Biomedical subjects

Robert H Yolken

Publications and source records attributed to Robert H Yolken.

At least 19 recordsLinked to original sources

PubMed2007

Antibodies to infectious agents in individuals at ultra-high risk for psychosis.

BACKGROUND: While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis. METHODS: Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures. RESULTS: Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses. CONCLUSIONS: In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.

Adolescent↗

PubMed2006

Neuropsychological functioning in bipolar disorder and schizophrenia.

BACKGROUND: Some patients with bipolar disorder (BD) demonstrate neuropsychological deficits even when stable. However, it remains unclear whether these differ qualitatively from those seen in schizophrenia (SZ). METHODS: We compared the nature and severity of cognitive deficits shown by 106 patients with SZ and 66 patients with BD to 316 healthy adults (NC). All participants completed a cognitive battery with 19 individual measures. After adjusting their test performance for age, sex, race, education, and estimated premorbid IQ, we derived regression-based T-scores for each measure and the six cognitive domains. RESULTS: Both patient groups performed significantly worse than NCs on most (BD) or all (SZ) cognitive tests and domains. The resulting effect sizes ranged from .37 to 1.32 (mean=.97) across tests for SZ patients and from .23 to .87 (mean=.59) for BD patients. The Pearson correlation of these effect sizes was .71 (p<.001). CONCLUSIONS: Patients with bipolar disorder suffer from cognitive deficits that are milder but qualitatively similar to those of patients with schizophrenia. These findings support the notion that schizophrenia and bipolar disorder show greater phenotypic similarity in terms of the nature than severity of their neuropsychological deficits.

Adult↗

PubMed2006

Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis.

Recent studies have linked infectious agents to schizophrenia. The largest number of studies has involved the analysis of Toxoplasma gondii; these studies were subjected to a meta-analysis. Published articles and abstracts were identified by searches of MEDLINE, Ovid, and Google Scholar; by a search of Chinese publications; through letters to researchers; and by visiting China. Published and unpublished controlled studies that used serological methods for measuring T. gondii antibodies to assess inpatients and/or outpatients diagnosed with schizophrenia were selected for analysis, and source documents were translated as needed. Forty-two studies carried out in 17 countries over 5 decades were identified; 23 of these (6 unpublished) met selection criteria. The combined odds ratio (OR) was 2.73 (95% confidence interval, 2.10 to 3.60; chi-square with 1 df 263; P < .000001). Seven studies that included only patients with first-episode schizophrenia (OR 2.54) did not differ significantly from 16 studies that included patients in all clinical phases (OR 2.79). The results suggest that individuals with schizophrenia have an increased prevalence of antibodies to T. gondii. This association is consistent with other epidemiological studies as well as with animal studies. Although the OR of 2.73 is modest, it exceeds that for genetic or other environmental factors identified to date and suggests that Toxoplasma is in some way associated with a large number of cases of schizophrenia. If an etiological association can be proven, it would have implications for the design of measures for the prevention and treatment of this disease.

Animals↗

PubMed2006

Toxoplasma gondii as a risk factor for early-onset schizophrenia: analysis of filter paper blood samples obtained at birth.

BACKGROUND: Infections during fetal life or neonatal period, including infections with Toxoplasma gondii, may be associated with a risk for schizophrenia and other mental disorders. The objectives of this study were to study the association between serological markers for maternal and neonatal infection and the risk for schizophrenia, related psychoses, and affective disorders in a national cohort of newborns. METHODS: This study was a cohort-based, case-control study combining data from national population registers and patient registers and a national neonatal screening biobank in Denmark. Patients included persons born in Denmark in 1981 or later followed up through 1999 with respect to inpatient or outpatient treatment for schizophrenia or related disorders (ICD-10 F2) or affective disorders (ICD-10 F3). RESULTS: Toxoplasma gondii immunoglobulin G (IgG) levels corresponding to the upper quartile among control subjects were significantly associated with schizophrenia risk (odds ratio [OR] = 1.79, p = .045) after adjustment for urbanicity of place of birth, year of birth, gender, and psychiatric diagnoses among first-degree relatives. There was no significant association between any marker of infection and other schizophrenia-like disorders or affective disorders. CONCLUSIONS: Our study supports an association between Toxoplasma gondii and early-onset schizophrenia. Further studies are needed to establish if the association is causal and if it generalizes to cases with onset after age 18.

Animals↗

PubMed2006

Association study of IL10, IL1beta, and IL1RN and schizophrenia using tag SNPs from a comprehensive database: suggestive association with rs16944 at IL1beta.

Genetic association studies of several candidate cytokine genes have been motivated by evidence of immune dysfunction among patients with schizophrenia. Intriguing but inconsistent associations have been reported with polymorphisms of three positional candidate genes, namely IL1beta, IL1RN, and IL10. We used comprehensive sequencing data from the Seattle SNPs database to select tag SNPs that represent all common polymorphisms in the Caucasian population at these loci. Associations with 28 tag SNPs were evaluated in 478 cases and 501 unscreened control individuals, while accounting for population sub-structure using the genomic control method. The samples were also stratified by gender, diagnostic category, and exposure to infectious agents. Significant association was not detected after correcting for multiple comparisons. However, meta-analysis of our data combined with previously published association studies of rs16944 (IL1beta -511) suggests that the C allele confers modest risk for schizophrenia among individuals reporting Caucasian ancestry, but not Asians (Caucasians, n=819 cases, 1292 controls; p=0.0013, OR=1.24, 95% CI 1.09, 1.41).

Adult↗

PubMed2006

Transactivation of elements in the human endogenous retrovirus W family by viral infection.

BACKGROUND: Aberrant expression of human endogenous retrovirus (HERV) elements in the W family has previously been associated with schizophrenia, multiple sclerosis and preeclampsia. Little is know regarding the basal expression, transcriptional regulation and functional significance of individual HERV-elements. Since viral infections have previously been reported to transactivate retroviral long terminal repeat regions we examined the basal expression of HERV-W elements and following infections by influenza A/WSN/33 and Herpes simplex 1 viruses in human cell-lines. METHODS: Relative levels of transcripts encoding HERV-W elements and cellular genes were analyzed by qPCR methods. An analysis of amplicon melting temperatures was used to detect variations in the frequencies of amplicons in discrete ranges of such melting temperatures. These frequency-distributions were taken as proxy markers for the repertoires of transcribed HERV-W elements in the cells. RESULTS: We report cell-specific expression patterns of HERV-W elements during base-line conditions. Expressed elements include those with intact regulatory long terminal repeat regions (LTRs) as well as elements flanked by truncated LTRs. Subsets of HERV-W elements were transactivated by viral infection in the different cell-lines. Transcriptional activation of these elements, including that encoding syncytin, was dependent on viral replication and was not induced by antiviral responses. Serum deprivation of cells induced similar changes in the expression of HERV-W elements suggesting that the observed phenomena are, in part, an effect of cellular stress. CONCLUSION: We found that HERV-W elements, including elements lacking regulatory LTRs, are expressed in cell-specific patterns which can be modulated by environmental influences. This brings into light that mechanisms behind the regulation of expression of HERV-W elements are more complex than previously assumed and suggests biological functions of these transcripts.

Base Sequence↗

PubMed2006

The catechol O-methyltransferase Val158Met polymorphism and herpes simplex virus type 1 infection are risk factors for cognitive impairment in bipolar disorder: additive gene-environmental effects in a complex human psychiatric disorder.

BACKGROUND: Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia. Serological evidence of infection with herpes simplex virus type 1 (HSV-1) has also been identified as a risk factor for cognitive impairment in bipolar disorder. METHODS: We used Taqman technology to measure COMT Val158Met alleles in 107 individuals with bipolar disorder and in 95 controls. We also measured antibodies to HSV-1 in sera obtained from the same individuals. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and the Letter-Number Sequencing Test. The effects of the COMT Val158Met polymorphism and antibodies to HSV-1 on cognitive functioning were analyzed with multinomial logistic regressions. RESULTS: The COMT Val158Val genotype and serological evidence of infection with HSV-1 are independent risk factors for cognitive impairment in individuals with bipolar disorder, particularly in the domains of immediate and delayed memory. Individuals with bipolar disorder with the COMT158 Val/Val genotype and serological evidence of HSV-1 infection were more than 85 times more likely to be in the lowest quintile of cognitive functioning when compared with the highest quintile when controlling for potential confounding variables such as symptom severity and education. Control individuals did not display this association. CONCLUSION: Both the COMT Val158Met polymorphism and serological evidence of HSV-1 infection affect cognitive functioning in individuals with bipolar disorder.

Adult↗

PubMed2006

Cytomegalovirus and schizophrenia.

Several lines of evidence suggest that cytomegalovirus (CMV) may play an aetiological role in schizophrenia. Epidemiologically, both have a worldwide distribution and an increased prevalence in lower socioeconomic groups. Studies have reported that some patients experiencing initial episodes of schizophrenia have increased levels of IgG antibodies against CMV, but not other herpes viruses, in their sera and CSF. Treatment with antipsychotic medications may result in a decrease in CMV antibodies, while treatment with anti-herpes virus and anti-inflammatory medications may reduce symptoms in some individuals with schizophrenia. There is also some overlap in the genes that are thought to operate in CMV infections and schizophrenia. The strongest argument against the role of CMV in schizophrenia is the absence of the traditional CMV neuropathological changes in the brains of individuals with schizophrenia; however, neuropathological studies of CMV have mostly been conducted in immune-compromised individuals. Further studies on CMV and schizophrenia are needed and may lead to improved treatments for schizophrenia.

Antibodies, Viral↗

PubMed2004

Autism and head circumference in the first year of life.

BACKGROUND: It has been reported that children with autism and pervasive developmental disorder have a significantly smaller head circumference at birth and that their head circumference then increases disproportionately rapidly in the first year of life. METHODS: We attempted to replicate these findings using 15 narrowly defined autistic children from the National Collaborative Perinatal Project and approximately 40,000 nonautistic control subjects. RESULTS: The autistic group had a slightly but not significantly larger head circumference at birth. At 4 months, the head circumference in the autistic group was not significantly larger than that of control subjects, but body weight and length were significantly larger in the autistic group. CONCLUSIONS: We believe this is the first report of significant general body growth in autistic children in infancy; the larger head circumference may be part of this excessive general growth.

Age Factors↗

PubMed2004

Cognitive functioning in schizophrenia and bipolar disorder: comparison of performance on the Repeatable Battery for the Assessment of Neuropsychological Status.

Cognitive dysfunction is an important feature of schizophrenia and bipolar disorder. There is uncertainty about the relative magnitude of cognitive deficits in these disorders. We evaluated a total of 446 individuals: 229 with schizophrenia, 117 with bipolar disorder, and 100 controls without a history of psychiatric disorder. All participants were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), a cognitive screening battery that evaluated immediate verbal memory, visuospatial/constructional abilities, attention, language, and delayed memory. A comparison of the three groups showed significant differences on the RBANS total score and all of the measured domains. In all of the comparisons, the schizophrenia group obtained the lowest scores, followed by the bipolar disorder group, and then the individuals without psychiatric disorder. In an analysis of covariance of RBANS total scores with the patient samples, the difference between schizophrenia and bipolar disorder remained significant after controlling for a range of demographic and clinical variables. Both schizophrenia and bipolar disorder are associated with significant cognitive impairments, but those in schizophrenia are more severe. Cognitive deficits may be an appropriate target of treatment interventions in these disorders.

Adult↗

PubMed2004

Infection with herpes simplex virus type 1 is associated with cognitive deficits in bipolar disorder.

BACKGROUND: In a previous investigation, we found an association between reduced cognitive functioning and the prevalence of antibodies to herpes simplex virus type 1 in individuals with schizophrenia. The current study was undertaken to determine if this association also occurs in individuals with bipolar disorder. METHODS: Cognitive functioning and serologic evidence of infection with potentially neurotropic herpesviruses were measured in 117 individuals with bipolar disorder and in 100 individuals without a history of psychiatric disorder. Cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status. For each patient, serologic evidence of infection was ascertained by the measurement of serum immunoglobulin G class antibodies with specificities for six potentially neurotropic human herpesviruses. The association between serologic evidence of herpesvirus infection and cognitive functioning was analyzed by univariate analyses, as well as multivariate analyses that included demographic and clinical factors associated with cognitive functioning. RESULTS: Serologic evidence of infection with herpes simplex virus type 1 was an independent predictor of decreased cognitive functioning in the individuals with bipolar disorder (F = 20.5, p <.0001). Discriminant function analysis indicated that most of the difference in cognitive functioning between individuals who were antibody positive and antibody negative for herpes simplex virus type 1 could be attributed to immediate verbal memory (F = 12.07, p <.001). There was no significant association between cognitive functioning and the other human herpesviruses. No association between antibodies to herpesviruses and cognitive functioning was found in the control individuals without a history of psychiatric disorder. CONCLUSIONS: Serologic evidence of herpes simplex virus type 1 infection is associated with cognitive impairment in individuals with bipolar disorder.

Adolescent↗

PubMed2004

Epigenetic studies of genomic retroelements in major psychosis.

This work is dedicated to the exploration of the role of epigenetic (epiG) factors in major psychosis. One of the key functions of epigenetic modification of the genome of eukaryotic cells is to suppress transcriptional activity of the retroelements. Examples of retroelements are endogenous retroviral sequences (ERVs), Alu's, and LINEs, among others, which as a rule are hypermethylated. There is evidence from schizophrenia (SCH) and other human complex diseases that some of the genomic retroelements become transcribed in the affected tissues. Our goal was to screen DNA samples from post-mortem brain tissues of individuals who were affected with major psychiatric illness for retroelements that were located in the hypomethylated fraction of the genomic DNA. Over 100 Alu sequences were cloned, sequenced, and mapped to the human genome. A substantial portion of the cloned Alu's are located close to or within the genes that may be interesting targets for further genetic, transcription, and epigenetic studies.

Adult↗

PubMed2004

Antibodies to infectious agents in individuals with recent onset schizophrenia.

We investigated the levels of antibodies to infectious agents in the serum and cerebral spinal fluids (CSFs) of individuals with recent onset schizophrenia and compared these levels to those of controls without psychiatric disease. We found that untreated individuals with recent onset schizophrenia had significantly increased levels of serum and CSF IgG antibody to cytomegalovirus and Toxoplasma gondii as compared to controls. The levels of serum IgM class antibodies to these agents were not increased. Untreated individuals with recent onset schizophrenia also had significantly lower levels of serum antibody to human herpesvirus type 6 and varicella zoster virus as compared to controls. Levels of antibodies to herpes simplex virus type 1, herpes simplex virus type 2, and Epstein Barr virus, and did not differ from cases and controls. We also found that treatment status had a major effect on the levels of antibodies in this population. Individuals who were receiving treatment had lower levels of antibodies to cytomegalovirus and Toxoplasma gondii, and higher levels of serum antibodies to human herpesvirus type 6 as compared to untreated individuals. The level of antibodies to Toxoplasma and human herpesvirus type 6 measured in treated individuals did not differ from the levels measured in controls. In the case of cytomegalovirus, the levels of CSF antibodies in treated individuals did not differ from those of controls, while the level of serum IgG antibodies to CMV remained slightly greater than controls in this population. Our studies indicate that untreated individuals with recent onset schizophrenia have altered levels of antibodies to cytomegalovirus, Toxoplasma gondii, and human herpesvirus type 6 while the levels of these antibodies in treated individuals with recent onset schizophrenia are similar to those of controls. These findings indicate that infectious agents may play a role in the etiopathogenesis of some cases of schizophrenia.

Adult↗

PubMed2004

Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia.

Markers of the kynurenine pathway were studied in postmortem frontal cortex obtained from individuals with schizophrenia and controls. Quantitative endpoint RT-PCR was used to measure mRNA transcripts. Of the two enzymes capable of catalyzing the first step in the pathway, tryptophan 2,3-dioxygenase (TDO2) and indoleamine dioxygenase (IDO), the concentration of mRNA for TDO2 was found to be elevated 1.6-fold in the schizophrenia group (P = 0.03), whereas the concentration of the mRNA for IDO was not significantly different between the schizophrenia and control groups. Immunohistochemistry showed an increased density of TDO2-immunopositive astroglial cells in the white matter of patients with schizophrenia (P = 0.04). Neurons and vessels were also immunopositive for TDO2, but there were no significant differences in labeling of these structures between the two groups. These results add to the evidence that kynurenine pathway changes might be involved in the pathogenesis of schizophrenia and the schizophrenia-like psychoses of other disorders.

Adult↗

PubMed2004

Long-term consumption of infant formulas containing live probiotic bacteria: tolerance and safety.

BACKGROUND: Nonpathogenic live bacteria are consumed as food by many children, particularly in the form of yogurt. The tolerance and safety of long-term consumption of specific types and strains of probiotic bacteria are not well documented. OBJECTIVE: The goal was to evaluate tolerance to formulas containing 2 levels of probiotic supplementation and effects on growth, general clinical status, and intestinal health in free-living healthy infants. DESIGN: This was a prospective, double-blind, randomized, placebo-controlled study of healthy infants aged 3-24 mo. Infants were assigned to receive a standard milk-based formula containing 1 x 10(7) colony-forming units (CFU)/g each of Bifidobacterium lactis and Streptococcus thermophilus, formula containing 1 x 10(6) CFU/g each of B. lactis and S. thermophilus, or unsupplemented formula. Clinical outcomes included formula intake, gastrointestinal tolerance, anthropometric measures, daycare attendance, and history of illness. RESULTS: One hundred eighteen infants aged ( +/- SD) 7.0 +/- 2.9 mo at enrollment consumed formula for 210 +/- 127 d. There were no significant differences in age, sex, formula consumption, or length of study between groups. The supplemented formulas were well accepted and were associated with a lower frequency of reported colic or irritability (P < 0.001) and a lower frequency of antibiotic use (P < 0.001) than was the unsupplemented formula. There were no significant differences between groups in growth, health care attention seeking, daycare absenteeism, or other health variables. CONCLUSION: Long-term consumption of formulas supplemented with B. lactis and S. thermophilus was well tolerated and safe and resulted in adequate growth, reduced reporting of colic or irritability, and a lower frequency of antibiotic use.

Bifidobacterium↗

PubMed2004

Association between cognitive functioning and employment status of persons with bipolar disorder.

OBJECTIVE: The purpose of this study was to identify variables associated with employment status among persons with bipolar disorder, including cognitive functioning, severity of symptoms, demographic variables, and variables related to course of illness. METHODS: The authors assessed the current employment status of 117 persons with bipolar disorder. Study participants' cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status, the information and letter-number sequencing subtests of the Wechsler Adult Intelligence Scale III, and part A of the Trail Making Test. Symptoms were rated by using the Brief Psychiatric Rating Scale, the Hamilton Depression Scale, and the Young Mania Rating Scale. A stepwise multivariate logistic regression analysis was used to predict employment status. RESULTS: Fifty-one percent of the study participants had no current work activity, 21 percent worked part-time or as volunteers, and 27 percent had full-time competitive employment. Current employment status was significantly associated with cognitive performance, especially immediate verbal memory, total symptom severity, history of psychiatric hospitalization, and maternal education. No association was found between employment status and history of psychotic symptoms, number of years of education, or age at onset of illness. CONCLUSIONS: Vocational programs for persons with bipolar disorder would benefit from inclusion of a formal cognitive assessment to better assess work potential and to study the predictors of work-related outcomes.

Adolescent↗

PubMed2004

Evaluating RNA status for RT-PCR in extracts of postmortem human brain tissue.

Total RNA was extracted from 105 individual postmortem human brain samples representing a range of postmortem conditions. To improve upon parameters currently used to screen for RNA quality, electropherogram patterns generated by the Agilent Bioanalyzer 2100 were compared to the average score in random hexamer-primed reverse transcription real-time PCR for four housekeeping genes in each RNA sample. The ribosomal ratio (28S to 18S) was found to be unrelated to the housekeeping gene score (r = -0.06; P = 0.50), and there was no threshold value in the ratio that could be applied to effectively categorize the RNA degradation. Although the housekeeping gene score correlated significantly with the percentage of area in the electropherogram corresponding to moderate to high molecular weight intact mRNA (r = 0.41; P = 0.0001), the best discriminator was determined to be the ratio of the 18S peak height to the highest peak in the tRNA to 18S rRNA baseline. Applying a lower boundary of 2.12 for the ratio allowed for the screening out of samples with the lowest housekeeping gene scores without excluding better-quality samples. This measure represents a marked improvement over the 28S to 18S ratio, which proved to be a misleading indicator of the state of the mRNA for use in random hexamer-primed reverse transcription PCR.

Base Sequence↗

PubMed2003

Oligodendrocyte dysfunction in schizophrenia and bipolar disorder.

BACKGROUND: Results of array studies have suggested abnormalities in expression of lipid and myelin-related genes in schizophrenia. Here, we investigated oligodendrocyte-specific and myelination-associated gene expression in schizophrenia and bipolar affective disorder. METHODS: We used samples from the Stanley brain collection, consisting of 15 schizophrenia, 15 bipolar affective disorder, and 15 control brains. Indexing-based differential display PCR was done to screen for differences in gene expression in schizophrenia patients versus controls. Results were cross-validated with quantitative PCR, which was also used to investigate expression profiles of 16 other oligodendrocyte and myelin genes in schizophrenia and bipolar disorder. These genes were further investigated with an ongoing microarray analysis. FINDINGS: Results of differential display and quantitative PCR analysis showed a reduction of key oligodendrocyte-related and myelin-related genes in schizophrenia and bipolar patients; expression changes for both disorders showed a high degree of overlap. Microarray results of the same genes investigated by quantitative PCR correlated well overall. INTERPRETATION: Schizophrenia and bipolar brains showed downregulation of key oligodendrocyte and myelination genes, including transcription factors that regulate these genes, compared with control brains. These results lend support to and extend observations from other microarray investigations. Our study also showed similar expression changes to the schizophrenia group in bipolar brains, which thus lends support to the notion that the disorders share common causative and pathophysiological pathways.

Bipolar Disorder↗