Tratamiento de la enfermedad de Parkinson temprana / Treatment of early Parkinson's disease

RESUMEN La enfermedad de Parkinson (EP) es principalmente una enfermedad de pacientes ancianos. Es un trastorno multifacético que comprende síntomas motores y no motores en todas las etapas de la enfermedad. Esta revisión busca integrar los datos de las opciones de tratamiento más recientes con los datos de las terapias establecidas, a fin de proporcionar una referencia actualizada basada en la evidencia para los médicos que tratan la EP temprana, con medicamentos que puedan usarse como alternativa a la levodopa. El enfoque de los médicos para el tratamiento de la enfermedad de Parkinson (EP) temprana debe tener en cuenta numerosos aspectos, entre ellos, cómo informar al paciente sobre el diagnóstico y la decisión crítica de qué terapia adoptar y cuándo iniciarla. El tratamiento del trastorno motor asociado con la EP temprana debe considerar varios factores cruciales, como la edad de inicio, las comorbilidades y los requisitos funcionales del paciente, y no se puede resumir en una fórmula simple. En pacientes más jóvenes (es decir, antes de la edad de 70 años) y en aquellos sin altos requisitos funcionales, el tratamiento generalmente se inicia con agonistas de dopamina y / o inhibidores de la enzima monoaminooxidasa-B (MAO- B I). En pacientes más jóvenes, la levodopa se debe agregar a los agonistas de la dopamina y / o MAO-B I, según lo requiera la progresión de la enfermedad, mientras que en los pacientes mayores, cuando la respuesta a la levodopa sola no es satisfactoria, los agonistas de la dopamina o los inhibidores de la catecol-O- metiltransferasa pueden posteriormente ser agregados.

SUMMARY Parkinson's disease (PD) is primarily a disease of elderly patients. Is a multifaceted disorder comprised of both motor and non-motor symptoms at all stages of the disease. This review seeks to integrate data from the newest treatment options with data from established therapies, so as to provide an up-to- date evidence-based reference for clinicians treating early PD, with medications that can be used as an alternative to levodopa. The clinicians' approach to the treatment of early Parkinson's disease (PD) should take into account numerous aspects, including how to inform a patient upon diagnosis and the critical decision of what therapy to adopt and when to start it. The treatment of the motor disorder associated with early PD needs to consider several crucial factors, such as age at onset, comorbidities, and the patient's functional requirements, and cannot be summarized in a simple formula. In younger patients (i.e., before the age of 70) and in those without high functional requirements, treatment is usually initiated with dopamine agonists and/or monoamine oxidase-B enzyme inhibitors (MAO-B I). In younger patients, levodopa should be added to dopamine agonists and/or MAO-B I, as required by disease progression, whereas in older patients, when response to levodopa alone is not satisfactory, dopamine agonists or catechol-O- methyltransferase inhibitors may subsequently be added.

Correlation of catechol-O-methyl transferase Vall58Met polymorphism with prepulse inhibition of the auditorystartle reflex in patients with schizophrenia / 中国心理卫生杂志

Objective:To investigate the association between catechol-O-methyl transferase (COMT)Vall58Met polymorphism and prepulse inhibition of the auditory startle reflex (PPI) in patients with schizophrenia.Methods:Totally 178 patients with schizophrenia and 190 healthy volunteers were recruited.The auditory startle reflex was detected by using SR-HLAB monitoring system.The indexed of the auditory startle reflex included the amplitude,habituation％ and PPI30,PPI60,PPI120 (the lead interval was set 30 ms,60 ms,120 ms).COMT Vall58Met polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP).The differences of PPI among COMT genotypes were compared.Results:Compared to the healthy volunteers,patients with schizophrenia had a significant lower the amplitude of auditory startle reflex[(563± 460) mV vs (695 ± 447) mY,P ＜ 0.05] and habituation％ [(32 ± 46) vs (48 ± 33),P ＜ 0.01] as well as the ％PPI120[(27 ± 5) vs (35 ± 3),P ＜ 0.05].The significant differences in COMT allelic and genotypic distribions were observed between patients with schizophrenia and healthy volunteers (x2 =8.16,11.74,Ps ＜ 0.05).The significant main effect of COMT genotype on habituation％ was observed (P ＜0.05) but no interaction genotype by diagnosis on the amplitude of auditory startle reflex,habituation％ and ％ PPI120 was observed (Ps ＞ 0.05).Conclusions:There may be a correlation between COMT genotype and adaptability,but not between COMT genotype and PPI deficit present in patients with schizophrenia

The association of catechol-O-methyl transferase gene polymorphism with the clinical efficacy of risperidone in the treatment and cognitive function in patients with schizophrenia / 中华行为医学与脑科学杂志

Objective To investigate the relationship between the catechol-O-methyl transferase (COMT) gene polymorphism and the clinical efficacy and cognitive function of risperidone in the treatment of schizophrenia.Methods 105 cases of Han Chinese patients with schizophrenia who were treated with risperidone for 12 weeks and healthy controls of 168 cases were collected.The effect of the drug therapy with the PANSS,digit vigilance test,Raven Standard Progressive Matrices,forward and backward subtests of the digit span test were evaluated,and then the rs 165599,rs4680,rs6267,rs737865 loci in COMT gene were detected.Results (1)rs737865 was not the polymorphic locus in this sample.(2) There was statistically significant between schizophrenia patients and controls in the distribution of allele frequency and genotype frequency in rs4680 (x2=8.16,P=0.02).Haplotype GA in rs165599-rs4680 was statistically significant in schizophrenia patients and controls (x2 =4.35,P =0.04).(3) After treatment,the total score ((47.64±5.75) points),subscale scores (positive symptoms (11.66±2.90) points,negative symptoms (13.79±3.18)points,general psychotic symptoms (22.09±3.59) points) and scores of five factors model in PANSS decreased and the difference was significant (P＜0.05);the scores of digital cancellation test increased significantly compared with those before treatment(t value respectively were 12.34,10.17,4.34,all P＜0.05);the scores of forward and backward subtests of the digit span test were significantly increased compared with those before treatment (t=-5.57,P=0.00) and Raven standard reasoning test scores had increased significant (t=-19.05,P=0.00).(4) The difference of instantaneous memory score changes among rs 165599 genotypes was statistically significant after treatment (F=4.06,P=0.02).(5) The difference of negative syndromes of PANSS among rs 165599 genotypes was statistically significant after treatment (F=3.11,P=0.049).(6) The difference of negative symptoms (F=4.64,P=0.01),cognitive impairment (F=3.21,P =0.045) and instantaneous memory (F=4.86,P=0.03) among rs 6267 genotype were statistically significant after treatment.Condusion Risperidone can effectively improve the psychotic symptoms of schizophrenia patients,and promote the recovery of cognitive function.Rs165599-rs4680 haplotype GA might be risk factor for the onset of schizophrenia.

Effect of Polymorphisms of Three Genes Mediating Monoamine Signalling on Brain Morphometry in Schizophrenia and Healthy Subjects

OBJECTIVE: We examined the effect of risk alleles of polymorphisms of three schizophrenia risk genes that mediate monoamine signalling in the brain on regional brain volumes of schizophrenia and healthy control subjects. The risk alleles and the gene polymorphisms studied were: Val allele of catechol o-methyltransferase (COMT) rs4680 polymorphism; short allele of 5-hydroxy tryptamine transporter linked polymorphic region (5HTTLPR) polymorphism; and T allele of 5-hydroxy tryptamine 2A (5HT2A) rs6314 polymorphism. METHODS: The study was carried out on patients with recent onset schizophrenia (n=41) recruited from the outpatient department of National Institute of Mental Health and Neurosciences, Bangalore, India and healthy control subjects (n=39), belonging to South Indian Dravidian ethnicity. Individual and additive effects of risk alleles of the above gene polymorphisms on brain morphometry were explored using voxel-based morphometry. RESULTS: Irrespective of phenotypes, individuals with the risk allele T of the rs6314 polymorphism of 5HT2A gene showed greater (at cluster-extent equivalent to family wise error-correction [FWEc] p<0.05) regional brain volumes in the left inferior temporal and left inferior occipital gyri. Those with the risk alleles of the other two polymorphisms showed a trend (at p<0.001, uncorrected) towards lower regional brain volumes. A trend (at p<0.001, uncorrected) towards additive effects of the above 3 risk alleles (subjects with 2 or 3 risk alleles vs. those with 1 or no risk alleles) on brain morphology was also noted. CONCLUSION: The findings of the present study have implications in understanding the role of individual and additive effects of genetic variants in mediating regional brain morphometry in health and disease.

Correlation study on susceptible genes of obsessive compulsive disorder of Han population in northeast China / 中华行为医学与脑科学杂志

Objective To explore the relationship between Monoamine oxidase A (MAOA) receptor gene,catechol-O-methyltransferase (COMT) receptor gene,dopamine D3 receptor(DRD3) gene and 5-HT2C receptor gene(5-HT2c) of Han population in northern China and obsessive compulsive disorder.Methods Polymerase chain reaction amplification determination of MAOA-T1460C,COMT-Val158Met,DRD3-Ser9Gly,5-HT2c-C ys23Ser four loci receptor gene polymorphism in 164 patients with OCD patients including 103 core pedigrees of fragment length polymorphism,and association and linkage disequilibrium (TDT)analysis.Results There was no significant difference of MAOA-T1460C,COMT-Val158Met,DRD3-Ser9Gly,5-HT2c-Cys23Ser four receptor gene in the patient group and the control group of genotype and allele distribution difference(P＞0.05),four receptor gene loci were in accordance with the balance of the H-W,the MAOA-T1460C receptor gene in female patients group and control group,the early group and control group,which has forced thinking and difference of compulsive behavior group and the control group,only the obsessional group and the control group of genotype and allele distribution was statistically significant(P＜0.05),and the family group between chain(P=0.0001) ;5-HT2c-Cys23Ser receptor gene in the case group and the control group,male both forced thinking and compulsive behavior group and control group differences in genotype and allele distribution was statistically significant (P＜ 0.05),and between family groups exist chain (P=0.0389) ; COMT-Val158Met receptor gene in the control experiments were no significant difference(P＞0.05),and with the house group does not exist between the chain (P=0.0622) ;DRD3-Ser9Gly receptor gene in the control experiments were no significant difference(P＞0.05),and with the family groups there is no chain(P=0.1101).Conclusion MAOA-T1460C receptor gene polymorphism and 5-HT2c-Cys23Ser receptor gene polymorphisms may be the susceptible gene of obsessive compulsive disorder.

Impact of COMT H108L, MAOB int 13 A>G and DRD2 haplotype on the susceptibility to Parkinson’s Disease in South Indian subjects.

In view of documented evidence demonstrating the association of dopaminergic metabolism and neurotransmission with Parkinson’s disease (PD), a case-control study was conducted to investigate the impact of particular polymorphisms in the catechol O-methyl transferase (COMT) H108L, monoamine oxidase B (MAOB) int 13 A>G, dopamine transporter 1 (DAT1) A1215G, dopamine receptor D2 (DRD2) Taq1A, DRD2 Taq1B and DRD2 Taq1D genes on the susceptibility to PD. PCR-RFLP method was used for the genetic analysis. The COMT H108L polymorphism increased PD risk by 1.4-fold (95%CI: 1.02-1.98), whereas reduced risk was observed with MAOB int 13 A>G polymorphism (OR: 0.77, 95%CI: 0.51-0.99). Multifactor dimensionality reduction analysis showed gene-gene interactions between these two loci that resulted in loss of the protective role of MAOB G-allele in the presence of COMT L-allele. DAT1A1215G polymorphism in the exon 9 was not associated with PD. Individually, DRD2 polymorphisms showed null association. However, all-variant haplotype of DRD2 locus i.e. T-G-T haplotype showed 29.8-fold risk for PD compared to all-wild haplotype i.e., C-A-C haplotype (95%CI: 6.85-130.4). To conclude, genetic variants of COMT, MAOB and DRD2 loci modulate susceptibility to PD in South Indian subjects.

An association study on Gilles de la Tourette's syndrome and catechol-O-methyl transferase gene polymorphism / 中华行为医学与脑科学杂志

ObjectiveTo investigate the association between catechol-O-methyl transferase (COMT)gene polymorphism and Gilles de la Tourette' s syndrome(GTS).MethodsUsing Amplification Refractory Mutation System(ARMS) PCR genotyping assay method,a polymorphism (val158met) of COMT gene was genotyped in 112 of all GTS patients ( total GTS group) including 54 GTS-alone patients group,48 GTS + ADHD patients group among of them and 71 healthy controls.The correlation between positive association of polymorphism (val158met)of COMT gene in GTS and the age of onset in patients with GTS was also analyzed.ResultsCompared with healthy controls group,genotype of val158met did not differ in total GTS patients group or alone-GTS patients group (χ2 =0.56,P=0.756;χ2 =1.05,P=0.600 respectively).There was also no significant difference (P＞0.05)in allele distribution of val158met in total GTS patients group or alone-GTS patients group compared with controls group respectively (χ2 =0.18,P=0.669;χ2 =0.29,P=0.593 respectively).However,genotype distribution of val158met was significantly different between GTS + ADHD patients group and controls group( χ2 =6.35,P =0.041 ).The frequency of the val allele of this locus was significantly higher in GTS + ADHD patients group than those in controls group ( χ2 =5.49,P =0.019 ).The mean age of onset (6.80 ± 1.54 ) in 36 children within GTS + ADHD patients group with the val/val geantype of COMT gene val158met polymorphism was significantly earlier than the mean age of onset (8.04 ± 1.54)in 12 children in val/val genotype (P =0.016 ).ConclusionPolymorphism (val158met) of COMT gene may be associated with GTS children with comorbid ADHD,which may play an important role to make the age of onset in children with GTS become earlier.

No Association between Val108/158Met Polymorphism on Catechol-O-Methyl Transferase(COMT) Gene and Smooth Pursuit Eye Movement(SPEM) Abnormality in Korean Schizophrenia Patients

OBJECTIVES: We investigated the association of Val108/158Met polymorphism on catechol-O-methyl transferase(COMT) gene with smooth pursuit eye movement(SPEM) abnormality in Korean schizophrenia patients. METHODS: We measured SPEM in 217 Korean schizophrenia patients(male 116, female 101) and divided them into two groups, one was a good SPEM function group and the other was a poor SPEM function group. Then we analyzed Val108/158Met polymorphism on COMT gene. We compared the differences of genotype and allele distributions of the polymorphism on COMT gene between the two groups. RESULTS: The natural logarithm value of signal/noise ratio(Ln S/N ratio) of the good SPEM function group was 4.39+/-0.33(mean+/-s.d.) and that of poor SPEM function group was 3.17+/-0.71. There were no statistically significant differences of age and male/female ratio between the two groups. There were no significant differences of genotype or allele distributions of the Val108/158Met polymorphism on COMT gene between the two schizophrenic groups. CONCLUSIONS: The results suggest that Val108/158Met polymorphism on COMT gene is not related to SPEM function abnormality in schizophrenia.