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)

The review begins by a brief presentation of the present state of knowledge on the multiplicity of brain dopamine receptors. The molecular basis of their distinction is reported, as well as the most specific ligands for each receptors type: D1, D2 (their isoforms A and B), D3, the putative D4 and autoreceptors. Then the review focuses on the respective location of D1 receptors (mainly linked positively to an adenylate cyclase) and of so-called D2 (lacking precision for distinguishing D2, D3 or D4), at the cellular level. The theoretical aspects of the functional interactions between these D1 and D2 receptors suggest four possibilities: Antagonism, indifference, additive synergy and potentiation. The effects resulting from the simultaneous administration of either D1 and D2 dopamine agonists or D1 and D2 dopamine antagonists were considered on various behaviours or functions. The four predicted types of interactions were found: D1/D2 antagonism on thermoregulation, D1/D2 indifference on nociception, additive synergy on the traction test, on anorexia or on the latency of the acoustic startle response, and finally potentiation on stereotypies or climbing behaviour. These data are completed by many other reported in an abundant literature about these interactions, which appear as modalities of regulation: their alterations might take part in several pathological states.
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PMID:[Brain dopamine receptors. Interactions between D1 and D2 receptors, and dopamine mediated behaviour]. 168 22

A 68 year-old man with a history of right thalamic hemorrhage demonstrated radiologically in the pulvinar and posterior portion of the dorsomedian nucleus developed a clinical picture of severe physical sequelae associated with major affective, behavioral and psychic disorders. Affective manifestations were a permanent anxiety-depression state contrasting with indifference to his surroundings. Behavioral changes included marked apathy, inertness and hypersomnia, together with occasional clastic agitated episodes and verbal and gestural stereotypies and soliloquies. Psychic sequelae were psychotic in nature: depersonalization crises, delusions of persecution, multisensorial hallucinations and absurd acts.
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PMID:[Thalamic dementia after a unilateral hemorrhagic lesion of the right pulvinar]. 382 7

Genetic screening of 171 patients with frontotemporal lobar degeneration disclosed 14 patients, across nine pedigrees, with mutations in the intron to exon 10 in the tau gene, a region regulating the splicing of exon 10 via a stem loop mechanism. Thirteen of these patients had the +16 splice site mutation and one had the +13 splice site mutation. Affected members of all nine families presented with changes in behaviour and social conduct that were prototypical of frontotemporal dementia (FTD). In all patients with the +16 splice site mutation, the behavioural profile was characterized by disinhibition, restless overactivity, a fatuous affect, puerile behaviour and verbal and motor stereotypies. The single patient with the +13 mutation presented a contrasting picture of apathy and inertia. In addition, all patients had evidence of semantic loss. Pathologically, five of the six patients so far autopsied shared frontotemporal atrophy with involvement of the substantia nigra. The underlying histology was that of microvacuolar-type cortical degeneration with a few swollen cells. Tau pathology was widespread throughout the brain and present in neurones and glial cells, mostly in the frontal and temporal cortical regions. This was in the form of neurofibrillary tangles and amorphous tau deposits (pre-tangles); Pick bodies were not observed. Ultrastructurally, the tau filaments had a twisted, ribbon-like morphology distinct from the paired helical filaments of Alzheimer's disease. One patient died from an unrelated illness whilst in the early clinical stages of FTD. In this patient, cortical microvacuolar and astrocytic changes were absent, though there were scattered neurones and glial cells, immunoreactive to tau, throughout the cortical and subcortical regions. The disease process underlying the neurodegeneration within these inherited forms of FTD may therefore stem directly from early, primary alterations in the function of tau. All eight families with the +16 mutation seem to be part of a common extended pedigree, possibly originating from a founder member residing within the North Wales region of Great Britain.
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PMID:Inherited frontotemporal dementia in nine British families associated with intronic mutations in the tau gene. 1191 8

Behavioral changes in patients with FTD can be interpreted by considering damage to the frontal lobes themselves and considering the interaction between the frontal lobes and other neural systems such as the posterior association cortices, the limbic system, and basal ganglia. Loss of insight and apathy primarily result from frontal lobes involvement. The latter is probably correlated with the severity of medial frontal-anterior cingulate involvement. Stimulus-bound behavior such as imitation behavior, utilization behavior and environmental dependency syndrome is caused by an imbalance between the activities of the frontal and parietal lobes. Frontal lobe damage, particularly damage to the medial frontal area, result in liberation of the parietal lobe activity, leaving the patient subject to any stimuli from the external environment. Disinhibition such as antisocial behavior is produced by an imbalance between the activities of the frontal and limbic lobes. Namely, loss of control of the frontal lobe, especially the orbitofrontal area, over the limbic system results in acts led by instinctive desires and uncontrolled by reason. Stereotypic behavior is due to an imbalance between the activities of the frontal cortex and basal ganglia. These behaviors range from simple stereotypies to complex repeated actions such as roaming, clock-watching or adherence to a strict daily timetable.
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PMID:[Symptomatology of fronto-temporal dementia]. 1919 45

The 9q Subtelomeric Deletion Syndrome (9qSTDS) is clinically characterized by mental retardation, childhood hypotonia, and facial dysmorphisms. Haploinsufficiency of the EHMT1 gene has been demonstrated to be responsible for its core phenotype. In a significant number of patients behavioral abnormalities like aggression, impulsivity, and chaotic behaviors are present as well as epileptic phenomena. Reports about the developmental, behavioral, and neuropsychiatric aspects of 9qSTDS are scarce and mostly limited to young patients only. In this report, the behavioral and neuropsychiatric characteristics of one male and one female middle-aged patient are described in whom the genetic diagnosis, interstitial and telomeric 9q deletion, respectively, was established recently. In both patients a remarkable sleep disturbance, characterized by frequent awakenings and daytime sleepiness, was present as well as a prominent apathy syndrome. The observed motor signs such as rigid flexure of the arms and finger stereotypies persisted over a period of many years and could therefore not be viewed as symptoms of catatonia. It is concluded that the proposed behavioral phenotype of 9qSTDS comprises at least an erratic sleep pattern and an enduring severe apathy.
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PMID:Behavioral phenotype in the 9q subtelomeric deletion syndrome: a report about two adult patients. 1964 12

The welfare of an animal is ensured if it is able to fully satisfy its essential species-typical needs in all functional aspects of behaviour. In mink, stereotypies and apathy, internal and/or external injuries as well as increased susceptibility to disease have been known to occur as a result of chronic stress. The non-invasive method of analysing faecal cortisol metabolites (FCM) allows conclusions to be drawn about the stress level in the respective housing system. The objective of this study is to find out how the cortisol metabolites content in the faecal changes with increasing age of the mink under semi-natural housing conditions. Thus, 40 American mink (Neovison vison) were housed in two outdoor enclosures imitating natural conditions. Throughout the entire study (13th to 32nd week of life), faecal samples were collected to measure cortisol metabolites. No differences in FCM concentrations between the two outdoor enclosures were found. In the young mink lower, less fluctuating FCM levels were found than in older animals. After the first faecal collection in the 13th/14th week of life, the level of metabolites decreased slightly (p = 0.032; 17th/18th week). From the 22nd/23rd week onwards until the 30th/31st week, shortly before the animals were pelted, continuously increasing concentrations were then measured. Increasing FCM levels with advancing age of the animals are probably attributable to the onset of sexual maturity and/or the respective season. This has to be taken into account in future studies using this method for assessing welfare and when comparing different mink housing systems.
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PMID:Age-dependent baseline values of faecal cortisol metabolites in the American mink (Neovison vison) under semi-natural housing conditions. 2403 8

Corticobasal syndrome (CBS) is a neurodegenerative disease characterized by progressive asymmetrical rigidity and apraxia, cortical sensory loss, myoclonus, dystonia, and cognitive impairment. CBS is usually sporadic and associated with tau pathology but there are reports of TDP-43 pathology. We screened 39 CBS cases to determine if any of the cases could be explained by a G4C2-repeat expansion in a noncoding region of C9orf72 gene, the most common genetic cause of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. One patient with CBS had a large (>50 repeats) expansion in C9orf72. Our case features a 63-year-old right-handed woman who developed mild apathy 9 years before presentation, which progressed to include behavioral symptoms, oral stereotypies, significant language impairment, parkinsonism and apraxia. A magnetic resonance imaging acquired at age 60 years, that is, 6 years after disease onset revealed significant asymmetric left > right frontotemporal atrophy, including orbitofrontal and parietal areas. Her father developed a behavioral syndrome and died at an early age. This case highlights the importance of genetic screening for C9orf72 in patients with CBS.
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PMID:Mutation analysis of C9orf72 in patients with corticobasal syndrome. 2616 5

Frontotemporal dementia is a neurodegenerative disorder of which the behavioral variant is most common. This condition is currently considered the most common cause of dementia in people younger than 60 years. Here, we present two unrelated cases in which the typical symptoms were cognitive and behavioral progressive deterioration and psychiatric disorders such as disinhibition, impulsive acts, apathy, lack of empathy, stereotypies, and changes in eating habits. The first case exhibited pathological gambling as the initial symptom and resided in a psychiatric facility for a year. Notably, this was the second such case in Latin America and one of only a few such cases reported worldwide. The second case presented with epileptic seizures during evolution. In both cases, brain magnetic resonance revealed left-predominant frontotemporal atrophy, and alterations in executive function were evident during neuropsychological assessments.
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PMID:[Pathological gambling and epilepsy in patients with frontotemporal dementia: Two case reports]. 2783 27