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Tardive dyskinesia (TD) is a difficult-to-treat condition. The presence of genetically abnormal D2 and D3 dopamine receptors is associated with increased like hood of TD in patients with schizophrenia. We present a case of a patient with TD and genetically abnormal dopamine D3 receptors with chronic schizophrenia, treated successfully by sertindole.
Methods
A 47-year old male with history of chronic chizophrenia was assessed clinically by means of SCID IV, PANSS and AIMS, and was genotyped for DRD3ser-gly and 5-HT2C receptor gene polymorphisms.
Results
The patient suffered from an exacerbation of positive and negative psychotic symptoms and TD. He was also found to be DRD3ser-gly heterozygous. He had been suffering from TD for two years, developed by chronic administration of haloperidole and resperidone. A trial with quetiapine failed to ameliorate his TD and psychotic symptoms, whereas a successive trial with clozapine induced life-treating hematological side effects. After the administration of sertindole (16mh/day) his psychotic and TD symptoms remitted (PANSS:29, AIMS : 0). One year later his level of improvement was wholly preserved.
Conclusion
Sertindole might be beneficial for the treatment of TD in patients who have genetically abnormal D3 receptors.
Modafinil improves the residual excessive daytime sleepiness (EDS) in patients who remain sleepy despite nCPAP therapy however, its effects on cognitive performance in this group of OSA patients have been equivocal. In the present study we examined the effects of a single modafinil dose on cognitive performance in newly diagnosed OSA patients, prior to the onset of nCPAP therapy.
Methods:
Twelve unmedicated patients recently diagnosed with Obstructive Sleep Apnea (OSA) following polysomnography, entered into a double-blind, randomized, placebo-controlled crossover study using a single 200 mg dose of modafinil. The Cambridge Neuropsychological Test Automated Battery (CANTAB) and Visual Analogue Scales (VAS) were used.
Results:
Consistent with its alerting effects, modafinil increased VAS-rated alertness and improved visual and sustained attention (CANTAB Reaction Time Tests and RVIP). There was a trend for improvement in VAS-rated mood and anxiety. Modafinil improved problem solving performance (CANTAB Stockings of Cambridge) which was accompanied by prolonged thinking times. A similar pattern of improvement with improved recall coupled by prolonged response times was seen in the CANTAB Delayed Matching-To-Sample test of visual memory.
Conclusions:
This modafinil-induced alteration in the speed-accuracy trade-off has been previously seen in healthy subjects and adults with ADHD and indicates that modafinil increases the ability to “reflect” on problems coupled with decreased impulsive responding. If these benefits are shown to be maintained with chronic administration, modafinil may have potential as an important therapy for OSA patients with residual EDS following nCPAP therapy.
Recent studies support an important role of microRNAs in cancer and major psychiatric disorders, through their regulotory role on the expression of multiple genes. The low incidence of cancer in patients with schizophrenia as a comorbidity status, is an old hypothesis which needs further investigation mainly on microRNAs function, through their oncosupressive or oncogenic activity, in the development of psychiatric disorders.
Material and Methods
The expression pattern of a variety of different was investigated in a sample of patients suffering from schizophrenia (n=6), in a another sample wit a solid tumor (n=10) and in a sample of patients with both schizophrenia and tumor (n=8). MiRNAs analysis was performed in whole blood samples using the miRCURY LNA TM microRNA Aray technology.
Results
A number of 3 microRNAs showed a statistically significant differential expression between the 3 groups. Specifically, significant down-regulation of the let-7p-5p, miR-98-5p and miR-183-5p in the study groups of tumor alone and and tumorand schizophrenia.
Conclusions
The results of the present study that let-7, miR-98 and miR-183 might play an important oncosuppressive role through their regulatory impact in gene expression irrespective of the presence of schizophrenia. Further studies are warranted in order to investigate of these and other mico-RNAs in the molecular pathways of schizophrenia and of other major psychiatric disorders.