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

Association studies with the DRD2 Taq1A marker have been variable in implicating DRD2 as a "Reward Deficiency Syndrome Gene" for alcoholism and substance abuse. Given that the Taq1A marker is not functionally significant, second-generation studies on the DRD2 receptor to identify functional variants and evaluate their effect on the phenotype are the logical step towards confirming and extending the DRD2 hypothesis. This article discusses the implications and process of progress made in these directions. The new findings are the description of structural variants in the D2 receptor, the demonstration that one of these, Ser311Cys, largely prevents signal transduction following receptor activation and the use of Ser311Cys in a large association and sib-pair linkage anlysis in an American Indian isolate. In this particular population, the Cys311 variant is far more abundant (0.16) than in Caucasians (0.03). Genotyping of Ser311Cys, the DRD2 intron 2 STR, and the Taq1A marker in 459 subjects, including 373 sib-pairs and 15 Cys311/Cys311 homozygous individuals, revealed no association to alcoholism, substance use disorders, or schizophrenia. The implication is that a DRD2 variant that dramatically impairs receptor function was not sufficient to significantly alter alcoholism vulnerability in a relatively large and also genetically and environmentally homogeneous sample.
 ...
PMID:A functionally deficient DRD2 variant [Ser311Cys] is not linked to alcoholism and substance abuse. 965 Jun 35

The Proxy for the Deficit Syndrome (PDS) was used with longitudinal symptom assessment data to identify recent-onset schizophrenia patients with the deficit syndrome. We evaluated the stability of deficit symptoms using repeated assessments. Symptom ratings were examined at an initial point of outpatient stabilization on antipsychotic medication as well as prospectively over the subsequent 12 months of outpatient treatment and assessment in 83 recent-onset schizophrenia patients. The vast majority of patients who were classified as non-deficit at the cross-sectional baseline assessment continued to remain non-deficit throughout the first year of treatment. However, patients classified as deficit at baseline did not consistently remain classified as showing deficit syndrome during the follow-through period. Thus, the presence of deficit symptoms detected in a single cross-sectional rating may be an inaccurate way to rate the deficit syndrome, yielding excessive false positives. Our use of longitudinal data allowed the stability criterion of the deficit syndrome to be evaluated using the PDS.
 ...
PMID:Prediction of the deficit syndrome from initial deficit symptoms in the early course of schizophrenia. 972 63

Previous studies have shown that anhedonia characterizes the deficit syndrome of schizophrenia. Anhedonia is also one of the main symptoms of the depressive state. The purpose of this study was to examine the relationships between anhedonia and depression in the deficit syndrome of schizophrenia. Self-evaluations of anhedonia and depression were performed by three groups of subjects (32 deficit schizophrenics, 32 major depressives, 35 healthy subjects) matched for sociodemographic variables. Deficit schizophrenics and major depressives are more anhedonic than controls, but there is no difference between the two study groups. Contrarily to what is evidenced for major depressives and for healthy subjects, the depressive symptomatology correlates with anhedonia in deficit schizophrenics. When deficit schizophrenics are dichotomized into depressed versus non-depressed patients, no difference is observed concerning anhedonia. These results suggest that anhedonia in the deficit syndrome of schizophrenia has no specificity but appears independent of coexisting depression and covaries with several characteristics of depression (retardation, cognitive distortions). Our results support the hypothesis that the deficit syndrome of schizophrenia could constitute a non-depressive mood disorder.
 ...
PMID:Anhedonia in the deficit syndrome of schizophrenia. 1036 31

Three problems in identifying genes causing schizophrenia and other developmental disorders may be locus heterogeneity, high disease allele frequency, and unknown mode of inheritance. The DNA polymorphism-diet-cofactor-development (DDCD) hypothesis addresses the first two. The gene-teratogen model addresses the third. The DDCD hypothesis is that schizophrenia results in part from brain abnormality in utero from the aggregate effect of multiple mutations of small effect of genes related to important cofactors (e.g., folate, cobalamin, or pyridoxine) potentiated by maternal dietary deficiency of these cofactors and by pregnancy. The effect results from insufficiency of the cofactors and from resulting effects such as impaired DNA synthesis, immune deficiency, effects on niacin and serotonin metabolism, and teratogens, e.g., hyperhomocysteinemia. The hypothesis addresses all of the unusual features of schizophrenia: e.g., decreased brain gray matter, birth-month effect, geographical differences, socioeconomic predilection, association with obstetrical abnormalities, decreased incidence of rheumatoid arthritis, and association with famine and viral epidemics. In the gene-teratogen model, a teratogenic effect in utero produces a developmental disorder through a teratogenic locus and a modifying or specificity locus, as well as through environmental factors. An example is the major intrauterine effect seen in offspring of phenylketonuric mothers. Thus, the mode of inheritance of genes acting prenatally may in some cases be fundamentally different from that of genes acting postnatally. The model is interesting because it is simple and because teratogenic loci will be difficult to locate by conventional linkage mapping techniques due to misspecification of the affection status of both mother and affected children. A new study design is suggested for identifying teratogenic loci.
 ...
PMID:DNA polymorphism-diet-cofactor-development hypothesis and the gene-teratogen model for schizophrenia and other developmental disorders. 1040 96

Although emotional dysfunction is presumed to be a central part of the deficit syndrome in schizophrenia, it has not yet been empirically investigated in deficit and non-deficit patients. Emotional responding was examined in 19 male deficit patients, 22 non-deficit patients, and 20 non-patient controls. Patients participated in a semi-structured clinical interview that included questions from the Schedule for the Deficit Syndrome (SDS) and the Brief Psychiatric Rating Scale (BPRS), and then were then categorized into deficit and non-deficit groups. In addition, all participants viewed emotional films while their facial expressions were videotaped and then completed self-reports of emotional experience following each film. As predicted, deficit patients were less expressive than non-deficit patients and controls across the films. Contrary to prediction, deficit patients did not report experiencing less emotion to the films than non-deficit patients or controls. Thus, a disjunction in emotional responding appeared to characterize deficit patients, who were less expressive than controls but did not report less emotional experience. Alternative explanations for the findings are considered as are directions for future research.
 ...
PMID:Emotional responding in deficit and non-deficit schizophrenia. 1062 40

The historical and genetic foundations of our current understanding of schizophrenia are reviewed, as are the present and future directions for research. Genetic epidemiological investigations, including family, twin, and adoption studies have confirmed the contributions of genetic and environmental determinants of schizophrenia. For example, identical twins show average concordance rates of only 50%; rates of 100% would be expected on the basis of genetic equivalence alone. Genetic factors may cause errors in brain development and synaptic connections. A broad range of environmental components may further damage the brain. Biological components may include pregnancy and delivery complications, such as intrauterine fetal hypoxia, infections, and malnutrition. Primarily nonbiological components may include psychosocial stressors, such as residence in an urban area and dysfunctional family communication. It is likely that the environmental factors interact with the genetic liability in a negative manner to produce disorders in the schizophrenic spectrum. Genetic and environmental components of the disorder are examined, as well as their interactions in producing either neurodevelopmental syndromes or schizophrenia itself. The implication of these findings for prevention and treatment are considered.
 ...
PMID:Schizophrenia: genes and environment. 1068 18

Seventy-four patients with a recent initial onset of schizophrenia were studied during an inpatient hospitalization for a recent onset of schizophrenia as well as during a 12-month period of outpatient treatment as part of a large longitudinal study at UCLA. The Proxy for the Deficit Syndrome (PDS; Kirkpatrick, B., Buchanan, R.W., Carpenter, W.T., 1993. Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Research 47, 47-56.) was calculated based on psychiatric symptoms rated on the Brief Psychiatric Rating Scale every 2 weeks throughout the 12 months. The Minnesota Multiphasic Personality Inventory (MMPI) was administered to the schizophrenia patients at the index hospitalization. The 168-item version of the MMPI (MMPI-168) was administered at the baseline point of the 12-month period of outpatient treatment, and again 1 year later. Normal comparison subjects were tested with the MMPI or MMPI-168 at comparable time intervals. The UCLA Social Attainment Scale, a measure of the adequacy of social functioning and relatedness, was examined at the outpatient baseline and 12-month points. During the outpatient period, the Deficit Schizophrenia group (i.e. schizophrenia patients with high 12-month average PDS scores) had lower T-scores than the Non-deficit Schizophrenia group on several MMPI-168 scales, especially scales related to affective distress and anxiety. The MMPI-168 scores of normal subjects were generally the lowest of the three groups, but not always significantly lower than those of the Deficit Schizophrenia group. Social functioning at the end of the 12-month period was worst for the patient group with high deficit (PDS) scores. The findings are congruent with the concept of a Deficit Syndrome for which the PDS is the proxy.
 ...
PMID:MMPI discriminators of deficit vs. non-deficit recent-onset schizophrenia patients. 1072 28

A number of studies have shown that patients with schizophrenia smoke more than other psychiatric patients and more than the general population. Also, medicated schizophrenics who smoke present more positive symptoms of schizophrenia than non-smokers. The objective of the present study was to assess the effect of smoking on ratings of psychopathology for 30 days following discontinuation of antipsychotic medication. The subjects were 101 treatment-resistant patients with schizophrenia who had been admitted to the inpatient service of Neuroscience Research Hospital (NRH), National Institute of Mental Health, between 1982 and 1994 to undergo studies involving discontinuation of antipsychotic medication. Patients were rated independently on a daily basis on the 22-item Psychiatric Symptom Assessment Scale (PSAS), an extended version of the Brief Psychiatric Rating Scale (BPRS). At baseline, ratings for Verbal Positive, Paranoia and Loss of Function were higher in smokers (n=65) than non-smokers (n=36), but a statistically significant difference was observed only for the Verbal Positive cluster. Analysis by gender revealed that male non-smokers had the lowest psychopathology ratings at baseline. There were no differences in Anxiety/depression, Behavior Positive, Deficit Symptoms or Mannerisms (a measure for abnormal involuntary movements). Following medication discontinuation, repeated-measure analysis demonstrated a 'time' effect for all the variables studied and a 'group' (smokers vs. non-smokers) effect for Verbal Positive, Paranoia, and Loss of Function. Post-hoc comparisons at individual time points showed significantly higher ratings for smokers at week 1 for Paranoia. No differences were observed at later time points. In conclusion, at baseline, smokers had more positive symptoms and were apparently more functionally impaired than non-smokers. This difference was no longer evident after a 30 day medication discontinuation period.
 ...
PMID:Effects of smoking during antipsychotic withdrawal in patients with chronic schizophrenia. 1112 Apr 24

Genetic, epidemiologic, and molecular studies concur that liability to schizophrenia is transmitted through the inheritance of a number of genes of relatively small effect, some of which are shared with other psychoses. Each of these susceptibility genes causes minor deviations that are relatively innocent in themselves, for example, increased lateral ventricular volume, schizotypal personality, or subtle cognitive difficulties. However, when an individual is unlucky enough to inherit several of these traits, their cumulative effect, often compounded by environmental hazards, propels that person over a threshold for the expression of frank psychosis. Early environmental risk factors for schizophrenia include urban and winter birth, fetal malnutrition and hypoxia, and possibly prenatal viral infections; these early hazards have only a modest risk-increasing effect, and operate in the context of genetic risk. Preschizophrenic children are more likely to have minor psychomotor and cognitive problems; low IQ has a linear relationship with risk for schizophrenia. However, schizophrenia is not simply a neurodevelopmental disorder, because risk factors have been identified that have their effects proximal to the onset of psychosis: drug abuse, immigrant status, and social adversity and isolation. Both genetic and environmental risk factors appear to operate across diagnostic categories and therefore support a dimensional model of psychosis.
 ...
PMID:What risk factors tell us about the causes of schizophrenia and related psychoses. 1112 84

54 patients, 24 men and 30 women, (mean age 27 years) were examined. Two types of obsessive-phobic disorders with the phenomena of mysophobia were distinguished: obsession of the external (extracorporal) threat and obsession of contamination. Disorders of the first type (25 cases) were observed in psychopathic-like schizophrenia. They were characterized by a fear of possible contacts with different pathogenic agents--toxic substances, sharp small subjects, bacteria. Obsessions presented with a system of actions preventing phobic situations (rituals). With progression of the disease there was a decrease of both the degree and affective saturation of phobic disorders together with preserving rituals. Negative disorders presented with rough psychopathic-like changes with features of the "verschroben" defect. The disorders of the second type (29 patients) were observed in neurosis-like schizophrenia. Mysophobia manifested with both the repeated control and the fear of contamination accomplished. Ritual behavior presented with repeated actions and repeated control of the "sterility" of the own body and the surrounding subjects. Dynamics of these disorders was characterized by a tendency to more severe rituals of the control and persisting anxiety. Deficit disorders manifested with mental infantilism with psychopathic-like disorders of schizo-anancastic sphere. The above types of the obsessive-phobic disorders have a differential-diagnostic significance in respect of clinical variations of schizophrenia and determination of the state acuity with possible reversibility of the disorders (in neurosis-like schizophrenia).
 ...
PMID:[Obsessive-phobic disorders with the phenomena of mysophobia in slowly progressing schizophrenia]. 1124 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>