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

We describe 2 new patients from a family in which 10 persons in 3 successive generations had a dominant neuropsychiatric disorder characterized by apathy, central hypoventilation, and parkinsonism. Neuropathologically, both patients showed severe neuronal loss and reactive gliosis in the substantia nigra. Neurochemical studies showed a marked depletion of dopamine in substantia nigra, putamen, and caudate nucleus, as well as reduction in serotonin content in the substantia nigra. Glutamate contents were low in frontal cortex and thalamus, and gamma-aminobutyric acid (GABA) contents were low in thalamus and substantia nigra of both patients. In addition, phosphoethanolamine contents were reduced in all brain regions of both patients, especially in the substantia nigra. One patient with severe symptoms had low levels of homovanillic acid, 5-hydroxyindoleacetic acid, and GABA in his CSF repeatedly for 3 years before death (aged 58), while the 2nd patient died (aged 51) of an unrelated cause before developing any symptoms of the familial disorder. Because brain deficiencies of multiple neurotransmitters appear to be involved, this disorder is unlikely to respond to treatment; however, neurochemical studies of CSF may make presymptomatic diagnosis feasible.
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PMID:Dominantly inherited apathy, central hypoventilation, and Parkinson's syndrome: clinical, biochemical, and neuropathologic studies of 2 new cases. 224 38

Antiepileptic drugs (AEDs) have various mechanisms of actions and therefore have diverse anticonvulsant, psychiatric, and adverse effect profiles. Two global categories of AEDs are identified on the basis of their predominant psychotropic profiles. One group has "sedating" effects in association with fatigue, cognitive slowing, and weight gain, as well as possible anxiolytic and antimanic effects. These actions may be related to a predominance of potentiation of gamma-aminobutyric acid (GABA) inhibitory neurotransmission induced by drugs such as barbiturates, benzodiazepines, valproate, gabapentin, tiagabine, and vigabatrin. The other group is associated with predominant attenuation of glutamate excitatory neurotransmission and has "activating" effects, with activation, weight loss, and possibly anxiogenic and antidepressant effects. This group includes agents such as felbamate and lamotrigine. Agents such as topiramate, with both GABAergic and antiglutamatergic actions, may have "mixed" profiles. Mechanisms of actions, activity in animal models of anxiety and depression, and clinical psychotropic effects of AEDs in psychiatric and epilepsy patients are reviewed in relationship to this proposed categorization. These considerations suggest the testable hypothesis that better psychiatric outcomes in seizure disorder patients could be achieved by treating patients with baseline "activated" profiles (insomnia, agitation, anxiety, racing thoughts, weight loss) with "sedating" predominantly GABAergic drugs, and conversely those with baseline "sedated" or anergic profiles (hypersomnia, fatigue, apathy, depression, sluggish cognition, weight gain) with "activating" predominantly antiglutamatergic agents. Systematic clinical investigation of more precise relationships of discrete mechanisms of actions to psychotropic profiles of AEDs is needed to assess the utility of this general proposition and define exceptions to this broad principle.
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PMID:Positive and negative psychiatric effects of antiepileptic drugs in patients with seizure disorders. 1049 35