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)

We present a case of acute myeloid leukemia (AML-M2) with trisomy 5 (+5) as the sole cytogenetic abnormality in a woman previously diagnosed with schizophrenia. To date, only two cases of AML (other than M2) with +5 as the only change have been reported. Moreover, an association between schizophrenia and partial trisomy of chromosome 5p has been described recently. To our knowledge, this is the first report of AML (subtype-M2) with +5. Noteworthy is the association with schizophrenia.
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PMID:A new case of trisomy 5 as sole cytogenetic anomaly in acute myeloid leukemia. 853 25

Loci conferring susceptibility to schizophrenia, coeliac disease, and orofacial clefting have been assigned to the 6p23-p25 region of human chromosome 6. To facilitate the identification of candidate genes we have sublocalized and ordered 39 ESTs assigned to this interval by radiation hybrid mapping. This was achieved by generating PAC contigs containing the ESTs, genetic markers, and random STSs. For full integration into previously published data a single YAC contig spanning 6p23-p25 was used to unambiguously order the PAC contigs and ESTs along the chromosome. The majority of the ESTs (31/39) were positioned in the 6p23-p24 interval at the proximal half of the map, and of these 8 are located within a single PAC clone. The order of known genes in this region is cen-CD83-ZNF40-EDN1-(GCNT2, CAPZB)-TFAP2-BMP6-DSP-tel.
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PMID:Fine mapping of 39 ESTs on human chromosome 6p23-p25. 941 21

The aim of the study is to validate the etiological role of KIAA0027/MLC1 in childhood-onset megalencephalic leukoencephalopathy with subcortical cysts (MLC) and in schizophrenia, particularly the catatonic subtype, which were reported to be allelic diseases. Among a series of five patients with MLC, four mutant alleles were detected: one case of compound heterozygosity for a splice site mutation and a six-base-pair in-frame deletion, one patient with a homozygous frameshifting insertion-deletion, and a further case heterozygous for a A157E substitution. A systematic mutation screening in 140 index cases with schizophrenia revealed 13 different single nucleotide polymorphisms (SNPs): one SNP in the 5'-UTR, seven SNPs in intronic regions, two synonymous codon variants (T52, Y199), and three coding variants. Two of them, C171F and N218K, were observed in controls at a significant frequency. The L309M variant that was previously supposed to be the causative factor for chromosome 22q(tel) linked-periodic catatonia was found nonsegregating in a further multiplex pedigree. Furthermore, a complicated 33-bp insertion/deletion polymorphism at the 5'-end of exon 11 of MLC1 was found at equal frequency among schizophrenic patients and controls. In summary, our study provides further evidence for allelic heterogeneity in megalencephalic leukoencephalopathy, excludes MLC1 as a susceptibility locus for schizophrenia, and thereby rules out that MLC and schizophrenia are allelic disorders.
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PMID:Sequence diversity of KIAA0027/MLC1: are megalencephalic leukoencephalopathy and schizophrenia allelic disorders? 1249 30

Since 1980s there is a noticeable change in the homeless population in Western countries. Some researchers titled the change as the "new" homeless that are distinctly different than the "skid row" population described in the past. Among the "new" homeless there are increasing numbers of elderly subjects. The elderly homeless are a fragile and vulnerable group that suffers from high rates of physical and mental problems as well as increased mortality. The aim of the present study was to characterize the "new" elderly homeless. Over a 10-year period each homeless 65 years of age and older was assessed by a psychiatrist. The project was undertaken in Tel-Aviv, Israel, and was feasible due to close co-operation between the Municipal Welfare Department and mental health consultants. The Structured Clinical Interview for DSM-IV (SCID) was the main diagnostic tool. Ninety-eight subjects of 2567 homeless persons located and contacted were elderly (3.8%). Mean age for the elderly sub-group was 71.7+/-5.3 years and the great majority were male 94/98 (95.9%). In 44/98 (44.9%), a formal DSM-IV axis I psychiatric disorder was diagnosed, most common being dementia (15/44) and schizophrenia (15/44). A significant minority of 13/44 (29.5%) were diagnosed and treated prior to becoming homeless. Physical co-morbidity was found in nearly 2/3 subjects. Following intensive case-management by social workers, 35/44 (79.5%) subjects were successfully placed in permanent housing. The main conclusion is that the "new" elderly homeless are typically males suffering from frequent psychiatric morbidity and physical co-morbidity. Intensive case-management succeeded in achieving return to permanent housing in the majority of subjects.
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PMID:Characterizing the elderly homeless: a 10-year study in Israel. 1288 28

Data on admissions of schizophrenia- and schizoaffective disorder patients to Tel-Aviv's seven public psychiatric hospitals during 11 consecutive years were obtained along with relevant meteorological information. Mean monthly admission rates were significantly higher during the summer (for schizophrenia patients) and fall (for schizoaffective patients). Schizophrenia patients' mean monthly admission rates correlated with mean maximal monthly environmental temperature (R = 0.35, N = 132 months, P <0.001). The present study may indicate that persistent high environmental temperature may be a contributing factor for psychotic exacerbation in schizophrenia patients and their consequent admission to mental hospitals.
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PMID:Effects of climate on admission rates of schizophrenia patients to psychiatric hospitals. 1564 46

In schizophrenia, a psychiatric disorder that affects approximately 1% of the global population and is associated with substantial disability, a significant proportion of patients (usually estimated to be at least 30%) fail to respond to treatment, and many patients have difficulty continuing treatment because of side effects. At the time of publication, all available medications for schizophrenia targeted dopamine and other monoamine neurotransmitters. However, a substantial amount of research suggests that patients with schizophrenia have underlying deficits within the GABA neurotransmitter system. BL-1020, being developed by BioLineRx Ltd under license from Tel Aviv University Ltd and Bar-Ilan Research & Development Co Ltd, is a novel compound consisting of the well-established antipsychotic drug perphenazine and GABA. Preclinical studies of BL-1020 indicated that the compound penetrated the brain and was efficacious in rodents, with a significant reduction in side effects compared with the administration of perphenazine. BL-1020 was well tolerated in all clinical trials conducted, and clinically meaningful improvements were demonstrated in phase II trials in patients with schizophrenia. Further data from phase II and subsequent phase III trials will be required to derive conclusions for BL-1020 regarding overall efficacy.
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PMID:BL-1020, an oral antipsychotic agent that reduces dopamine activity and enhances GABAA activity, for the treatment of schizophrenia. 2004 63

Glutamatergic and dopaminergic neurotransmission is modulated by adenosine, whose ambient level in the brain is in turn regulated by the metabolic enzyme, adenosine kinase (ADK). Brain adenosinergic tone can therefore be effectively reduced and increased by up- and down-regulation of ADK expression, respectively. Although changes in brain ADK levels can yield multiple behavioral effects, the precise functional significance of telencephalon (neocortical and limbic structures) adenosine remains ill-defined. Among the phenotypes identified in transgenic mice with brain-wide ADK overexpression (ADK(TG) mice) and reduced adenosinergic tone, working memory deficiency and potentiated response to systemic N-methyl-d-aspartate receptor blockade were exacerbated by the introduction of local ADK disruption (elevated adenosinergic tone) restricted to the telencephalon (ADK(TG):ADK(Tel-def) mice). These two phenotypes, which are central to schizophrenia cognitive/negative symptoms, appear to be regulated by adenosinergic activities within and outside the telencephalon in a complementary manner. Here, we extended this unique comparison between ADK(TG) mice ADK(TG):ADK(Tel-def) mice to another prominent phenotype previously documented in ADK(TG) mice - namely, impaired Pavlovian conditioned freezing. We found that ADK(TG):ADK(Tel-def) mice again were associated with a more severe phenotype while sharing a similar phenotype profile. Furthermore, we qualified that this Pavlovian phenotype did not translate into a general deficiency in associative learning, since no such deficit was evident in three other (aversive and appetitive) Pavlovian learning paradigms. The present study has thus identified a hitherto unknown function of brain adenosine: the execution of conditioned freezing behavior, which is dependent on the balance of adenosinergic changes between the telencephalon and the rest of the brain.
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PMID:Dysregulation of brain adenosine is detrimental to the expression of conditioned freezing but not general Pavlovian learning. 2329 Sep 37

Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12-40) and Tel Aviv (TLV; n=59, aged 12-36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations.
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PMID:Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts. 2720 Apr 94

About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N=171) and typically developing (TD; N=832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N=21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N=129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR=3.90, 95% CI=1.34-11.34) or IDD (OR=5.05, 95% CI=3.01-10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms.
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PMID:Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study. 2804 19