1Psychiatry Clin. Neurosci. 2003 Oct 57: 545-7
TitleMutation and association analysis of the DAP-1 gene with schizophrenia.
AbstractGlutamate dysfunction has been hypothesized to be involved in the pathophysiology of schizophrenia. The human homolog of Drosophila discs large protein (hDLG) and post-synaptic density-95-associated protein-1 (DAP-1) is one of the major proteins that are involved in intracellular signal transduction via N-methyl-d-aspartate receptors. In the present study 33 Japanese patients with schizophrenia were screened for mutations in the DAP-1 gene. A single nucleotide polymorphism was identified in the DAP-1 gene (1618A/G). A case-control study using a larger sample of unrelated patients and controls did not reveal a significant association between this polymorphism and schizophrenia. The results do not provide evidence that the DAP-1 gene is involved in vulnerability to schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
2Australas Psychiatry 2005 Sep 13: 253-7
TitleSurvey of depot antipsychotic prescribing in southern Adelaide.
AbstractDepot antipsychotic medication (DAP) is widely used in the treatment of schizophrenia and related disorders. The objectives of this study were to (i) determine whether DAP was being prescribed in accordance with established guidelines in terms of dose, interval of administration and indications; and (ii) assess the quality of the assessment and documentation of tardive dyskinesia (TD) as well as blood glucose and lipid abnormalities.
The survey was carried out between April and June 2003 at all three public hospital affiliated community mental health centres located in the southern region of Adelaide. Data were extracted from three sources: depot prescription charts, community mental health service case notes and hospital case notes.
Two hundred and sixty-one patients were receiving DAP. The majority (89%) had a diagnosis of schizophrenia or schizoaffective disorder. The DAP prescribed most frequently was zuclopenthixol decanoate (57%) at a modal dose of 200 mg and a modal administration interval of 2 weeks. Fifty-three per cent of patients had at least one dose reduction during the course of treatment. Four per cent of patients had a case note documented diagnosis of TD. Fifty-seven per cent of patients had at least one blood glucose test in the past year, with nearly half showing high results. Forty-seven per cent of patients had at least one lipid study in the past year, with more than half having high total cholesterol and 22% having high triglycerides.
The results of this study indicate that DAP is being used mostly for the treatment of schizophrenia and related disorders, which is in agreement with established evidence-based guidelines. The finding of at least one documented attempt at DAP dose reduction or extension of interval of administration in approximately half of the patients receiving DAP is encouraging and may have an impact on reducing the likelihood of TD. A formal TD surveillance programme using a screening tool such as the Abnormal Involuntary Movement Scale is recommended. In addition, more frequent evaluation of blood glucose and lipid levels is needed.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
3Bioorg. Med. Chem. 2015 Sep 23: 6195-209
Title1,4-Disubstituted aromatic piperazines with high 5-HT2A/D2 selectivity: Quantitative structure-selectivity investigations, docking, synthesis and biological evaluation.
AbstractSimultaneous targeting of dopamine D2 and 5-HT2A receptors for the treatment of schizophrenia is one key feature of typical and atypical antipsychotics. In most of the top-selling antipsychotic drugs like aripiprazole and risperidone, high affinity to both receptors can be attributed to the presence of 1,4-disubstituted aromatic piperazines or piperidines as primary receptor recognition elements. Taking advantage of our in-house library of phenylpiperazine-derived dopamine receptor ligands and experimental data, we established highly significant CoMFA and CoMSIA models for the prediction of 5-HT2A over D2 selectivity. Subsequently, the models were applied to identify the selective candidates 55-57 from our newly synthesized library of GPCR ligands comprising a pyrazolo[1,5-a]pyridine head group and a 1,2,3-triazole based linker unit. The test compound 57 showed subnanomolar a Ki value (0.64 nM) for 5-HT2A and more than 10- and 30-fold selectivity over the dopamine receptor isoforms D2S and D2L, respectively.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics
4Early Interv Psychiatry 2015 Jan -1: -1
TitleDuration of active psychosis and first-episode psychosis negative symptoms.
AbstractDuration of untreated psychosis (DUP) has been associated with negative symptoms in several studies; however, longitudinal findings have been inconsistent. No previous study has accounted for active psychosis after presentation, although this could impact on outcomes in a manner similar to DUP.
We measured Scale for the Assessment of Positive Symptoms at frequent intervals during the 12 months after initial presentation to determine the active psychosis duration for 230 individuals with first-episode psychosis. This duration was added to DUP prior to presentation to create a new variable, duration of active psychosis (DAP). Negative symptoms were divided into expressivity and motivation/pleasure domains as measured by Scale for the Assessment of Negative Symptoms (SANS). The relationship of DUP and DAP with negative symptoms at 24-month follow up was determined and confounders controlled for using regression analysis.
When DUP and DAP were compared as binary variables with long and short groups, 25.2% of individuals had differing category membership. DAP had a significant uncorrected association with both expressivity domain and motivation/pleasure domains at 24 months; however, relationship with DUP was not significant. DAP remained a significant predictor of 24-month expressivity domain after controlling for potential confounders.
Active psychosis after presentation is substantial, which is a limitation of DUP studies if active psychosis is considered as the key factor within DUP. DAP is a better predictor of negative symptoms than DUP at 2-year follow up, which suggests this concept requires further research.
SCZ Keywordsschizophrenia, schizophrenic, schizophrenics