Violence and schizophrenia.
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Commitment of Persons with Psychiatric Disorders↗
Biomedical subjects
E Fuller Torrey
Publications and source records attributed to E Fuller Torrey.
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 Published and unpublished controlled studies that used serological methods for measuring T. gondii antibodies to assess inpatients and/or outpatients diagnosed with schizophrenia were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 Forty-two studies carried out in 17 countries over 5 decades were identified; 23 of these (6 unpublished) met selection criteria.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↗
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↗
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↗
Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains.
BACKGROUND: Previous studies of postmortem neurochemical markers in severe psychiatric disorders have been carried out on different brain collections, making it difficult to compare results. METHODS: One hundred RNA, protein, and other neurochemical markers were assessed in a single set of 60 postmortem brains (15 each with schizophrenia, bipolar disorder, major depression without psychosis, and unaffected control subjects) in relation to seven neurochemical systems. Quantitative measures of continuous variables for prefrontal, hippocampus, anterior cingulate, superior temporal cortex, or a combination of these were analyzed from published and unpublished studies by 56 research groups. RESULTS: Before correcting for multiple comparisons, 23% of markers (23/100) were abnormal in one or more regions, with most indicating decreased expression. The largest percentage were associated with the developmental/synaptic (10/22) and gamma-aminobutyric acid (GABA; 3/7) systems. Bipolar disorder (20) and schizophrenia (19) had the most abnormalities, with a 65% overlap. When all brain areas were considered together and corrected for multiple comparisons, reelin, parvalbumin, and GAD67 were the most abnormal. CONCLUSIONS: Confirming other studies, the GABA and developmental/synaptic neurochemical systems are promising areas for research on schizophrenia and bipolar disorder. Research should include tissue from both diseases, and additional brain areas should be assessed.
Adult↗
Does psychoanalysis have a future? No.
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Crime↗
Why some patients succeed.
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Adaptation, Psychological↗
Infectious pathogen detection arrays: viral detection in cell lines and postmortem brain tissue.
A unique array-based pathogen chip has been developed for the detection of viral RNA or DNA relevant to pathologies of the central nervous system. A total of 715 unique oligonucleotides (60-mer) representing approximately 100 pathogens were designed based on open reading frames (ORFs) from highly conserved and heterogenic regions within viral families. In addition, viral genes reflecting different stages of pathogen infection were also included to potentially define the stage of the viral infection. Viruses (double-stranded DNA, double- or single-stranded RNA, delta, retroid), parasites, and bacteria were included. Test samples labeled with Cy5 were examined by cohybridization with a reference RNA, labeled with Cy3, to the pathogen microarray chip. Good reproducibility of experiments was observed, based on data generated from duplicate hybridizations and duplicate spots on the microarray platform. A viral transcript detection sensitivity of 1 x 10(3) plaque-forming units (pfus) was achieved using selected cell lines and viruses. These findings suggest that the array-based platform described here is capable of detecting a broad spectrum of viruses in a single assay with relatively high sensitivity, specificity, and reproducibility. This method may be used to provide evidence of viral infection in postmortem tissue from psychiatric patients as well as a wide range of other diagnostic categories.
Autopsy↗
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↗
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↗
Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium.
Between 1997 and 2002, 48 data sets from the hippocampus were produced on samples from the Stanley Neuropathology Consortium. From these data sets, 224 total measures were available from the various subdivisions of the hippocampus. An integrative analysis of these measures was performed using a multivariate, nonparametric analysis of variance (ANOVA). ANOVA with correction for multiple comparisons indicated that parvalbumin-containing cells in CA2 were reduced in schizophrenia and bipolar disorder. In addition, reelin protein in the molecular layer of the dentate gyrus was decreased in schizophrenia, bipolar disorder, and depression at the trend level of statistical significance (P=0.065). These results strongly suggest a dysfunction of inhibitory GABA-ergic interneurons in severe mental illness. Without correction for multiple comparisons, 31 measures were abnormal in at least one disease, whereas 11 measures would be expected to appear abnormal by chance. Abnormal molecules included measures of synaptic density or neuronal plasticity (reelin, SNAP-25, BDNF, Complexin I and II), as well as parvalbumin, tyrosine receptor kinase A, glucocorticoid receptors, glutamate NR1 receptor subunits, serotonin 5HT2(A) and 5HT1(B) receptors, and dopamine D(5) receptors.
Analysis of Variance↗
PORT updated treatment recommendations.
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Acute Disease↗
Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii.
The exact mechanisms of action of some antipsychotics and mood stabilizers have not been elucidated. Response to these medications can vary among individuals. Recent studies indicate that infection with the parasite Toxoplasma gondii may contribute to the symptoms of schizophrenia in some individuals. We investigated commonly used antipsychotic and mood stabilizing medications for their ability to inhibit the replication of this organism. We employed a system for testing compounds for in vitro activity against T. gondii. Human fibroblasts (HFF) were treated with test compounds and then exposed to Toxoplasma that has been genetically modified to express cytoplasmic beta-galactosidase. Inhibition by the drugs was determined by spectrophotometric analysis of colorimetric reactions. We tested 12 neuroleptic compounds and found that of these, the antipsychotic haloperidol and the mood stabilizer valproic acid most effectively inhibit Toxoplasma growth in vitro. Valproic acid inhibited the parasite at a concentration below that found in the cerebrospinal fluid and blood of individuals being treated with this medication and displayed synergistic activity with haloperidol and with trimethoprim, an antibiotic commonly used to treat Toxoplasma infections.Several medications used to treat schizophrenia and bipolar disorder have the ability to inhibit the in vitro replication of T. gondii.
Animals↗
Herpesviruses and Toxoplasma gondii in orbital frontal cortex of psychiatric patients.
Herpes simplex virus (HSV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6) are viruses capable of establishing latency. All of these infect the CNS and have been detected in human postmortem brains. Toxoplasma gondii is a protozoan organism which can reactivate in the brains of previously infected immunocompromised individuals. To screen for the presence of herpesviruses and T. gondii in postmortem orbital frontal brain samples from patients with schizophrenia, affective disorders, and controls, we used nested-polymerase chain reaction (n-PCR)/sequencing. We identified HHV-6B sequences in 2/51 postmortem brain samples but no sequences from other herpesviruses. We did not detect sequences of T. gondii in the postmortem brains. Additional studies including ones directed at the sensitive detection of viral nucleic acids in multiple brain regions should be directed at confirming or excluding a role for viruses and protozoa in the etiology of these disorders.
Adolescent↗
A systematic review and meta-analysis of Northern Hemisphere season of birth studies in schizophrenia.
Based on the epidemiological finding that individuals with schizophrenia tend to be born in winter/spring when compared to the general population, we examined (1) the strength and timing of this effect in Northern Hemisphere sites, and (2) the correlation between the season of birth effect size and latitude. Studies were located via electronic data sources, published citations, and letters to authors. Inclusion criteria were that studies specify the diagnostic criteria used, that studies specify the counts of schizophrenia and general population births for each month, and that subjects and the general population be drawn from the same birth years and catchment area. We extracted data from eight studies based on 126,196 patients with schizophrenia and 86,605,807 general population births and drawn from 27 Northern Hemisphere sites. Comparing winter/spring versus summer/autumn births, we found a significant excess for winter/spring births (pooled odds ratio = 1.07; 95% confidence interval 1.05, 1.08; population attributable risk = 3.3%). There was a small but significant positive correlation between the odds ratios for the season of birth comparison and latitude (r = 0.271,p < 0.005). Furthermore, the shape of the seasonality in schizophrenia births varied by latitude band. These variations may encourage researchers to generate candidate seasonally fluctuating exposures.
Birth Rate↗
Fatal olanzapine-induced ketoacidosis.
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Adult↗
Toxoplasma gondii and schizophrenia.
Recent epidemiologic studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infections with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection with T. gondii can produce psychotic symptoms similar to those displayed by persons with schizophrenia. Since 1953, a total of 19 studies of T. gondii antibodies in persons with schizophrenia and other severe psychiatric disorders and in controls have been reported; 18 reported a higher percentage of antibodies in the affected persons; in 11 studies the difference was statistically significant. Two other studies found that exposure to cats in childhood was a risk factor for the development of schizophrenia. Some medications used to treat schizophrenia inhibit the replication of T. gondii in cell culture. Establishing the role of T. gondii in the etiopathogenesis of schizophrenia might lead to new medications for its prevention and treatment.
Adult↗