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)

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

We investigated verbal and spatial working memory in participants with childhood-onset schizophrenia (N=13), attention-deficit/hyperactivity disorder (ADHD; N=31) and age-matched normal children (N=27). The ages of the participants ranged from 9 to 20 years, with an average age of approx. 14 in all groups. Diagnoses were based on structured interviews (Kiddie-Schedule for Affective Disorders and Schizophrenia) with the children and their parents and made using DSM-III-R criteria. Verbal working memory was assessed by the highest number of digits recalled in forward and backward order on the Digit Span subtest of the Wechsler Intelligence Scale. Results showed that normal children recalled more digits than schizophrenic and ADHD children, who did not differ. Spatial working memory was assessed with the Dot Test of Visuospatial Working Memory: The children were presented with a dot on a page for 5 s and asked to mark its location on a blank page immediately after presentation or 30 s later. A distracter task was used during the delay to prevent verbal rehearsal. The average distance between the target dot and the child's mark in the 30-s condition was shorter for normal than for schizophrenic and ADHD children, who did not differ. Thus, both schizophrenic and ADHD children showed deficits in verbal and spatial working memory. These results suggest that in both disorders, the capacity of the sensory buffers may be diminished, and/or the availability and allocation of resources to the central executive may be limited.
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PMID:Working memory in childhood-onset schizophrenia and attention-deficit/hyperactivity disorder. 975 96

The aim of the present study is to examine attentional costs (inhibition) in covert visual attention in a group of acutely ill adolescents with schizophrenia without long histories of neuroleptic treatment. Variations in reaction time were analyzed for possible age and sex differences. Adolescents with schizophrenia (n = 19) were compared to a group of ADHD subjects (n = 20) and a group of normally functioning adolescents (n = 30) on a measure of covert visual attention. The results support a hypothesis of abnormally rapid disengagement (reduced costs) in male adolescents with schizophrenia. Such an abnormality has also been found in adults with chronic schizophrenia. Whether this holds true for both sexes of adolescents with schizophrenia or is restricted to male subjects cannot be answered with certainty due to the small number of females with schizophrenia in our sample. Our findings indicate, however, that there are some general sex differences and some specific sex differences related to covert visual attention in adolescents with schizophrenia.
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PMID:Covert visual attention in patients with early-onset schizophrenia. 985 Sep 86

Neuronal nicotinic acetylcholine receptors (nAChRs) are a class of ion channels with significant potential as molecular targets for the design of drugs to treat a variety of CNS disorders. The discovery that neuronal nAChRs are further subdivided into multiple subtypes suggests that drugs which act selectively at specific nAChR subtypes might effectively treat Parkinson's disease (PD), Alzheimer's disease (AD), schizophrenia, ADHD, depression, anxiety or pain without the accompanying adverse side effects associated with non-selective agents such as nicotine (1) and epibatidine. Altinicline (SIB-1508Y) is a novel, small molecule designed to selectively activate neuronal nAChRs and is undergoing clinical evaluation for the treatment of PD. It was selected from a series of compounds primarily on the basis of results from functional assays, including (a) measurement of Ca2+ flux in stable cell lines expressing specific recombinant human neuronal nAChR subtypes; (b) determination of in vitro and in vivo neurotransmitter release; (c) in vivo models of PD. Biological data on both altinicline and the series of compounds from which it was selected are reported.
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PMID:Recombinant human receptors and functional assays in the discovery of altinicline (SIB-1508Y), a novel acetylcholine-gated ion channel (nAChR) agonist. 1081 48

Over the past 10 years, innovations in physics and computer science have promoted magnetic resonance imaging (MRI) as an essential tool for investigating the biological substrates of psychiatric disorders. Requiring no radiation exposure, MRI is now the preferred imaging technique for pediatric populations. However, the rapid technical advances in MRI pulse sequences, data processing, and analysis have made it increasingly complex for clinicians to compare and critically evaluate MRI research studies. This paper selectively reviews MRI research on five psychiatric conditions occurring in childhood or adolescence: ADHD, autism, childhood-onset schizophrenia, Tourette syndrome, and early-onset depression. The selection of papers reviewed was based on four criteria: the originality of the idea underlying the paper, the quality of the sample and methodologies used, the presence of controversial findings in the paper, and whether the paper was a clear illustration of specific methodological strengths or weaknesses. The two goals of this review paper are to update clinicians on morphometric brain imaging in child psychiatry and the methodological issues pertaining to image acquisition and analysis, and to promote critical reading of future MRI studies.
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PMID:MRI neuroimaging of childhood psychiatric disorders: a selective review. 1103 81

This is a review of pharmacotherapy in children and adolescents with mental retardation from the perspective of DSM and ICD disorders. The existing research is reviewed in young people with mental retardation but, when data are lacking, we examined the literature from adults with mental retardation and from typically-developing children. The literature is discussed for each of the following disorders: ADHD, anxiety disorders, bipolar disorder, conduct disorder, depression, enuresis, schizophrenia, self injury, and tics and movement disorders. With the possible exception of ADHD, there is a woeful lack of empirical data on most of these disorders in young people with mental retardation. Clinicians will often be forced to extrapolate from data on adults having mental retardation and from typically-developing children. The best policy is probably to treat such patients cautiously, while gathering data on the effects of such therapy in the hopes of beginning a data base.
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PMID:Pharmacotherapy of disorders in mental retardation. 1114 Jul 85

Clinical trials indicate that inositol may be effective in the treatment of patients with depression, panic disorder and obsessive compulsive disorder (OCD), but not in the treatment of patients with schizophrenia, Alzheimer's disease, ADHD or autism. This spectrum of clinical action parallels that of serotonin selective reuptake inhibitors (SSRIs), but inositol is a precursor in the phosphatidylinositol cycle, a second messenger system distal to the receptor for 5HT-2. To study its mechanism of therapeutic action there is a need to test inositol's activity in animal models of psychopathology. In rats, chronic inositol was demonstrated to increase activity levels, reduce immobility time in the forced swim test and in the reserpine-induced hypoactivity models of depression, and reduce anxiety-like behaviors in the elevated plus-maze. The reduction in anxiety-like behaviors appears to be related to baseline levels of activity. Inositol treatment was not observed to have any effect on amphetamine-induced hyperactivity, apomorphine-induced stereotypy, or on the performance of memory tasks by monkeys. Clinical controlled trials of inositol in patients with depression, panic disorder, and OCD were small, and positive psychoactive effects in animals clearly strengthen the case for further clinical trials and potential for general therapeutic use in humans.
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PMID:The effects of inositol treatment in animal models of psychiatric disorders. 1117 78

alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype.
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PMID:An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans. 1131 18

Velo-cardio-facial syndrome (VCFS) is a congenital malformation syndrome with variable phenotypic features that has been associated with chromosomal microdeletion 22q11.2. Psychiatric disorders have been reported to be highly prevalent in individuals with this syndrome, and the objective of this study was to assess the nature and extent of psychopathology among individuals with VCFS. We studied 20 children and adolescents with 22q11 deletions determined by fluorescence in situ hybridization (FISH). Control subjects were 11 nondeleted siblings who were the closest age match to the affected subjects. Both affected and control subjects were assessed using two standardized psychiatric research instruments. The results of this study confirmed the high rate of psychiatric disorders among VCFS subjects (60% of our subjects). Of the specific types of disorders, only mood disorders were significantly more common among VCFS subjects compared to sibling controls, with eight VCFS subjects having mood disorders compared with none of the control subjects (P<0.02). Three affected subjects had schizotypal traits comorbid with a mood disorder. In addition, disruptive behavior disorders were frequently diagnosed among VCFS subjects. Using a dimensional measure of psychopathology, significant differences between VCFS subjects and sibling controls were found on three scales: ADHD (P<0.02), separation anxiety (P<0.02), and depression (P<0.01). VCFS subjects were achieving significantly less well academically and requiring significantly more special educational assistance than sibling controls. Follow-up data were available on two subjects, both of whom had been diagnosed with schizophrenia. Further research on psychopathology in VCFS may provide a model of how a specific genetic defect can lead to the development of psychiatric disorders.
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PMID:Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders. 1137 50

Looking at the field as a whole through metaanalysis, Shadish et al concluded (based on 162 studies) that marital and family therapies were significantly more effective than no treatment and at least as effective as other forms of psychotherapy. Although these reviews and others are positive, individual studies raise many questions. For instance, based on research findings, family treatments increasingly have become standard care for patients with schizophrenia. It remains unclear what degree and type of family involvement is needed for which patients at which stage of their disorder. In the area of anxiety and depression, there are too few studies to make any strong conclusion. Although investigators such as Barrett, Cobham, and Diamond have produced some positive results, the Lewinsohn and Clark studies fail to demonstrate the added benefit of family involvement. Although Brent's study showed CBT to reduce depression faster, family therapy and supportive therapy did just as well in the long run, and family conflict was a strong risk factor for relapse. In the area of anorexia, Russell and Robins produced strong results from family interventions, whereas Geist found no difference between different types of family interventions. Family treatments for obesity have been inconsistent. In a metaanalysis of 41 studies, parental involvement did not contribute significantly to outcomes. In the Epstein study, however, which included 5- and 10-year follow-up, the results of family intervention were impressive. Although many of these studies can be cited for various methodologic flaws, the most consistent problem is that sample sizes are too small to detect difference between two or more active treatments. The most consistent findings (and most well-done, large studies) that support the efficacy of family-based interventions are done with externalizing problems. Work groups led by Patterson, Eisenstadt, Webster-Stratton, Alexander, and Henggeler all have produced impressive reductions of oppositional and antisocial behavior. Clinical programs that treat these populations without using a family-based intervention as at least a component of a treatment package are seriously ignoring the findings of contemporary intervention science. Programs of research by Henggeler, Szapocznik, and Liddle demonstrate similarly impressive results for substance abusing adolescents. Although preliminary results from the Dennis et al study suggest that various treatment approaches may benefit this population. Family interventions have had less success in reducing ADHD symptoms, yet these psychosocial treatments have been essential in reducing much of the family and school behavior problems associated with this disorder. Many investigators would agree that a combined medication and family treatment approach may be the treatment of choice for children with ADHD. In fact, many studies across various disorders suggest that patients respond best to comprehensive treatment packages, of which a family treatment is at least one component. Although the data are promising, many challenges lie ahead. Although collectively many family intervention studies exist, many disorders lack enough rigorous and large-scale investigations to make any strong conclusions. Kazdin argues that sample sizes of 150 are essential to detect significant differences between active treatments, and few of the reviewed studies include these kinds of patient numbers. Furthermore, not enough committed and sophisticated family treatment researchers have carried out some of the major studies. For example, the Brent study on depression and the Barkley study of ADHD, although testing family approaches, lacked well-developed and published treatment manuals, a demonstration of the necessary expertise to supervise these treatments, and data about training and adherence to these models. Although the absence of expertise limits investigator allegiance biases, treatment development and modification are essential for tailoring family treatments to target family processes specific to each disorder. Investigators such as Patterson and Liddle have invested great effort in rigorously dismantling the treatment process, identifying and refining essential ingredients, and repackaging more potent treatment protocols. This process has paid off well. Programmatic treatment development is needed for many disorders to address myriad questions. What are the essential disorder-specific family processes that should be targeted by interventions? Hostility, criticism, communication, attachment and autonomy, attributional sets, and behavior management are important processes of family life, but each may have more relative importance for specific disorders. With a greater understanding of these processes, treatments could be tailored to target these mechanisms more efficiently and effectively. (ABSTRACT TRUNCATED)
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PMID:Current status of family intervention science. 1144 17


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