Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolcapone is a catechol-O-methyltransferase (COMT) inhibitor that has shown efficacy in the treatment of Parkinson's disease. The authors undertook the first study on the efficacy of this COMT inhibitor in the treatment of major depressive disorder (MDD). The authors also wanted to assess the effects of tolcapone on the choline and myoinositol resonances in the left caudate and dorsolateral frontal lobe through proton magnetic resonance spectroscopy and on whole blood levels of S-adenosyl-L-methionine (SAMe). The study enrolled 21 adults (10 men and 11 women; mean age, 42.6 +/- 9.6 years) with MDD, which was diagnosed using the Structured Clinical Interview for DSM-IV, and an initial score of > or = 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). Patients were then treated openly for 8 weeks with tolcapone 400 mg twice daily. Treatment efficacy was assessed with the HAM-D-17, the Clinical Global Impressions Severity (CGI-S) scale, and the Beck Depression Inventory (BDI). Among all subjects (N = 21), there were significant (p < .0001) decreases at endpoint in HAM-D-17 scores (from 19.4 +/- 2.9 to 10.7 +/- 5.5), CGI-S scores (from 3.9 +/- 0.6 to 2.4 +/- 1.1), and BDI scores (from 21.6 +/- 8.1 to 12.3 +/- 8.6). Eight patients (38%) dropped out before completing the 8-week open study because of diarrhea, elevated liver function tests, increased anxiety, and noncompliance. No significant effects were noted on choline and myoinositol resonance or on SAMe levels in whole blood before and after 2 weeks of tolcapone treatment. The preliminary results suggest that tolcapone may be a promising agent in the treatment of MDD. Furthermore, double-blind, placebo-controlled studies are necessary to confirm this impression.
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PMID:Open study of the catechol-O-methyltransferase inhibitor tolcapone in major depressive disorder. 1077 Apr 81

Attention deficit hyperactivity disorder (ADHD) is a developmental syndrome expressed along three domains: inattention, hyperactive-impulsive, and combined type. Both environmental and genetic factors contribute to the etiology of this complex disease. In the current investigation, a catechol-O-methyltransferase (COMT) polymorphism that codes for a high versus low enzyme COMT activity was examined using family-based methods for a role in ADHD. Using a haplotype relative risk design and a parent-to-proband allele transmission test with 48 ADHD triads, we found an association between COMT and illness (chi(2) = 4.72, p = 0.03, df = 1). In particular, the impulsive-hyperactive type of ADHD (excluding inattention) ascertained by Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria (chi(2) = 8.34, p = 0.004, df = 1), by the Conners Teaching Rating Hyperactivity scale (Pearson chi(2) = 5.32, p = 0.02, df = 1) as well as by the Continuous Performance Test False Alarm scale (chi(2) = 2.78, p = 0.096, df = 1) were associated with the high enzyme activity COMT val allele. Similar results were obtained if genotype frequencies were compared. It should be noted that the association between the high-enzyme activity COMT val allele that increases CNS dopamine (and norepinephrine) clearance is consistent with the use of methylphenidate, an agent that increases dopamine (and norepinephrine) turnover, in the treatment of this disorder. These provisional findings suggest that newly developed COMT inhibitors such as tolcapone, applied in Parkinson's disease, might in due time be considered in the treatment of ADHD.
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PMID:Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): association of the high-enzyme activity Val allele with ADHD impulsive-hyperactive phenotype. 1049 Jul 6

To assess if a specific lesion pattern or changes of the basal limbic system as seen in primary depression and depression associated with neurodegenerative disorders might be identified in depressive multiple sclerosis (MS) patients, we submitted 78 MS patients to a MRI examination consisting of a quantitative measurement of lesions and of hyperintense signals from the pontomesencephalic midline (raphe). Furthermore relaxometry of the pontomesencephalic midline, a transcranial ultrasound examination rating its echogenicity semiquantitatively and a standardized neurological, neuropsychiatric and neuropsychological assessment were obtained. Thirty-one patients fulfilled the DSM-IV criteria for depression. Depressed MS patients had a significantly larger temporal lesion load than non-depressed MS patients, especially on the right side. A trend of difference was detected for lesions of the right parietal lobe, the right frontal lobe, the cerebellum and the total lesion load. Neither hyperintense signals or relaxometry nor echogenicity of the region at the level of the pontomesencephalic midline were significantly different between the groups. We conclude that depression in MS patients is not associated with an alteration of the basal limbic system at the brainstem as seen in Parkinson's disease or unipolar depression but with an increased lesion load of the projection areas of the basal limbic system.
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PMID:Lesion pattern in patients with multiple sclerosis and depression. 1087 26

The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Asberg Depression Rating Scale (MADRS) against the DSM-IV diagnosis 'depressive disorder' was assessed in patients with Parkinson's disease (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the outpatient department of an academic hospital were diagnosed according to a standardised research protocol. This protocol consisted of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or absence of 'depressive disorder' according to the DSM-IV criteria, as well as the HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves) were obtained and the positive and negative predictive values (PPV, NPV) were calculated for different cut-off scores. Maximum discrimination between depressed and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD-17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and 14/15 for the MADRS, the high sensitivity and NPV make these scales good screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and 17/18 for the MADRS, the high specificity and PPV make these instruments good diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly better than that of the MADRS. This study shows that it is justified to use the HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize patient samples into depressed and non-depressed groups.
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PMID:The validity of the Hamilton and Montgomery-Asberg depression rating scales as screening and diagnostic tools for depression in Parkinson's disease. 1091 46

Parkinson's disease (PD), that has usually been associated with movement disorders, is also associated with depression in about 40% of patients [1-9]. Transcranial magnetic stimulation (TMS) is a new non-invasive technique for direct stimulation of the cerebral cortical neurons [1]. Several open studies have shown that repetitive TMS (rTMS) at both rapid (rapid rTMSi > 1 Hz) and low frequencies (slow rTMSi < 1 Hz) may have antidepressant action [2-6]. The study included 8 patients diagnosed as PD fulfilling the DSM-IV criteria for major depression (5 patients) and dysthymia (3 patients). Magnetic stimulator, 200 Mag-Stim, total output 2 T and a circular coil of 90 mm, were used. For ten consecutive days, between noon and 1 p.m. the patients were stimulated with apprx. 80% of the output (1.6 T) at 0.5 Hz. The daily treatment implied stimulation of both sides of the head (first the right, then the left) at four sites (prefrontal, frontal, parietal and occipital regions) with 5 stimulations each site (20 stimulations per hemisphere). Before the beginning of the study, 2-3 hours after the last stimulation (day 10), 7 and 14 days after completion of the treatment, the patients were subjected to scoring on the Hamilton Depression Rating Scale [11] and Unified Parkinson's Disease Rating Scale (UPDRS) [12]. The HDRS values before initiation of rTMS were 19.2 +/- 3.1, with significant fall (p < 0.01) after 10 days of stimulation (14.9 +/- 3.2), 17 days (12.2 +/- 2.7) and 24 days (13.6 +/- 5.3) after the beginning of the study, suggesting that the antidepressive effect persisted even two weeks after discontinuation of stimulation. The UPDRS values were monitored concomitantly. The values on this scale failed to alter significantly. In conclusion, rTMS is a relatively safe and painless method associated with antidepressant action in PD patients. Treatment of depression in PD is of great importance, but the choice of medication is accompanied with numerous limitations [20]. Antidepressant action of rTMS and its maintenance for two weeks after discontinuation of stimulation enables usage of this method in PD in phases of exacerbation of depressive symptoms at least over the period required to reach the full effect of selected medication.
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PMID:[Effect of slow repetitive transcranial magnetic stimulation on depression in patients with Parkinson disease]. 1153 77

There are several problems related to the diagnosis and the biochemical background of depression in patients with Parkinson's disease (PD). The most important problem is how do we understand depression in PD. According to surveys using the diagnostic procedures specified in the Diagnostic Statistic Manual-III or IV, the prevalence of depression is 20-40% in PD. However, the reported rate varies according to the composition of the subject group and whether or not a control group is used, so it is still controversial whether a figure of 20-40% reflects the actual prevalence of depression. Latest studies showed about 2-8% of PD patients are diagnosed with major depression by DSM-III-R. These recent studies suggest that major depression and PD may coexist and dysthimic disorder may be an essential feature in PD. With regard to the neurochemical background, the level of 5-hydroxyindoleacetic acid (a major metabolite of serotonin) is reduced in the cerebrospinal fluid suggesting that serotonergic dysfunction exists in the brain of PD patients. However, there is no high quality evidence to indicate the effectiveness of selective serotonin reuptake inhibitors for depression in PD. Autopsy studies have revealed that not only serotonin, but also dopamine, noradrenaline and other neurotransmitters are reduced in the brains of patients with PD. Accordingly, treatment may become difficult in many cases due to these changes of multiple neurotransmitters. Development of a better treatment strategy based on improved understanding of the neurochemical background is needed.
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PMID:Depression in Parkinson's disease: its prevalence, diagnosis, and neurochemical background. 1169 89

Parkinson's disease (PD), that has usually been associated with movement disorders, is also associated with depression in about 40% of patients [9]. Transcranial magnetic stimulation (TMS) is a new non-invasive technique for direct stimulation of the cerebral cortical neurons [1]. Several open studies have shown that repetitive TMS (rTMS) at both rapid (rapid rTMSi: > 1 Hz) and low frequencies (slow rTMSi: < 1 Hz) may have antidepressant action [2-6]. The study included 8 patients diagnosed as PD fulfilling the DSM-IV criteria for major depression (5 patients) and dysthymia (3 patients). Magnetic stimulator, 200 Mag-Stim, total output 2 T and a circular coil of 90 mm, were used. For ten consecutive days, between noon and 1 p.m. the patients were stimulated with apprx. 80% of the output (1.6 T) at 0.5 Hz. The daily treatment implied stimulation of both sides of the head (first the right, then the left) at four sites (prefrontal, frontal, parietal and occipital regions) with 5 stimulations each site (20 stimulations per hemisphere). Before the beginning of the study, 2-3 hours after the last stimulation (day 10), 7 and 14 days after completion of the treatment, the patients were subjected to scoring on the Hamilton Depression Rating Scale [11] and Unified Parkinson's Disease Rating Scale (UPDRS) [12]. The HDRS values before initiation of rTMS were 19.2 +/- 3.1, with significant fall (p < 0.01) after 10 days of stimulation (14.9 +/- 3.2), 17 days (12.2 +/- 2.7) and 24 days (13.6 +/- 5.3) after the beginning of the study, suggesting that the antidepressive effect persisted even two weeks after discontinuation of stimulation. The UPDRS values were monitored concomitantly. The values on this scale failed to alter significantly. In conclusion, rTMS is a relatively safe and painless method associated with antidepressant action in PD patients. Treatment of depression in PD is of great importance, but the choice of medication is accompanied with numerous limitations [20]. Antidepressant action of rTMS and its maintenance for two weeks after discontinuation of stimulation enables usage of this method in PD in phases of exacerbation of depressive symptoms at least over the period required to reach the full effect of selected medication.
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PMID:[Effect of slow repetitive transcranial magnetic stimulation on depression in patients with Parkinson 's disease]. 1192

This review examines the frequency of depression complicating Parkinson's disease (PD), its aetiology and clinical features, and also how it may be recognised and treated. Studies investigating the frequency of depression in PD have yielded figures ranging between 2.7% and 70%. Methodological differences account for much of the disparity. The aetiology of depression in PD is complex, and probably relates to both biological and exogenous factors. Dysfunction of multiple neurotransmitter systems, including the serotonergic system, may be involved. Mood disturbances resulting from deep brain stimulation of the subthalamic nucleus may provide a fruitful area for future research, and assist our understanding of the neural networks involved in mediating depression. Several recent studies have confirmed that depression in the PD patient is a major determinant of quality of life and that this is closely related to dysfunction in other clinically important health areas. The validity for many existing scales in the screening, diagnosis, and monitoring of depression in the PD patient has not been established. The Montgomery-Asberg Depression Rating Scale and the Hamilton Rating Scale for Depression appear to have good diagnostic sensitivity and specificity when compared with DSM-IV criteria. Recommendations for the optimal drug treatment of depression in PD are difficult to give, due to an inexplicable dearth of sizeable, placebo-controlled studies. A majority of physicians would probably now opt for a selective serotonin reuptake inhibitor in the depressed PD patient. There is no good evidence that these drugs are associated with a worsening of motor features, but they should probably not be coprescribed with selegiline, because of the risk of causing a potentially serious serotonin syndrome. Several studies have suggested that depression in the PD patient is associated with a more rapid deterioration in cognitive and motor functions, perhaps as a surrogate marker for more extensive brainstem cell loss.
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PMID:Beyond the iron mask: towards better recognition and treatment of depression associated with Parkinson's disease. 1211 90

To compare the psychometric properties of the Hamilton Rating Scale for Depression (Ham-D) in patients with stroke, Alzheimer's dementia (AD), and Parkinson's disease (PD), receiver operating characteristic curves were plotted for each group. The concurrent validity of the Ham-D with the DSM-IV criteria for major depressive disorder was high in each of these groups. However, optimal performance of the Ham-D requires the application of disease-specific cutoff scores for screening, diagnostic, and dichotomization purposes. These disease-specific cutoff scores were highest in PD, lower in AD, and lowest in stroke patients.
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PMID:Disease-specific properties of the Rating Scale for Depression in patients with stroke, Alzheimer's dementia, and Parkinson's disease. 1215 58

Five patients (4 women) with Parkinson's disease (PD) and primary major psychiatric disorder (PMPD) meeting DSM-IV criteria for the diagnosis of bipolar affective disorder (BAD) were studied. Four patients had early onset PD. Four developed a severe psychiatric disorder a few years after starting dopaminergic therapy in presence of a mild motor disability and a mild cognitive impairment, with no evidence of cerebral atrophy at CT or MRI. Two patients developed a clear manic episode; the other three presented a severe depressive episode (in one case featuring a Cotard syndrome). None showed previous signs of long term L-dopa treatment syndrome (LTS), hallucinosis or other minor psychiatric disorders. The two manic episodes occurred shortly after an increase of dopaminergic therapy and in one case rapid cyclic mood fluctuations were observed. At the onset of psychiatric symptoms, all patients had an unspecific diagnosis of chronic delusional hallucinatory psychosis (CDHP).
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PMID:Bipolar affective disorder and Parkinson's disease: a rare, insidious and often unrecognized association. 1254 47


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