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)

The idea of lithium's specificity for bipolar disorder was proposed in Cade's original work in 1949. Since then, many controlled studies have been performed, examining lithium for treatment of bipolar disorder and other psychiatric conditions. This review was undertaken to determine if the suggestion of lithium's specificity has support in the controlled studies conducted after Cade's initial proposal. Studies were selected in a Medline search, dating back to 1966 and also identified from the bibliography of some of these papers. The controlled trials with lithium for the treatment of mania and bipolar depression, unipolar depression, schizophrenia, and schizoaffective disorder were reviewed. The published studies with lithium in other neuropsychiatric conditions were also considered. Additionally, we reviewed literature on other therapeutic agents proposed for bipolar disorder, looking at their comparative effectiveness to lithium. The data analyzed give strong support for lithium's being most effective in bipolar disorder, with minimal or no therapeutic effects in other neuropsychiatric disorders. The neurochemical underpinnings of this specificity are being investigated, without conclusive findings to date. The study of this paradigm of specificity in neuropsychopharmacology research may lead to meaningful contributions to understanding the pathophysiology of bipolar disorder and may help to develop newer treatments for this condition.
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PMID:The lithium ion: a foundation for psychopharmacological specificity. 965 4

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.
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PMID:A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder. 970 39

A common missense mutation of the methylenetetrahydrofolate reductase (MTHFR) gene (C677T) has been shown to be a risk factor for premature cardiovascular disease and neural tube defect. Deficient activity of MTHFR has also been implicated in the pathogenesis of psychiatric conditions such as schizophrenia and affective disorders. Arinami et al found an increased frequency of homozygosity for the mutated type (T677) of the MTHFR gene in schizophrenia and depression. We tried to replicate this finding in a sample of 343 patients with schizophrenia, 143 with bipolar disorder, 71 with unipolar depression, and 258 controls; however, there was no significantly increased frequency of homozygosity for the T677 allele in any of the diagnostic groups, compared to the controls. Our results suggest that homozygosity for the T677 allele of the MTHFR gene is unlikely to play a major role in the pathogenesis of schizophrenia or affective disorders in our sample.
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PMID:C677T polymorphism in methylenetetrahydrofolate reductase gene and psychoses. 1020 43

A retrospective survey on drug prescription over a one-year period (1989) in 1083 patients (48.3% of whom were male) hospitalized in a psychiatric university hospital in Switzerland and a 35-day prospective study (1992) on the prescription of "as needed" (prn) medication in a closed and an open ward were carried out. Their aim was to establish a basis for a monitoring of prescription habits and for pharmacoeconomic considerations. In the retrospective study, 48.3% of the patients were male. The mean duration of hospitalization of the patients was 47.0 +/- 68.1 days (mean +/- s.d.). Only 11 out of the 1083 patients (1%) were without psychotropic medication. The mean (+/- SD) number of drugs/day the patients were prescribed was 4.6 +/- 2.8, including 3.2 +/- 1.7 psychotropic drugs. Patients suffering from schizophrenia (67 d) or from unipolar depression (67.4 d) were hospitalized for the longest periods. Antipsychotics (67.5% of the patients) were the most frequently prescribed psychotropic drugs, followed by anxiolytics (42.2%), antidepressants (28.3%), hypnotics (31.4%) and mood stabilizers (7.1%). Antiparkinsonian agents accounted for 4.6% of all prescriptions. Levomepromazine, haloperidol (30.9% of all patients) and clotiapine were the most often prescribed neuroleptics, and clozapine was administered to only 6.4% of all patients. Among the antidepressants, maprotiline (11.9% of all patients) was more frequently prescribed than the classical tricyclic antidepressant amitriptyline, while the only available SSRI fluvoxamine and MAO inhibitors were rarely used. The most frequently prescribed anxiolytics were clorazepate (28.2% of all patients), lorazepam, bromazepam, and prazepam. Among the hypnotic drugs, chloral hydrate (11.5%) was more frequently administered than the first-ranking benzodiazepine flunitrazepam (7.8%). In the prospective study, 97% and 77% of the patients (n = 55) of the closed (n = 29) and of the open ward, respectively, were prescribed "as needed" (prn) drugs. However, only 71 and 80%, respectively, of these patients finally received the drug. The frequency of prescription was 34.9% for neuroleptics, 15.1% for anxiolytic drugs, 8.2% for non-benzodiazepine hypnotics and only 2.1% for benzodiazepine hypnotics. The most frequently prescribed neuroleptic drug was clotiapine (18% of all patients), but finally, only 29% of the prescribed doses were administered. Studies of this type are biased by the fact that local habits of prescription do not allow generalisation of the findings. Such surveys should be carried out more frequently and simultaneously in different centers. Critical comparisons could help to optimize treatment.
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PMID:Psychotropic drug prescription in a psychiatric university hospital. 1007 Nov 80

Our findings in the Helsinki Influenza Study and the Danish Forty Year Study lead us to conclude that a 2nd-trimester maternal influenza infection may increase risk for adult schizophrenia or adult major affective disorder. More recently we have also reported an increase of unipolar depression among offspring who were exposed prenatally to a severe earthquake (7.8 on the Richter scale) in Tangshan, China. Among the earthquake-exposed males (but not the females), we observed a significantly greater depression response for those individuals exposed during the 2nd trimester of gestation. These findings suggest that maternal influenza infection and severe maternal stress may operate (in different ways) as teratogens, disrupting the development of the fetal brain and increasing risk for developing schizophrenia or depression in adulthood.
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PMID:Prenatal teratogens and the development of adult mental illness. 1053 19

There have been repeated reports that Afro-Caribbean people living in the UK are more prone than white people to be diagnosed as having schizophrenia and mania, along with some evidence that they are less likely to receive a diagnosis of depression. We attempted to replicate these findings in a population of patients on lithium prophylaxis. We therefore assessed the clinical characteristics of people under the age of 55 from three ethnic groups attending a lithium clinic in south London, those of (1) white British (n = 88); (2) Afro-Caribbean (n = 31); and, (3) African (n = 15) origin. Nineteen of the white patients met DSM-IV criteria for unipolar depression (UP) and eight met the criteria for bipolar II disorder (BP II); in contrast, only two black patients met the criteria for unipolar depression and none met the criteria for BP II. Among patients diagnosed as BP I, Africans were significantly more likely than whites to show exclusively or mainly manic presentations while Afro-Caribbeans were more likely to have had mood-incongruent delusions. On the other hand, white patients were significantly more likely than Afro-Caribbeans to have had suicidal ideas or actions, and showed a similar but not significant excess when compared with Africans. Our findings could reflect either genuine ethnic differences in the presentation of severe affective disorder or be produced by the failure of British doctors to detect depression and deliver appropriate treatment to their black patients. The frequency with which Afro-Caribbean patients with mania present mood-incongruent delusions probably contributes to the high rates of diagnosed schizophrenia in this population.
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PMID:Ethnic differences in the presentation of bipolar affective disorder. 1057 48

Dermatoglyphic features are thought to be indicators of events in the early embryonal stages. They might also be associated with the developmental disorders of the central nervous system (CNS) including schizophrenia. Dermatoglyphic features of 92 male patients with bipolar affective disorder (BPAD) (unipolar depression and schizoaffective psychosis were excluded from the study) were compared with those of 195 males with schizophrenia (SCH) and both with those of 200 male controls (control group-CG). DSM-III-R criteria were used for the diagnostic evaluation. Quantitative analysis showed only one statistically significant difference between BPAD and SCH patients groups, regarding the c-d ridge count of the left hand. The canonical discriminant analysis did not permit correct classification (only 59.23% of cases were correctly classified) between BPAD and SCH. Numerous quantitative dermatoglyphic features of both BPAD and SCH differed significantly from those of the control subjects. Finger ridge counts as well as palmar ridge counts were markedly lower in BPAD and SCH as compared to the controls. These findings are not in contradiction with the hypothesis claiming that psychoses are a set of diverse expressions (due also to noninherited factors) of a single underlying entity.
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PMID:Dermatoglyphic analysis in bipolar affective disorder and schizophrenia--"continuum of psychosis" hypothesis corroborated? 1064 32

Neural cell adhesion molecule (N-CAM) is a cell recognition molecule, four major isoforms (180, 140, 120, and 105-115 kDa) of which are present in brain. N-CAM has several roles in cellular organization and CNS development. Previously we have found an elevation in CSF N-CAM 120 kDa in the CSF of patients with schizophrenia, bipolar disorder, and depression. We now report an increase in the variable alternative spliced exon (VASE), a 10 amino acid sequence inserted into the fourth N-CAM domain, in the CSF of patients with schizophrenia, but not in bipolar disorder or depression. VASE-immunoreactive (VASE-ir) bands were measured in CSF from patients with schizophrenia (n = 14), bipolar disorder I (n = 7), bipolar disorder II (n = 9), unipolar depression (n = 17) and matched controls (n = 37) by Western immunoblotting. Three VASE-ir bands were distinguished in lumbar CSF corresponding to heavy (165 kDa), medium (155 kDa) and low (140 kDa) MW. A logarithmic transformation was applied to the VASE protein units and analyzed with a MANOVA. There was a 51% and 45% increase in VASE heavy (p = 0.0008) and medium (p = 0.04) MW protein, respectively, in patients with schizophrenia as compared with normal controls. Current neuroleptic treatment in patients with schizophrenia had no effect on CSF VASE concentrations. VASE concentration correlated significantly with behavioral ratings in patients with schizophrenia but not affective disorders. Thus, VASE immunoreactivity is increased in schizophrenia but not in affective disorders. These results provide further evidence of an abnormality of N-CAM protein in chronic schizophrenia and suggest differences between schizophrenia and affective disorders in regulation of N-CAM.
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PMID:Elevated concentration of N-CAM VASE isoforms in schizophrenia. 1069 30

Dopamine neurotransmission has been implicated in the pathophysiology of schizophrenia and, more recently, affective disorders. Among the dopamine receptors, D3 can be considered as particularly related to affective disorders due to its neuroanatomical localization in the limbic region of the brain and its relation to the serotoninergic activity of the CNS. The possible involvement of dopamine receptor D3 in unipolar (UP) major depression was investigated by a genetic association study of the D3 receptor gene locus (DRD3) on 36 UP patients and 38 ethnically matched controls. An allelic association of DRD3 (Bal I polymorphism) and UP illness was observed, with the Gly-9 allele (allele '2', 206/98 base-pairs long) being more frequent in patients than in controls (49% vs 29%, P < 0.02). The genotypes containing this allele (1-2 and 2-2) were found in 75% of patients vs 50% of controls (P < 0.03, odds ratio = 3.00, 95% CI = 1.12-8.05). The effect of the genotype remained significant (P < 0.02) after sex and family history were controlled by a multiple linear regression analysis. These results further support the hypothesis that dopaminergic mechanisms may be implicated in the pathogenesis of affective disorder. More specifically, the '2' allele of the dopamine receptor D3 gene seems to be associated with unipolar depression and can be considered as a 'phenotypic modifier' for major psychiatric disorders.
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PMID:Association between the dopamine D3 receptor gene locus (DRD3) and unipolar affective disorder. 1069 26

Although neuropsychological studies have consistently reported executive deficits in schizophrenia, studies of executive functions in depression have produced equivocal results. The aim of this study was to examine the profile and the specificity of the executive impairment and its association with memory performance in young patients with unipolar depression. We compared patients with depression to normal control subjects and schizophrenics. Twenty young inpatients with unipolar depression, 14 schizophrenics and 20 age-, education- and IQ-matched control subjects were assessed with a neuropsychological battery including: (1) verbal memory task; (2) frontal tasks (WCST, Cognitive Estimate, Verbal fluency, verbal and visuo-spatial span) and a new complex sorting test (Delis test). Depressed patients and schizophrenics exhibited executive deficits. Unlike schizophrenics, depressed patients did not show memory impairment. Deficits in several 'higher-level' functions combined to produce executive impairments in patients with depression including complex integration for concept formation, spontaneous cognitive flexibility and initiation ability. Impaired functions in schizophrenia and in depressed patients were similar but were differently related to clinical variables. The pattern of memory failure in our schizophrenics is believed to reflect retrieval and encoding deficits. Our findings highlight the heterogeneity of skills grouped under the term 'executive functions' that are vulnerable in depression or schizophrenia.
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PMID:Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia. 1070 64


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