Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Levels of biopterin derivatives in urine, serum, milk, cerebrospinal fluid, brain, and liver have been measured with the Crithidia fasciculata assay. Normal levels in serum and urine have been given and compared with those in a number of benign and malignant proliferative disorders, phenylketonuria, kidney disease, Parkinson's disease, schizophrenia, controlled epilepsy, rheumatoid arthritis, and pernicious anaemia. The active component of Crithidia factor in serum was 7,8-dihydrobiopterin. Tissue, urine, and some serum samples contained two active materials, the principal one being 7,8-dihydrobiopterin; a minor constituent was probably tetrahydrobiopterin. Serum biopterin levels following methotrexate administration were raised and subsequent administration of folic acid and 5-formyltetrahydrofolic acid further increased serum levels of biopterin derivatives; this was in contrast to the total absence of response to oral folates without prior methotrexate and to 5-methyltetrahydrofolic acid either with or without methotrexate being given.
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PMID:Biopterin derivatives in human body fluids and tissues. 93 31

In the clinical picture of 121 patients from 1 to 14 years among the group of 250 with phenylketonuria (48.4%), besides symptoms of mild mental retardation, there were also signs of autism, shallow emotional reactions and catatonic disturbances. This group was distinguished as a special schizophreno-like variant of phenylketonuria. A study of the age and therapeutical dynamics of the psychotic symptomatology has demonstrated that the schizophreno-like syndrome in phenylketonuria may be transient (63 cases) and more stable (58 cases) and does not depend upon the content of hyperphenilalaninemia, the genetical variant of the disorder and hereditary loading by schizophrenia. It is concluded that the schizophreno-like symptomatology in phenylketonuria develops due to a pleiotropic effect of the phenylketonuric gene.
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PMID:[A schizophrenia-like variant of phenylketonuria]. 121 Sep 31

A professor proposes a populationwide system to reduce the prevalence of mental disorders among children in the Americas. He bases his proposal on experience in the US, but the US is a heterogeneous society with some people living in poverty similar to conditions in developing countries and others having a relatively high living standard. Even though the emphasis on each component varies from country to country, any national plan should consist of the following components: family planning; prenatal care; immunization; optical nutrition; child safety; home visiting and day care; school based, health and family life education programs; and development of mental health awareness and skills in primary care facilities. Countries with highly developed health services should also include newborn screening of congenital metabolic abnormalities such as the correctable conditions of phenylketonuria, galactosemia, and congenital disorders of thyroid function. These screening programs should not exist without an extensive follow up program. Primary health care workers in clinical settings can also contribute to the prevention of mental disorders among children by prescribing to appropriate clinical practices. They must undergo training to recognize and manage these disorders. Health workers and school teachers must be trained to identify child neglect and abuse and to refer cases to the appropriate community agencies. Foster care should be only a temporary solution. If the neglect and abuse are chronic, the child should be become available for adoption. Improved obstetric care, better effective accident prevention, and timely treatment of central nervous system infections are needed to prevent epilepsy. Certain drugs are secondary prevention techniques to control schizophrenia and affective disorders.
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PMID:Child mental health in the Americas: a public health approach. 138 73

There are reports in the literature that suggest slightly impaired average intellectual ability, slightly increased signs of brain irritability, and possibly, a slightly increased susceptibility to late-onset schizophrenia with depressive signs, reproductive anomalies, and varicose veins in heterozygotes for phenylketonuria (PKU). The possible significance of such results for our understanding of genetic liabilities for common disease, or of genetic variability influencing mental performance in the normal range is discussed.
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PMID:Phenotypic deviations in heterozygotes of phenylketonuria (PKU). 401 7

We have developed a two-tiered approach to elucidating the genetic predisposition to schizophrenia. The approach first involves the examination of candidate genes in a subset of schizophrenic individuals to identify DNA sequence variations of likely functional significance, i.e., that produce either structural alterations in the protein or affect the level of gene expression. Once identified, the prevalence of the aberrant allele is examined in a large group of unrelated schizophrenic cases and controls to assess whether a true disease association exists. Herein, we describe the establishment of a DNA bank on nearly 200 unrelated schizophrenic cases defined by DSM-III-R criteria and on over 300 unrelated, ethnically similar controls. Characteristics of the study sample are described. The study approach then is illustrated by testing known mutations in the phenylalanine hydroxylase gene, responsible for the autosomal recessive disease of phenylketonuria, in the case-control sample to determine if carriership of a mutant allele is associated with an increased risk of schizophrenia. Using PCR amplification of specific alleles (PASA), we screened 190 schizophrenic cases and 336 controls for two common point mutations in the phenylalanine hydroxylase gene. Two carriers were found among the controls, while none of the cases was shown to carry a mutant allele. Thus, carriership of either of two common mutations in the phenylalanine hydroxylase gene does not appear to be associated with an increased risk of schizophrenia. As additional candidate genes are tested in this case-control resource, adjustment for multiple comparisons will become crucial in order to reduce the chance of false positive findings.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Novel association approach for determining the genetic predisposition to schizophrenia: case-control resource and testing of a candidate gene. 807 67

Single-photon emission computed tomography (SPECT) of the brain has been used to define functional abnormalities in two groups of childhood behavior disorders: (1) a "primary" category in which there is exclusive or predominant presentation with cognitive and/or behavioral dysfunction and (2) encephalopathies, often defined etiologically at the biochemical or molecular level, in which clinical expression includes, but is not confined to, neural dysfunction. Radiopharmaceuticals available for such studies are manifold, but those used to date have been predominantly perfusion agents, eg, Xenon-133 (133Xe) and technetium-99m (99mTc) hexamethylpropylene amine oxime, and studies with [99mTc]bicisate are eagerly awaited. Xenon-133 studies require that the patient be in the field of view of the detector while the tracer is administered. This renders it difficult for a subject to perform cognitive and other exercises while being imaged, because the environment is quite foreign. On the other hand, the 99mTc-labeled perfusion agents permit a scintigraphic "snapshot" of regional cerebral blood flow during a behavioral event without having to have the patient under the imaging instrument. Thus, one can separate the administration of the radiotracer, which can be done under more controlled and physiological conditions, from the actual imaging. In addition, greater spatial resolution is achieved with the technetium-based agents. Currently, multidetector or dedicated annular crystal-type cameras are the preferred brain SPECT devices, and they are essential to applications such as cortical "activation mapping" or tomographic detection of receptor systems. Close attention to technical detail and standardization of the child's behavioral environment during the investigation are critical to a successful study. The relative advantages and disadvantages of qualitative versus semiquantitative analysis of imaging date are reviewed. Among primary behavioral disorders, 133Xe SPECT studies in attention deficit disorder-hyperactivity (ADHD) have suggested a pattern of hypoperfusion of striatal and periventricular structures with sensorimotor cortical hyperperfusion. This pattern is consistent with some neurophysiological models of the disorder. In cerebral palsy, perfusional abnormalities have paralleled clinical deficits and may offer information to help predict outcome. The important field of childhood affective disorders (schizophrenia, juvenile autism, depression, etc) remains largely unstudied with SPECT. Finally, representative examples of the use of SPECT to study perfusion in encephalopathies with behavioral expression (phenylketonuria, MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) syndrome, Wilson's disease, etc) are given.
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PMID:Brain single-photon emission computed tomography for behavior disorders in children. 837 98

The dopamine (DA) neurons projecting to the prefrontal cortex (PFC) are thought to be involved in working memory, stress response, and the pathogenesis of schizophrenia. In this commentary, we review the current evidence supporting a precursor tyrosine dependence of these mesoprefrondal DN neurons. Several studies in rats employing different experimental paradigms [i.e. experimental diabetes and early-treated phenylketonuria (PKU) model] have shown that reduced tyrosine levels in brain can affect markedly the physiology and functions of these DA neurons. However, supplemental tyrosine is effective in enhancing functional transmitter outflow from mesoprefrontal DA neurons only under conditions where their physiological activity is enhanced and DA synthesis and release are uncoupled from intrinsic regulatory controls. Recent studies in humans have also suggested that variations in brain tyrosine levels can affect significantly higher cortical functions subserved by the PFC. In early-treated PKU patients with mildly reduced tyrosine levels, marked impairments in cognitive functions dependent on the dorsolateral PFC could be detected. In drug-treated schizophrenic patients, supplemental tyrosine was shown to have a disruptive effects on the smooth-pursuit eye movement performance task. Furthermore, tyrosine administration was effective in restoring impaired working memory in humans following cold stress paradigm, as assessed by a computer-based delayed matching to-sample memory task. These human studies, together with the current evidence obtained from animal experiments, suggest that the functions of the mesoprefrontal DA neurons can, under certain circumstances, be readily influenced by the availability of the precursor tyrosine.
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PMID:Mesoprefrontal dopaminergic neurons: can tyrosine availability influence their functions? 910 94

A case report of a 16-year-old boy with the classical form of phenylketonuria (PKU) and suffering from a delusional disorder is presented. He did not respond to a traditional antipsychotic medication but improved on an atypical antipsychotic, risperidone. The cerebrospinal fluid metabolites of the biogenic amines were measured and are also reported in the context of a recent interest in the ratios of these amine metabolites in schizophrenia. It is proposed that such dually diagnosed patients with PKU may provide a model in which to test the prevalent biogenic amine theories in psychiatric disorders.
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PMID:Delusional disorder in a boy with phenylketonuria and amine metabolites in the cerebrospinal fluid after treatment with neuroleptics. 950 13

Whereas a growing interest in the development of attentional flexibility (AF) and in perseverative behavior, being one marker of this component, exists in neuropsychological studies and in the domain of developmental psychopathology (e.g., PKU, infantile schizophrenia, autism and Parkinson's disease) (Pennington & Ozonoff, 1996; Stahl & Pry, 2002), only a few studies have concerned themselves with this subject in normal children. It is thus of interest to add more empirical data to the existing literature in this domain. Therefore, the aim of our study was to explore the development of AF and of perseverative errors in young preschool children with normal development, aged 1.5 to 6 years. Using set-shifting tasks of increasing difficulty level, three age groups were compared with respect to their AF skills. Results show a developmental factor underlying AF, with different levels of this form becoming more and more complex with age, ranging from a rudimentary visual form to a complex representational form of flexibility. Overall, few perseverative errors occurred and they decreased with age. Results are discussed from a developmental and neuropsychological perspective.
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PMID:Attentional flexibility and perseveration: developmental aspects in young children. 1603 43

Recessive mutations in the phenylalanine hydroxylase (PAH) gene predispose to phenylketonuria (PKU) in conjunction with dietary exposure to phenylalanine. Previous studies have suggested PAH variations could confer risk for schizophrenia, but comprehensive follow-up has not been reported. We analyzed 15 common PAH "tag" SNPs and three exonic variations that are rare in Caucasians but common in African-Americans among four independent samples (total n = 5,414). The samples included two US Caucasian cohorts (260 trios, 230 independent cases, 474 controls), Bulgarian families (659 trios), and an African-American sample (464 families, 401 controls). Analyses of both US Caucasian samples revealed associations with five SNPs; most notably the common allele (G) of rs1522305 from case-control analyses (z = 2.99, P = 0.006). This SNP was independently replicated in the Bulgarian cohort (z = 2.39, P = 0.015). A non-significant trend was also observed among African-American families (z = 1.39, P = 0.165), and combined analyses of all four samples were significant (rs1522305: chi(2) = 23.28, 8 d.f., P = 0.003). Results for rs1522305 met our a priori criteria for statistical significance, namely an association that was robust to multiple testing correction in one sample, a replicated risk allele in multiple samples, and combined analyses that were nominally significant. Case-control results in African-Americans detected an association with L321L (P = 0.047, OR = 1.46). Our analyses suggest several associations at PAH, with consistent evidence for rs1522305. Further analyses, including additional variations and environmental influences such as phenylalanine exposure are warranted.
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PMID:Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples. 1893 93


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