Perioperative neurocognitive dysfunction: thinking from the gut?

With the aging of the world population, and improvements in medical and health technologies, there are increasing numbers of elderly patients undergoing anaesthesia and surgery. Perioperative neurocognitive dysfunction has gradually attracted increasing attention from academics. Very recently, 6 well-known journals jointly recommended that the term perioperative neurocognitive dysfunction (defined according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition) should be adopted to improve the quality and consistency of academic communications. Perioperative neurocognitive dysfunction currently includes preoperatively diagnosed cognitive decline, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction. Increasing evidence shows that the gut microbiota plays a pivotal role in neuropsychiatric diseases, and in central nervous system functions via the microbiota-gut-brain axis. We recently reported that abnormalities in the composition of the gut microbiota might underlie the mechanisms of postoperative cognitive dysfunction and postoperative delirium, suggesting a critical role for the gut microbiota in perioperative neurocognitive dysfunction. This article therefore reviewed recent findings on the linkage between the gut microbiota and the underlying mechanisms of perioperative neurocognitive dysfunction.

Correlates of psychiatric morbidity in typhoid fever in a Nigerian general hospital setting.

This study explored factors associated with psychiatric morbidity in typhoid fever in a Nigerian general hospital. Information such as sociodemographic characteristics, symptom manifestations, results of investigations, neuropsychiatric symptoms, outcome and disposal were obtained from the case files of patients admitted for typhoid fever over a period of six years. The patients with psychiatric morbidity conspicuous enough to be documented by the attending physicians-mostly internists-were compared with those with no documented psychiatric morbidity on sociodemographic and clinical indices. Of the 136 cases, 26 (19.1%) had psychiatric morbidity. This included delirium (73.1%), generalized anxiety disorder (3.8%), depressive episode (3.8%), schizophrenia like disorder (3.8%) and monosymptomatic neuropychiatric manifestations such as apathy, hallucinations and irrelevant talking (15.5%). The clinical and sociodemographic indices that were significantly associated with psychiatric morbidity were diarrhea, blood biochemical imbalance and age (P<.05). Adolescents and young adults were more predisposed to developing psychiatric complications. Some factors potentially associated with psychiatric morbidity in typhoid fever have been identified. There is the need to prospectively assess the burden from psychiatric morbidity and identify interventions that may reduce it.

Association between central nervous system infections during childhood and adult onset schizophrenia and other psychoses: a 28-year follow-up.

BACKGROUND: Maternal exposure to influenza epidemics during pregnancy may increase the risk of schizophrenia in the offspring. We investigated the association between central nervous system (CNS) infections defined prospectively up to the age of 14, and later onset of schizophrenia and other psychoses in the 1966 birth cohort in Northern Finland, which covers 96% of all births in the area during that year. METHODS: Data regarding CNS infections were collected 1966-1980. Registered diagnoses of psychoses in 1982-1993 were validated on DSM-III-R criteria. RESULTS: Out of 11,017 subjects, 145 had suffered a CNS infection during childhood, 102 of them a viral infection, 76 had DSM-III-R schizophrenia and 53 some other psychosis. Four cases of schizophrenia had suffered viral CNS infection and two cases of other psychosis bacterial infection. When neurological abnormalities and father's social class were adjusted odds ratio (OR) of schizophrenia after viral CNS infection was 4.8 (95% confidence intervals [CI] : 1.6-14.0); the other significant risk factors being intelligence quotient (IQ) < 85, perinatal brain damage and male sex but not epilepsy. Similarly adjusted OR of other psychoses was 6.9 (95% CI: 1.4-32.8) after bacterial CNS infection; the other significant risk factors being IQ < 85 and severe hearing defect. Two of the live viral infections were caused by Coxsackie B5 during an epidemic in which 16 neonates were infected together. CONCLUSIONS: Central nervous system infections during childhood clearly carried an increased risk of adult onset schizophrenia or other psychoses, viral infections being important for schizophrenia, particularly Coxsackie B5 during the newborn period.

Contagion in schizophrenia: a critique of Crow and Done (1986).

This article discusses the literature on the possible role of viruses in the development of schizophrenia and outlines the evidence that compelled Crow and Done (1986) to reject a horizontal contagion hypothesis (e.g., sibling to sibling transmission). We posit a genetically determined age after which one becomes vulnerable to the illness, rather than a strict age of onset. We also propose an environmentally determined range of resistance to this susceptibility as an alternative conceptualization of the role of inheritance and of viral exposure in the etiology of the disease. The predictions derived from our new model fit the findings of Crow and Done and are consistent with the older literature of possible viral factors, thus reaffirming the horizontal contagion hypothesis.

Are polioviruses a cause of schizophrenia?

Pre-natal infection with polioviruses could contribute to the subsequent development of schizophrenia. The hypothesis draws support from the declining incidence of schizophrenia, the excess of schizophrenic winter births, and the increased rates of schizophrenia among West Indian immigrants. There are parallels with other late sequelae of poliovirus infections. These postulations generate a testable hypothesis of a genetic link between schizophrenia and susceptibility to poliomyelitis.

The continued search for evidence of retroviral infection in schizophrenic patients.

Retroviral infection has been proposed as an etiologic factor in schizophrenia. In an effort to unmask a latent retrovirus, short term cultures of peripheral lymphocytes from 15 schizophrenic subjects and nine normal controls were exposed to ionizing radiation and co-cultured with indicator cells. Reverse transcriptase activity, a marker of retroviral infection, could not be detected in any of the cultures. Our findings are further evidence against a role for retroviral infection in the etiology of schizophrenia.

A re-investigation of the behavioural effects of intracerebral injection in marmosets of cytopathic cerebrospinal fluid from patients with schizophrenia or neurological disease.

In experiments designed to investigate transmission, cerebrospinal fluid (CSF) from patients with schizophrenia or neurological disease (Huntington's disease) which had been found to induce a cytopathic effect (CPE) in human embryonic fibroblast cell culture was injected intracerebrally into common marmosets. Behavioural observations were made on the animals during a period of 2 1/2 years prior to injection and for 2 1/2 years after injection. In an earlier study (Baker et al. 1983 b) we found that animals injected with CPE + ve CSF became progressively more inactive when compared with those injected with non-cytopathic (CPE -ve) CSF from control patients. In the present study we were unable to replicate this finding. No difference in behaviour emerged between animals injected with control CSF and animals injected with CSF from schizophrenics or patients with neurological disease, nor between animals injected with CPE + ve CSF and animals injected with CPE -ve CSF. The numbers of offspring produced and surviving did not differ between the groups. We conclude that the original findings were due to factors unconnected with the nature of the injected material.

Lack of evidence for a role of T-cell-associated retroviruses as an etiology of schizophrenia.

The evidence that schizophrenia may involve infection by a virus (or viruses) has been indirect. The recent discovery, however, of the human retroviruses--human T-cell lymphoma-leukemia virus-I, and II (HTLV-I, -II) and human immunodeficiency virus (HIV)--now also known to affect the central nervous system (CNS), together with the development of new techniques in retrovirology, have made it possible to investigate more directly the role of this class of viruses as an etiology of schizophrenia. In our first effort to screen for the presence of a T-cell lymphotropic virus in schizophrenia, short-term tissue cultures of peripheral lymphocytes from 17 chronic schizophrenic patients and 10 normal controls were established. The cells were cultured in the presence of T-cell growth factor (TCGF, IL-2), and the culture supernatants were tested for the presence of the retroviral enzyme reverse transcriptase. No T-cell-associated reverse transcriptase activity was detected in cultures from patients or normal controls. Therefore, the data do not provide evidence for a role for T-cell lymphotropic retroviruses as an etiology of schizophrenia.

Viruses in human brains: a search for cytomegalovirus and herpes virus 1 DNA in necropsy tissue from normal and neuropsychiatric cases.

DNA was extracted from the brains of patients with Alzheimer-type dementia, schizophrenia, Huntington's chorea and from patients without neurological disease, and examined for the presence of herpes simplex virus type 1 and human cytomegalovirus sequences. By selecting cloned virus DNA fragments which do not hybridize to normal human DNA we were able to achieve a detection level assessed on reconstruction experiments of 1 virus genome per 50 cells. Screening at such sensitivity did not detect virus sequences in the higher CNS, except in cases of encephalitis or immunosuppression. We conclude that, at this level of sensitivity, these viruses cannot be regarded as normal residents of the higher CNS, and at the time of death they do not appear to be associated with these neuropsychiatric conditions.