Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some athletes who undertake strenuous training programs for a prolonged period of time develop the overtraining syndrome. The pathophysiology of the condition is unknown. Hypothalamic-pituitary function was studied by determining the hormonal responses to insulin-induced hypoglycemia in five asymptomatic male marathon runners during a 4-month period in which they ran 42-, 56-, and 92-km races and in four overtrained male athletes. The response of the asymptomatic runners was not different when tested 1 month before and within 48 h after the 42- and 92-km races. All four overtrained athletes presented with impaired training and racing times, apathy, and a heavy-legged feeling and were tested when overtrained and again after 4 weeks of rest. The plasma cortisol, ACTH, GH, and PRL responses to insulin-induced hypoglycemia in the four overtrained athletes were lower than their responses after the rest and lower than the responses of the asymptomatic runners. In both groups, the LH, TSH, and PRL responses to LHRH and TRH were normal. The impaired hormonal responses to insulin-induced hypoglycemia, with recovery after 4 weeks of rest, indicate hypothalamic dysfunction and may be a diagnostic marker of the overtraining syndrome.
 ...
PMID:Hypothalamic dysfunction in overtrained athletes. 298 8

Study of ACTH responsiveness to oral metyrapone and insulin hypoglycemia in children with repetitive nervous system manifestations (convulsions, coma, mental confusion apathy, tremor) has led to diagnosis of isolated ACTH deficiency in nine children within a three year period. Hypoglycemia was ascertained in five children; in four cases no hypoglycemia was proved, possibly because of promptly disappearance or because of other mechanisms accounting for clinical symptoms (occurrence of intracellular overhydratation associated with corticol deficiency is considered). The incidence of isolated ACTH deficiency in children is possibly undervalued. Reappraisal of isolated ACTH deficiency in childhood as to be considered in idiopathic spontaneous hypoglycemia and perhaps in some paroxysmal neurologic and/or digestive manifestations without proved hypoglycemia and so far poorly defined or held for epileptic fits. In order to disclose further additional tropic hormone deficiencies, and to differentiate permanent from transient impairment of ACTH responsiveness which often seems to be related to emotional deprivation syndrome, more protracted follow up studies are needed.
 ...
PMID:[Lack of ACTH responsiveness in children and paroxysmal central nervous system manifestations. (Study of nine cases of isolated ACTH deficiency) (author's transl)]. 625 61

We sought to assess whether epilepsy is associated with a higher risk of emotional reactions to frustrating stimuli, aggressive behavior, apathy, and depression, and whether these psychiatric patterns are specific to the epileptic condition. The study population consisted of referral patients 17 years and older with idiopathic or cryptogenic epilepsy (i.e., epilepsy not caused by a detectable brain lesion) without significant cognitive dysfunction. A first control was selected for each patient among patients with insulin-dependent diabetes and a second among normal blood donors. Aggressiveness in response to stressful stimuli was assessed with the Picture Frustration Study (PFS). Depression was tested by the Beck Depression Inventory. The Aggressive Behavior Scale (assessing irritability and rumination) and the Apathy Scale were also used. Odds Ratios (ORs) with 95% Confidence Intervals (95% CI) were used as the risk measure. Statistical analysis included between-group comparisons. In patients with epilepsy, the test scores were correlated to the main demographic (age, sex, education, marital status, and occupation) and clinical features (seizure types, disease duration, seizure control, and treatments). The sample included 55 patients with epilepsy, 56 diabetics, and 59 normal individuals. Patients with epilepsy and the two control groups had similar PFS scores and similar aggressiveness. Scores were also similar for the Aggressive Behavior and Apathy Scales, with similar numbers of individuals with aggressive conduct and excess rumination. Patients with epilepsy had higher depression scores. Moderate to severe depression was present in 9 cases (diabetes, 2; blood donors, 1) (P=0.004). Relative to blood donors, the OR for moderate to severe depression (95% CI) was 2.1 (0.1-61.7) for diabetes and 11.3 (1.4-247.8) for epilepsy. No significant correlation was detectable between test scores and patient and disease characteristics.
 ...
PMID:Emotional and affective disturbances in patients with epilepsy. 1266 6

Ignorance, apathy, desire to get free advice, investigation and treatment is prevalent in diabetics. Most diabetics (69.63%) are uncontrolled whether on diet, single oral drug or combination of oral drugs or insulin. Ischemic heart disease was commonest complication. Neuritis was present in the one fourth of the followed up cases and was more prevalent in uncontrolled cases. Hypertension increases with the duration of diabetes and was twice more prevalent after duration of more than 5 years. Eye changes were present in about 50% of the people examined. Abnormality increases with the duration of diabetes.
 ...
PMID:Follow up of 318 cases of diabetes mellitus. 1451 Mar 44

Brain-pancreas relative protein (BPRP) is a novel protein whose biological function remains unknown. Here, we report a possible role of BPRP in male rats exposed to chronic unpredictable mild stress (CUMS) to induce depression for 3 weeks. Compared to unstressed rats, those exposed to CUMS showed significantly less weight gain with age, decreased consumption of (and preference for) sucrose without a change in total fluid consumption. Exposure to CUMS significantly reduced open-field exploration, rearing and grooming indicative of lethargy, apathy and bodily neglect, respectively. Brain MAO-A and MAO-B activity were both significantly increased in the stressed rats. These results verified induction of depressive symptoms by CUMS. The stressed animals showed a significant reduction in pancreatic BPRP, which was accompanied by an increase in levels of blood sugar and a decrease of insulin. But they showed no apparent alteration in levels or distribution of BPRP in the hippocampal formation, which nevertheless displayed a thinner dentate granule cell layer perhaps related to elevated MAO-B activity. These findings suggest that stress-induced reduction of pancreatic BPRP may cause diabetic symptoms. Whether those symptoms in turn contribute to the onset of depression requires further study.
 ...
PMID:Effect of chronic unpredictable mild stress on brain-pancreas relative protein in rat brain and pancreas. 1615 11

To the ill patient with diabetes, the behavioral symptoms of sickness such as fatigue and apathy are debilitating and can prevent recuperation. Here we report that peripherally administered insulin-like growth factor 1 (IGF-1) attenuates LPS-dependent depression of social exploration (sickness) in nondiabetic (db/+) but not in diabetic (db/db) mice. We show that the insulin/IGF-1 mimetic vanadyl sulfate (VS) is effective at augmenting recovery from sickness in both db/+ and db/db mice. Specifically, peak illness was reached at 2 h for both VS and control animals injected with LPS, and VS mice recovered 50% faster than non-VS-treated animals. Examination of the mechanism of VS action in db/+ mice showed that VS paradoxically augmented peritoneal macrophage responsivity to LPS, increasing both peritoneal and ex vivo macrophage production of IL-1beta and IL-6 but not TNF-alpha. The effects of VS in promoting recovery from sickness were not restricted to LPS, because they were also observed after direct administration of IL-1beta. To explore the possibility that VS impairs immune-to-brain communication via vagal afferents, the vagally mediated satiety-inducing effects of cholecystokinin 8 were tested in db/+ mice. Cholecystokinin decreased food intake in saline-injected mice but not in VS-treated mice. VS also inhibited LPS-dependent up-regulation of IL-1beta and IL-6 mRNA in the brain, while increasing by 50% the cerebral expression of transcripts of the specific antagonist of IL-1 receptors IL-1RA and IL-1R2. Taken together, these data indicate that VS improves recovery from LPS-induced sickness by blocking vagally mediated immune-to-brain signaling and by up-regulating brain expression of IL-1beta antagonists.
 ...
PMID:Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness. 1621 19

During the past 50 years, the prevalence of a cluster of chronic, inactivity-related diseases including obesity, insulin resistance and type 2 diabetes mellitus (T2DM), collectively referred to as 'metabolic syndrome' (MetS) has reached global epidemic proportions. Appropriate exercise training is a clinically proven, cost-effective, primary intervention that delays and in many cases prevents the health burdens associated with MetS. Indeed, there is no single intervention with greater efficacy than physical exercise to reduce the risk of virtually all chronic diseases simultaneously. However compliance to National guidelines for physical activity remains low, with "a lack of time" the most frequently cited barrier to exercise participation by adults, irrespective of age, sex and ethnic background. Part of the growing apathy to modify lifestyle habits is that current public health recommendations may be unrealistic and unattainable for the majority of the populace. Hence, there is an urgent need for innovations in exercise prescription that can be incorporated into daily living and induce clinically beneficial health outcomes. Here we focus attention on a novel form of exercise prescription, high-intensity interval training (HIT), and provide evidence that HIT is a time-efficient and well-tolerated therapeutic intervention to improve cardio-metabolic health in a number of pre-clinical and clinical populations.
 ...
PMID:Exercise and type 2 diabetes: new prescription for an old problem. 2274 60

Magnesium is one of the most important elements in the human body and is involved in a number of biochemical processes crucial for the proper functioning of the cardiovascular, alimentary, endocrine, and osteoarticular systems. It also plays a vital modulatory role in brain biochemistry, influencing several neurotransmission pathways associated with the development of depression. Personality changes, including apathy, depression, agitation, confusion, anxiety, and delirium are observed when there is a deficiency of this element. Rodents receiving a diet deficient in magnesium displayed depressive behaviour that was reversed by antidepressant drugs. Poor nutrition, gastrointestinal and renal diseases, insulin resistance and/or type 2 diabetes, alcoholism, stress, and certain medications may lead to magnesium deficiency. Since the extracellular concentration of magnesium ions may not reflect their intracellular level, none of the current methods of evaluating magnesium status is regarded as satisfactory. The mood-improving potential of magnesium compounds have been confirmed by the results of numerous pre-clinical and clinical studies. It seems that magnesium supplementation is well-tolerated and enhances the efficacy of conventional antidepressant treatments, and as such could be a valuable addition to the standard treatments for depression, although differences in bioavailability between inorganic and organic compounds should be taken into consideration.
 ...
PMID:Magnesium and depression. 2791 Aug 8

Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor (daf-2) and syntaxin (unc-64) genes in Caenorhabditis elegans, brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults. The animals remain responsive to external stimuli; however, they fail to forage and will remain in place for >12 days or until they die. Their immobility can be prevented with drugs used to treat depression and schizophrenia and that reduce immobility in the forced swimming test. This includes amitriptyline, amoxapine, clozapine, and olanzapine, but not benzodiazepines and haloperidol. Recovery experiments confirm that immobility is induced and maintained by excessive signaling via serotonergic and muscarinic cholinergic pathways. The immobility response described here represents a potential protophenotype for avolition/anhedonia in man. This work may provide clues about why there is a significant increase in depression in patients with diabetes and suggest new therapeutic pathways for disorders featuring diminished motivation as a prominent symptom.
 ...
PMID:Insulin Signaling Deficiency Produces Immobility in Caenorhabditis elegans That Models Diminished Motivation States in Man and Responds to Antidepressants. 2923 Mar 98