Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prodromal personality features possibly presaging PD include excessive introversion, punctuality, and inflexibility. Neurobehavioral symptoms of PD that might complicate recognition and treatment of depression include loss of initiative, social withdrawal, excessive dependency indecisiveness, fatigue, apprehension about new challenges, and agoraphobia. In connection with this last feature, PD patients should be encouraged to venture out of the house because the extrapyramidal motor system, which is compromised in PD, takes over in a relaxed, familiar setting. Thus, Parkinson patients tend to have more symptoms at home than away from home. The deteriorating cognitive function which may occur in some PD patients may exacerbate social withdrawal and certain fears. Features of major depression in parkinsonian depression parallel those of the uncomplicated variety, but loss of appetite/weight and sleep disturbances may be more severe in parkinsonian depression. Serotonin depletion probably underlies the pathophysiology of this condition, in that cerebrospinal-fluid levels of serotonin's terminal metabolite decline to a greater extent in parkinsonian depression than in uncomplicated PD. After establishing the severity of depression, the clinician can contemplate several management approaches: in addition to group psychotherapy, antidepressants (after discontinuation of selegiline to avoid adverse events), particularly tricyclic antidepressants with low anticholinergic action (i.e., low potential for confusion) or selective serotonin reuptake inhibitors may be administered. Depressive symptoms during "off" periods (i.e., at nadirs of drug levels) may be relatively intractable and warrant patient and family education. Finally, electroconvulsive and light therapy represent appropriate therapeutic modalities for selected patients.
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PMID:Depression: impact and management by the patient and family. 1022 3

There is some evidence that the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) may be involved in the pathogenesis of seasonal affective disorder (SAD). Short-term tryptophan (TRP) depletion was carried out in 18 drug-free remitted patients who met DSM-IV criteria for SAD. Behavioral effects were measured with the Hamilton Depression Rating Scale (HDRS) both 24 h before and 24 h after TRP depletion. Some of the patients showed behavioral responses such as lowered mood, feelings of guilt, loss of interest, agitation, loss of energy, fatigue, social withdrawal, increased appetite, and carbohydrate craving. It was the aim of our study to investigate whether the genotypes of the serotonin transporter gene were associated with symptoms of transient depressive relapse after TRP depletion. In addition, we matched the SAD patients with healthy control subjects to see if alleles and genotypes of the serotonin transporter gene were associated with SAD. High molecular weight DNA was isolated from peripheral blood leukocytes using standard methods. For the 5-HTT receptor gene, a 17-bp repetitive element of intron 2 was genotyped (variable number tandem repeat, VNTR). Alterations in HDRS scores after TRP depletion showed no significant association with alleles or genotypes of the 5-HTT gene, although heterozygotes showed a trend toward increased HDRS scores. The serotonin transporter is known to play a critical role in the termination of serotonergic neurotransmission by sodium-dependent uptake of 5-HT into the presynaptic neuron. The present study in a small group of SAD patients was unable to demonstrate that the 5-HTT gene plays a role in the pathogenesis of SAD or in short-term depressive relapse after TRP depletion.
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PMID:Behavioral effects of tryptophan depletion in seasonal affective disorder associated with the serotonin transporter gene? 1033 77

Rizatriptan (MAXALT(TM), Merck & Co., Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action for the acute treatment of migraine. This randomized, double-masked, double-dummy, placebo-controlled study compared rizatriptan 10 mg to naratriptan (NARAMIG(TM), AMERGE(TM), both Glaxo Wellcome plc) 2.5 mg in 522 patients treating a single migraine attack. Rizatriptan was more effective than naratriptan. Rizatriptan provided earlier headache relief than naratriptan (hazard ratio 1.62, p < 0.001), acting as early as 30 min. More patients were pain free at 2 h on rizatriptan than on naratriptan (44.8 vs. 20.7%, p < 0.001). Rizatriptan also provided earlier relief of associated migraine symptoms within 2 h than naratriptan and more patients had normal function at 2 h (39.3 vs. 22.6%, p < 0. 001). Both active treatments were effective compared to placebo. Both active treatments were well tolerated. The most common side effects with rizatriptan were dizziness, asthenia/fatigue, nausea and somnolence, while the most common side effects with naratriptan were dizziness and asthenia/fatigue.
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PMID:Comparison of rizatriptan 10 mg vs. naratriptan 2.5 mg in migraine. 1052 45

5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the perception of exercise-induced fatigue. Sumatriptan is a selective 5-HT(1B/D) receptor agonist which does not cross the blood-brain barrier. The aim of the present study was to determine the effect of sumatriptan on exercise capacity. Ten healthy male subjects (mean age 28.4+/-10.8 years) performed a maximal treadmill exercise test according to the Bruce protocol with expired gas analysis on two occasions. Either 6 mg of sumatriptan or placebo was administered subcutaneously in a randomized, double-blind, placebo-controlled, cross-over design. Exercise time was greater after placebo compared with sumatriptan [914 and 879 s respectively; 95% confidence interval (CI) of difference 12.1 s, 59.1 s; P = 0.008]. There was no significant effect on peak oxygen consumption (placebo, 50.6+/-6.3 ml.min(-1).kg(-1); sumatriptan, 51.7+/-7.6 ml.min(-1).kg(-1)). Sumatriptan administration resulted in decreases in both heart rate (sumatriptan, 188+/-14 beats/min, placebo, 196+/-12 beats/min; 95% CI of difference 12.6, 2.6; P = 0.008) and respiratory exchange ratio (sumatriptan, 1.23+/-0.06; placebo, 1.26+/-0.07; 95% CI of difference 0.05, 0.01; P = 0.01) at peak exercise. There were no significant differences in blood pressure, heart rate or submaximal oxygen consumption between sumatriptan and placebo treatments at any stage of exercise. Thus sumatriptan reduces maximal exercise capacity in normal males. The failure to demonstrate any haemodynamic or cardiorespiratory effect suggests that sumatriptan enhances perception of fatigue by a peripheral mechanism affecting 5-HT modulation.
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PMID:Sumatriptan reduces exercise capacity in healthy males: a peripheral effect of 5-hydroxytryptamine agonism? 1081

The fluorescent dye sulforhodamine-101 undergoes synaptic activity-dependent endocytotic uptake and consequent retrograde transport in presynaptic neurons. We used sulforhodamine to identify thoracolumbar spinal premotor neurons (T11-L6) activated during serotonin (5-HT) -induced hindlimb locomotor-like activity in the in vitro neonatal rat spinal cord preparation. Sulforhodamine labeling required locomotor-like activity because few neurons were labeled unless bath applied 5-HT recruited the locomotor rhythm. In contrast, N-methyl-D-aspartate (NMDA; 5 microM) profoundly increased spinal neuronal labeling irrespective of locomotor activity. The contribution of false-positive activity labeling during locomotion induced by application of NMDA with 5-HT (Kjaerulff et al. [1994] J Physiol (Lond). 478:265-273) necessitated the present re-mapping of sulforhodamine-labeled neurons. During 5-HT-evoked locomotion, the sulforhodamine-labeled neurons were diffusely scattered within the spinal cord with predominant labeling in lamina VII. Motor nuclei (lamina IX) and superficial laminae (I-II) were typically devoid of labeled cells in the isolated spinal cord. However, unilateral labeling of motoneurons was achieved when the ipsilateral hindlimb remained attached, suggesting that uptake in motoneurons requires an intact neuromuscular junction. The rostrocaudal incidence and distribution of labeled neurons was uniform in spinal segments L1-L5, with reduced numbers observed in thoracic and L6 spinal segments. Mean total cell labeling was less than 400 per spinal segment, suggesting recruitment from a very small fraction of the neurons contained within the spinal cord (calculated at < 0.1%). These results are consistent with the limited transfer of locomotor-related synaptic activity (Raastad et al. [1996] Neuron 17:729-738) and severe synaptic fatigue (Lev-Tov and Pinco [1992] J Physiol. 447:149-169; Pinco and Lev-Tov [1993] J Neurophysiol. 70:1151-1158; Fleoter and Lev-Tov [1993] J Neurophysiol. 70:2241-2250) observed in the neonatal rat spinal cord.
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PMID:Diffuse distribution of sulforhodamine-labeled neurons during serotonin-evoked locomotion in the neonatal rat thoracolumbar spinal cord. 1088 Sep 90

Implications of exercise on serotonergic neuromodulation in the brain have been investigated in two studies. Acute paroxetine (selective serotonin (5-HT) reuptake inhibitor) administration to endurance athletes, who performed a cycle ergometer test to exhaustion at moderate intensity, reduced time to exhaustion and post exercise cognitive performance in comparison to trials with placebo or BCAA administration. Furthermore, during a 3-week moderate endurance training of sedentary males basaline values of Bmax of 5-HT transporters (5-HTT) and 5-HT2A receptors (5-HT(2A)R) on isolated platelet membranes increased while plasma prolactin (PRL) concentrations decreased as well as mood and physical efficiency improved. In contrast, after an excessive training program over four weeks, well-trained endurance athletes showed no change of Bmax of 5-HTT, but a decline of 5-HT(2A)R density and an increase in basal plasma PRL concentration. Mood was impaired and central fatigue increased. Thus, the impact of exercise on 5-HT neurotransmission may depend on training state of athletes and extent of exertion. The theoretical background of the implication of exercise and the effect of long lasting exhaustive exercise in athletes on mental and physical efficiency or central fatigue are evaluated. The significance of the primary disturbance of central neuromodulation and dysfunction of 5-HTT, 5-HT receptor subtypes and the phosphoinositol signal transduction as well as the limited modulation capacity of the 5-HT system in overstrain are also addressed.
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PMID:Influence of exercise on serotonergic neuromodulation in the brain. 1131 Sep 29

Depression is a most common psychiatric complication of Parkinson's patients. Approximately 30% of Parkinson's patients show depressive mood changes. Loss of interest, feelings of hopelessness, marked loss of energy and psychomotor retardation are common depressive symptoms with parkinsonism. Suicidal ideations and delusions are less frequent in Parkinson's patients with depression in compared to endogenous depression. Somatic symptoms, like fatigue, constipation, headache, insomnia, loss of appetite, dizzinees and sweating are usually seen in Parkinson's patient with depression. Serotonin reuptake inhibitors and selegiline are recommended for the treatment of depression in parkinsonian patients.
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PMID:[Parkinson's disease]. 1151 61

As shown in the first part of this review, well equilibrated neurotransmission in which 5-HT plays a dominant role is important for proper neuromodulation and adjustment of neuronal network elements. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after different forms of exertions, thereby preventing transient dysregulation. Impairment of neuromodulation and neuronal network in the brain with transient dysfunctions or permanent substantial deficits at manifestation of various types of depression results from prevalent impairment of 5-HT neurotransmission and its central interaction with other neurotransmitter systems. Exercise-induced increase of free tryptophan (TRP) in blood occurs due to liberation from albumin, which is caused by adrenergically induced lipolysis of free fatty acids and results in higher free TRP uptake into the brain. Consecutively enhanced serotonin (5-HT) biosynthesis does not per se initiate mood impairment or central fatigue. It is suggested that in overtrained athletes central fatigue, mental deficiency and behavioral alterations with depressive mood are probably not primarily caused by metabolic and neuromuscular alterations. The primary trigger of these transient behavioural alterations might instead be initiated by a central exhaustive exercise stress which elicits impairment of complex neuromodulation, also afflicting the interaction of central neurotransmitters or hypothalamic neuropeptides and releasing factors. In a consecutive correction of the variation, the implication of the serotonergic system on the central neuromodular disturbance might improve or prevent the progressive course both in transient and in permanent mental disorders. However, an unsuccessful attempt to improve the depressive symptomatology leads mostly to an overproportional exaggeration of the behavioral changes.
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PMID:Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part II. 1159 Apr 75

The aim of this study was to assess extracellular glucose changes in hippocampus in response to physical exercise and to determine the influence of glucose supplementation. In the same time, we have observed the changes in serotonin, in order to study the relationship between glucose and serotonin during exercise. Both glucose and serotonin were assessed using microdialysis. Exercise induced an increase in extracellular glucose levels over baseline during exercise to 121.1 +/- 3.0% (P < 0.001), then a decrease to baseline during recovery. The serotonin followed glucose changes during the first 90 min of exercise, but followed a different pattern during recovery, increasing to a maximum of 129.9 +/- 7.0% after 30 min of recovery (P < 0.001). When a 15% glucose solution was infused (10 microL x min(-1)) during exercise and recovery, blood glucose concentration was increased, but extracellular brain glucose decreased to reach a minimum of 73.3 +/- 4.6% after 90 min of recovery (P < 0.001). Serotonin was always the mirror-reflect of cerebral glucose, with a maximum increase of 142.0 +/- 6.9% after 90 min of recovery (P < 0.001). These results show that exercise induces changes in brain glucose and 5-hydroxytryptamine (5-HT) levels, which were dramatically modified by glucose infusion. Taking into account the implication of brain 5-HT in central fatigue, they suggest that if glucose supplementation, before and during exercise, undoubtedly increase performance because of its peripheral positive action, it would have a negative impact on the quality of recovery after the end of the exercise.
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PMID:Exercise-induced changes in brain glucose and serotonin revealed by microdialysis in rat hippocampus: effect of glucose supplementation. 1168 80

An increase in the concentration of serotonin in the brain has been shown to cause fatigue during exercise in humans and experimental animals. This type of fatigue is referred to as central fatigue and is likely to be mediated by the concentration of serotonin as well as serotonin receptor sensitivity. Serotonin (5-HT) receptor antagonism in humans and experimental animals has been shown to improve endurance performance. A previous report has shown decreased receptor sensitivity in athletes compared to sedentary controls. It is unclear whether this is due to a training adaptation or if individuals are predisposed to enhanced athletic performance due to their inherent decreased receptor sensitivity. The present study investigated changes in 5-HT receptor sensitivity in response to aerobic exercise. Subjects completed 3 x 30 min of stationary cycling at 70 % of their peak aerobic power (.V(O(2)peak)) for 9 weeks. Serotonin receptor sensitivity was assessed indirectly by measuring the neuroendocrine response following administration of a serotonin agonist (buspirone hydrochloride). The neuroendocrine response following administration of a placebo was also investigated in a blind crossover design. A group of sedentary control subjects was also recruited to control for seasonal variations in central receptor sensitivity. The training caused a significant increase in .V(O(2)peak)) (3.1 +/- 0.16 to 3.6 +/- 0.15 l min(-1), P < 0.05) and endurance capacity (93 +/- 8 to 168 +/- 11 min, P < 0.05), but there was no change (P > 0.05) in the neuroendocrine response in the presence of a serotonin agonist. However, one-quarter of the subjects in the training group demonstrated decreases in receptor sensitivity. These results suggest that despite increases in .V(O(2)peak)) and endurance performance, there was no measurable change in 5-HT receptor sensitivity in the presence of a serotonin agonist. In addition, it is possible that changes in receptor sensitivity may take longer to occur, that the training stimulus used in the present investigation was inadequate and/or that changes occurred in receptor subtypes that were not probed by the agonist used in the present investigation.
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PMID:Short term aerobic exercise training in young males does not alter sensitivity to a central serotonin agonist. 1180 62


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