=226). Separately, in a randomized controlled trial (RCT), HSV-1 infected, clinically stabilized outpatients with SZ received Valacyclovir (VAL, an antiviral, 1.5 G twice daily for 16 weeks) or placebo (PLA) added to standard antipsychotic treatment, using a stratified randomization design, following placebo run-in (N=67). In both samples, HSV-1 infection (seropositivity) was estimated using serum IgG antibodies. All clinical evaluations were blinded to HSV-1 or treatment. Standardized Z scores for accuracy on eight cognitive domains were analyzed for temporal trajectories using generalized linear models (PNFU) and VAL/PLA differences compared with intent to treat analyses (RCT).ResultsPNFU: At baseline, HSV-1 infected participants had significantly lower accuracy scores for Emotion Identification and Discrimination (EMOD), Spatial memory and Spatial ability (p=0.025, 0.029, 0.046, respectively), regardless of SZ diagnosis. They also had a significantly steeper temporal worsening for EMOD (p=0.03). RCT: EMOD improved significantly in VAL-treated patients (p=0.048, Cohen’s d=0.43).DiscussionHSV-1 infection is associated with time-related dysfunction in EMOD, which indexes social cognition. Conversely, VAL treatment improves EMOD. A portion of HSV-1 associated cognitive dysfunction is progressive, but remediable. Viral infections could be used to investigate and validate RDoC criteria.

Season of birth and inflammatory response system in schizophrenia

Infective agents (e.g., viruses) together with functional alterations of the immune system have been hypothesized to be implicated in the multifactorial pathogenesis of schizophrenia. The viral hypothesis of schizophrenia has been supported by the observation of birth peaks in winter seasons, prenatal exposure to virus epidemics and specific geographic patterns. On the other hand, not all the data published have shown consistent results supporting the immune hypothesis. Thus, it is likely that immune response factors may play a role in the pathogenesis of the disease only in specific subgroups of patients. The aim of the study was to investigate for the presence of differences of IL-6, IL-6R, gp130 and CC16 among four groups of chronic schizophrenic patients categorized according to the season of birth. We hypothesized that patients born in winter and spring would have had increased values of these cytokines. No significant differences were found among the four groups in any of the measures considered. These preliminary results appear to exclude a major role of the season of birth in determining reported interleukins system alterations in chronic schizophrenia.

Estudio ultraestructural del lóbulo temporal y de la sangre periférica en pacientes esquizofrénicos

In spite of the human, social and economic impact of schizophrenia and to be considered a disease of organic origin by several evidences, there are relatively few studies about this disease using electron microscopic techniques.For 23 years we made studies about the viral hypothesis of schizophrenia by means of this technique. We studied limbic structure samples from young adult s dead schizophrenic patients, from fetuses of schizophrenic mothers and from chicken embryos experimentally inoculated with cerebrospinal fluid from schizophrenic patients. In the last ten years we have performed studies of blood and cerebrospinal fluid samples from young schizophrenic patients. We have found some alterations with the same characteristic to those observed in the central nervous system, which are compatible with: a) the viral hypothesis and b) with herpes simplex hominis type I virus, when immuno electronmicroscopic techniques were made.The results obtained in this work can constitute a new element favoring the possible viral etiology of this disease.

The Viral Hypothesis of Schizophrenia*

The Viral Hypothesis of Schizophrenia*