Coronavirus immunoreactivity in individuals with a recent onset of psychotic symptoms.

Prenatal influenza exposure increases the risk for schizophrenia and brings to question how other respiratory viruses may contribute to neuropsychiatric disease etiopathology. Human coronaviruses cause respiratory infections that range in seriousness from common colds to severe acute respiratory syndrome. Like influenza, coronaviruses can be neurotropic. To test for associations between coronaviruses and serious mental disorders, we utilized a recently developed assay and measured immunoglobulin G (IgG) response against 4 human coronavirus strains (229E, HKU1, NL63, and OC43) in 106 patients with a recent onset of psychotic symptoms and 196 nonpsychiatric controls. We expressed results quantitatively as antibody levels and qualitatively as seroprevalence relative to a defined seropositivity cutoff value. Patient IgG levels were higher than controls for HKU1, NL63, and OC43, with HKU1 and NL63 both showing highly significant patient-to-control differences (HKU1, P ≤ .002; NL63, P ≤ .00001). All 4 coronaviruses were more seroprevalent in patients vs controls, with greatest intergroup differences observed for HKU1 (93% vs 77%, P ≤ .0001). HKU1 and NL63 associations with the patient group were further supported by multivariate analyses that controlled for age, gender, race, socioeconomic status, and smoking status (HKU1, odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.03-1.67, P ≤ .027; NL63, OR = 2.42, 95% CI = 1.25-4.66, P ≤ .008). Among patients, NL63 was associated with schizophrenia-spectrum (OR = 3.10, 95% CI = 1.27-7.58, P ≤ .013) but not mood disorders. HKU1 and NL63 coronavirus exposures may represent comorbid risk factors in neuropsychiatric disease. Future studies should explore links between the timing of coronavirus infections and subsequent development of schizophrenia and other disorders with psychotic symptoms.

A double-blind trial of adjunctive allopurinol for schizophrenia.

OBJECTIVE: To investigate if adjunctive allopurinol reduces symptoms in schizophrenia outpatients with persistent symptoms despite adequate pharmacotherapy. METHOD: N=59 schizophrenia outpatients were randomly assigned to receive adjunctive allopurinol 300 mg bid or identical-looking placebo for 8 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly. RESULTS: A total of n=51 patients completed the trial. Including all n=59 randomized patients, a total of 4 of 31 in the allopurinol group and 0 of 28 in the placebo group had at least a 20% reduction in total PANSS score at the final study visit (chi-square=3.88, p=.049). Among the n=51 completers, individuals in the allopurinol group rated themselves as more improved than did those in the placebo group (z=-2.24, p=.025). The allopurinol medication was well tolerated and there were not any adverse events attributed to the study medication. CONCLUSIONS: Allopurinol may be an effective adjunctive medication for some patients with persistent schizophrenia.

Double blind trial of adjunctive valacyclovir in individuals with schizophrenia who are seropositive for cytomegalovirus.

OBJECTIVE: To investigate if adjunctive valacyclovir, an antiviral medication, reduces symptoms of persistent schizophrenia in individuals who are seropositive for cytomegalovirus (CMV). METHOD: N=47 CMV seropositive schizophrenia outpatients were randomly assigned to receive valacyclovir 1 g twice daily (n=24) or placebo (n=23) for 16 weeks after a 2-week placebo run-in. Symptoms were assessed biweekly. RESULTS: There was no significant difference in the change of positive, negative, general, or total PANSS symptoms between the valacyclovir vs. the placebo group. CONCLUSIONS: The study did not demonstrate benefit of adjunctive valacyclovir for schizophrenia individuals with persistent symptoms who are CMV seropositive.

Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes.

Nicotine addiction is prevalent in individuals with schizophrenia. Nicotine activation of nicotinic receptors (nAChRs) is time- and dose-dependent, but gene expression analyses often rely on qualitative self- or family-reported measures of smoking. We sought lymphocyte surrogates for cerebral alpha7-nAChR activity and tested if receptor transcription correlated with concurrently measured serum biomarkers for smoking [cotinine, C-reactive protein (CRP)]. PCR surveys to detect lymphocytic alpha7-related isoforms identified CHRFAM7A as the only consistently amplifiable transcript. In 20 smoking-matched people (n = 10 schizophrenia, n = 10 controls), we found significantly lower CHRFAM7A in cotinine and self-reported smokers versus nonsmokers (p

Development of a nucleocapsid-based human coronavirus immunoassay and estimates of individuals exposed to coronavirus in a U.S. metropolitan population.

Coronaviruses cause respiratory infections ranging from common colds to severe acute respiratory syndrome (SARS) in humans. Estimates for exposure to non-SARS coronaviruses are high, particularly for 229E and OC43; however, less information regarding seroprevalence is available for HKU1 and NL63. To measure exposure rates to these four coronavirus strains (229E, HKU1, NL63, and OC43), we devised an immunoassay based on amino- and carboxy-terminally tagged recombinant coronavirus nucleocapsid antigens. Four human and one feline coronavirus antigen were cloned into baculoviruses expressed in insect cells and recovered proteins bound in the solid phase of an enzyme-linked immunosorbent assay-based system. We screened sera from 10 children and 196 adults and established primary cutoff points based on immunoglobulin G (IgG) antibody levels of the predominantly seronegative children. The proportion of seropositive adults for each coronavirus was as follows: 229E, 91.3%; HKU1, 59.2%; NL63, 91.8%; and OC43, 90.8%. No evidence of a significant serological response to the feline coronavirus was observed. Significant associations of coronavirus seropositivity and antibody levels with age, gender, race, socioeconomic status, smoking status, and season of the blood draw were tested with chi-square and regression analyses. The group II coronaviruses (OC43 and HKU1) were significantly associated with race (P

Predictors of occupational status six months after hospitalization in persons with a recent onset of psychosis.

Participation in work or school activity is an important aspect of social functioning in individuals with a recent onset of psychosis. We measured the predictors of occupational status 6 months following hospitalization in a sample of 71 adults with recent onset affective or non-affective psychosis. At baseline, participants were evaluated with cognitive measures including the Wisconsin Card Sorting Test, symptom rating scales, the Modified Vocational Index to assess occupational status, and other clinical and demographic measures. At follow-up, occupational status was re-assessed and categorized as whether or not the patient had any current work or school activity. Results of a backwards stepwise logistic regression examining occupational status at follow-up yielded a significant model with the following independent predictors: a higher baseline level of cognitive functioning as measured by performance on the Wisconsin Card Sorting Test lower level of baseline depression as measured by the Calgary Depression Scale; and better socioeconomic status as measured by level of maternal education. Cognitive functioning, but not psychosis severity, is a significant independent predictor of occupational status early in the course of psychotic illness.

Polymorphisms in human endogenous retrovirus K-18 and risk of type 2 diabetes in individuals with schizophrenia.

Type 2 diabetes is a major health problem in individuals with schizophrenia. The genetic basis of diabetes risk in individuals with schizophrenia has not been previously defined. We measured polymorphisms in a human endogenous retrovirus, Herv K-18, which is located in the CD48 signaling lymphocyte activating (SLAM) gene on chromosome 1. The study population consisted of 229 individuals with schizophrenia, 29 of whom had a history of type 2 diabetes, as well as 136 control individuals without a history of a psychiatric disorder or type 2 diabetes. We found that a haplotype defined by 2 polymorphisms in the envelope region of Herv K-18 is highly associated with type 2 diabetes in a population of 229 individuals with schizophrenia, with an odds ratio of 9.0 (95% confidence limits 2.3-34.7, p<.001) adjusted for race, gender and type of antipsychotic medication. Lower levels of association were found in other polymorphisms located in the 3'untranslated region of Herv K-18 and in adjacent loci in CD48. Polymorphisms in endogenous retroviruses which are located near immunomodulatory genes may constitute risk factors for diabetes in individuals with schizophrenia.

Association between cognitive functioning, exposure to Herpes Simplex Virus type 1, and the COMT Val158Met genetic polymorphism in adults without a psychiatric disorder.

Previous studies have documented that serologic evidence of infection with the neurotropic human herpesvirus Herpes Simplex Virus type 1 (HSV-1) is associated with increased levels of cognitive dysfunction in individuals with schizophrenia or bipolar disorder. The catechol-o-methyl transferase (COMT) Val158Met polymorphism has also been associated with cognitive dysfunction in individuals with psychiatric disorders as well as in some control populations. We examined whether these factors are independently associated with cognitive functioning in adults without a history of a psychiatric disorder. A total of 240 individuals were evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Wisconsin Card Sorting Test (WCST). We measured IgG antibodies to HSV-1 by enzyme immunoassay and employed real time PCR to measure COMT Val158Met genotypes. Serological evidence of HSV-1 was significantly associated with a lower RBANS total score independent of demographic factors and the COMT Val158Met genotype. The strongest association between cognitive functioning and serological evidence of HSV-1 infection was with the domain of delayed memory. Serological evidence of HSV-1 infection was associated with an 18-fold increased odds of having a severe impairment in this domain. The Val/Val genotype of the COMT Val158Met polymorphism was also significantly associated with the RBANS total score and with a moderate decrease in the domain of attention. Infections with HSV-1 and the COMT Val158Val genotype are risk factors for cognitive deficits in non-elderly persons without a psychiatric disorder.

The catechol O-methyltransferase Val158Met polymorphism is not associated with broad-based cognitive functioning in schizophrenia.

BACKGROUND: A valine/methionine polymorphism of the catechol O-methyltransferase gene at the nucleotide which encodes amino acid val or met at position 158 in the protein (COMT Val158Met polymorphism) has been associated with deficits in executive functioning in schizophrenia in some studies. The association between the COMT polymorphism and other cognitive domains has been the focus of only limited investigation. METHODS: We measured COMT Val158Met genotypes in N=364 individuals with schizophrenia. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We employed univariate and multivariate analyses of variance to determine the association between COMT genotypes and the RBANS index and individual test scores. RESULTS: There was no significant association between the COMT Val158Met genotypes and any of the RBANS index or individual test scores measured in either univariate or multivariate analyses (all p>.3). CONCLUSION: Based on the results in our sample, the catechol O-methyltransferase Val158Met polymorphism is not associated with broad-based cognitive functioning in schizophrenia.

The association between cognitive functioning and occupational status in persons with a recent onset of psychosis.

The ability to engage in occupational activity is an important aspect of functioning in individuals with recent onset psychosis. We measured the determinants of occupational status in a sample of n = 86 adults with a recent onset of affective or nonaffective psychosis. Participants were evaluated with the Repeatable Battery of Neuropsychological Status, the Wisconsin Card Sorting Test, symptom rating scales, and other clinical and demographic measures. Results of a discriminant function analysis indicated that the most significant differences between those who worked or attended school and those who did not could be attributed to better immediate verbal memory (F = 13.16, p < .0005) and the absence of substance abuse (F = 5.17, p = .026). Occupational activity was not significantly associated with age, gender, race, or symptom severity in this population. Cognitive assessments may prove useful to identify recent onset patients who are most at risk for occupational impairment and who could most benefit from therapeutic interventions.