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)

Whereas the instability of positive symptoms over time is well recognized, the instability of negative symptoms is still debated. This controversy could be due to the fact that different negative symptoms have been studied in different phases of schizophrenia. We, therefore, hypothesized that some negative symptoms would improve whereas others would remain perfectly stable during the remission of the acute phase of illness. We further hypothesized that the changes in these negative symptoms would be linked to changes in other domains such as extrapyramidal, depressive and positive symptomatology. A broadly defined sample of schizophrenic patients was evaluated at admission and discharge of the hospital with the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), the Montgomery and Asberg Depression Rating Scale (MADRS) and the Extrapyramidal Symptoms Rating Scale (ESRS). Doses of antipsychotic medications were converted into chlorpromazine-equivalents. Fifty-seven patients (mean age 40.3 years old) were included in the sample and followed-up during their hospitalization. All the sub-scores of the SANS-SAPS decreased significantly but 4 items of the SANS belonging to the affective flattening subscale (unchanging facial expression, decreased spontaneous movements, paucity of expressive gestures and lack of vocal inflections) and one item belonging to the alogia subscale (poverty of speech) did not vary significantly, showing the necessity of taking into account the individual items of the SANS rather than the subscale scores to evaluate the course of negative symptoms. Changes in all the SANS subscores except the alogia subscore were associated with variations in scores of other scales. The change in attentional subscores was positively correlated to the change in the positive formal thought disorder subscores, probably because both belong to the same syndrome. The change in affective flattening subscores was associated with changes in depressive and akinetic scores and 28% of the variance of the change in the affective flattening subscores was explained by the change in the MADRS scores. Changes in avolition-apathy and anhedonia subscores were also associated with changes in MADRS scores but not with the change in akinesia scores.
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PMID:Negative symptoms in schizophrenia: their evolution during an acute phase. 856 93

While many acutely ill schizophrenic patients suffer from depressive symptoms, most studies on the efficacy of antipsychotic drugs focus on positive and negative symptoms. Dimensional models of schizophrenic symptoms, based on confirmatory factor analysis (CFA) using structural equation modelling, offer a methodological alternative to compare antipsychotics on empirically justified latent factors. The present report is a refined analysis of a published double-blind study on the D2/D3-selective antagonist amisulpride (ASP) versus the mixed D1-5/5-HT2 antagonist flupentixol (FPX). CFA was applied to Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Bech-Rafaelsen Melancholia Scale and Simpson-Angus Scale subscores to examine differential effects of high doses of ASP and FPX on negative and depressive symptom dimensions in 126 acutely ill schizophrenic patients. A four-factor model comprising the full spectrum of acute symptomatology and a three-factor model ('negative', 'anhedonia-apathy', 'depressive') restricted to negative and depressive symptoms were yielded with an identical 'depressive' dimension in both models. Analyses of CFA-derived factor scores showed that ASP was significantly superior to FPX regarding the latent 'depressive' dimension, independent of baseline scores, dosage and changes in akinesia. Neither the negative' dimension nor 'anhedonia-apathy' showed significantly different treatment effects. CFA-based analyses appear to be suitable for psychotropic drug evaluation when more refined and data-related information on drug efficacy profiles are required.
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PMID:Differential effects of high-dose amisulpride versus flupentixol on latent dimensions of depressive and negative symptomatology in acute schizophrenia: an evaluation using confirmatory factor analysis. 1217 87

Comparative investigation of motor and neuropsychological functions was conducted in 17 patients with clinically established diagnosis of dementia with Lewy bodies (DLB), 21 patients with Parkinson's disease (PD) without dementia and 26 patients with dementia (PDD). No significant differences were found in overall severity of parkinsonian features. However, comparing to PD, patients with DLB rarely had resting tremor, bilateral parkinsonism onset and good response to levadopa medication but more frequently exhibited gaze up palsy and myoclonus. Patients with PDD had more prominent akinesia, rigidity and axial disturbances, as compared to the PD patients without dementia, but there were no significant differences in these variables between patients with DLB and PDD. Comparing to PDD patients, those with DLB poorly performed on the tests measuring attention, verbal fluency and visual-spatial functions. Behavioral disturbances (especially apathy, aspontaneity, euphoria, obsessive-compulsive syndrome, dysinhibition, environment dependence) were severer in the patients with DLB and PDD, but no significant differences were found between these two groups. All the patients with DLB, 14 patients with PDD (53.8%) and 2 patients without dementia (7.4%) had psychotic disorders, which emerged later and were less pronounced in the patients with DLB compared to PDD patients. However, no significant differences were found in motor and neuropsychological impairment between DLB and PDD with psychotic disorders. The results may indicate a typological similarity of clinical manifestations of DLB and PDD that suggest nosologic proximity of these conditions included to synucleinopathies group.
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PMID:[Comparative study of Parkinson's disease and dementia with Lewy bodies]. 1487 Jun 86

The clinical signs grouped under the concept of apathy are a common feature of prefrontal and basal ganglia lesions or dysfunctions and can therefore help to improve our understanding of the functional anatomy of the prefrontal-basal ganglia system. Apathy is here defined as a quantitative reduction of voluntary, goal-directed behaviors. The underlying mechanisms responsible for apathy can be divided into three subtypes of disrupted processing: 'emotional-affective', 'cognitive' and 'auto-activation'. Apathy due to the disruption of 'emotional-affective' processing refers to the inability to establish the necessary linkage between emotional-affective signals and the ongoing or forthcoming behavior. It may be related to lesions of the orbital-medial prefrontal cortex or to the related subregions (limbic territory) within the basal ganglia (e.g. ventral striatum, ventral pallidum). Apathy due to the disruption of 'cognitive' processing refers to difficulties in elaborating the plan of actions necessary for the ongoing or forthcoming behavior. It may be related to lesions of the dorsolateral prefrontal cortex and the related subregions (associative territory) within the basal ganglia (e.g. dorsal caudate nucleus). The disruption of 'auto-activation' processing refers to the inability to self-activate thoughts or self-initiate actions contrasting with a relatively spared ability to generate externally driven behavior. It is responsible for the most severe form of apathy and in most cases the lesions affect bilaterally the associative and limbic territories of the internal portion of the globus pallidus. It characterizes the syndrome of 'auto-activation deficit' (also known as 'psychic akinesia' or 'athymormia'). This syndrome implies that direct lesions of the basal ganglia output result in a loss of amplification of the relevant signal, consequently leading to a diminished extraction of this signal within the frontal cortex. Likewise, apathy occurring in Parkinson's disease could be interpreted as secondary to the loss of spatial and temporal focalization of the signals transferred to the frontal cortex. In both situations (direct basal ganglia lesions and nigro-striatal dopaminergic loss), the capacity of the frontal cortex to select, initiate, maintain and shift programs of actions is impaired.
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PMID:Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. 1620 33

The course of negative and positive symptoms was studied in neuroleptic-treated patients over a 3-year period, in consideration also of the initial phase of illness (post-acute or chronic). This study was carried out in a broadly defined schizophrenic sample, in order not to give preference to one diagnostic subgroup over another. Forty-six patients were evaluated every year for 3 years, 23 in the post-acute group and 23 in the chronic group. Aggravations of the Clinical Global Impression (CGI) and of the SANS total score were observed, regardless of the group (chronic or post-acute). This global aggravation confirmed Kraepelin's concept of dementia praecox; moreover, this aggravation was not due to an increase in the number of patients relapsing, or to an aggravation of akinesia. Three types of negative and positive symptom courses were observed: i) the mean sub-scores of positive symptoms, such as hallucinations, delusions, positive formal thought disorders, and of negative symptoms such as flattening affect, avolition/apathy and attentional impairment, did not vary significantly over time in either group; ii) the mean sub-scores of bizarre behavior and alogia fluctuated over time (p < 0.05) and only poverty of speech was perfectly stable among the items constituting alogia; iii) the mean subscores of anhedonia/asociality worsened significantly over time irrespective of the groups (p < 0.05), and among the items constituting anhedonia, recreational interest-activities and intimacy-closeness abilities worsened (p < 0.05 and p < 0.01, respectively). This aggravation was neither due to an increase in neuroleptic doses nor to the duration and chronicity of illness. However, negative symptoms, except anhedonia, can be reversible in some patients. The very strong stability of anhedonia, whatever the group, emphasize the importance of taking anhedonia into account in future diagnostic classifications.
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PMID:Stability of positive and negative symptoms in schizophrenic patients: a 3-year follow-up study. 1969 45

A dopaminergic deficiency in patients with Parkinson's disease (PD) causes abnormalities of movement, behaviour, learning, and emotions. The main motor features (ie, tremor, rigidity, and akinesia) are associated with a deficiency of dopamine in the posterior putamen and the motor circuit. Hypokinesia and bradykinesia might have a dual anatomo-functional basis: hypokinesia mediated by brainstem mechanisms and bradykinesia by cortical mechanisms. The classic pathophysiological model for PD (ie, hyperactivity in the globus pallidus pars interna and substantia nigra pars reticulata) does not explain rigidity and tremor, which might be caused by changes in primary motor cortex activity. Executive functions (ie, planning and problem solving) are also impaired in early PD, but are usually not clinically noticed. These impairments are associated with dopamine deficiency in the caudate nucleus and with dysfunction of the associative and other non-motor circuits. Apathy, anxiety, and depression are the main psychiatric manifestations in untreated PD, which might be caused by ventral striatum dopaminergic deficit and depletion of serotonin and norepinephrine. In this Review we discuss the motor, cognitive, and psychiatric manifestations associated with the dopaminergic deficiency in the early phase of the parkinsonian state and the different circuits implicated, and we propose distinct mechanisms to explain the wide clinical range of PD symptoms at the time of diagnosis.
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PMID:Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms. 1990 11

Huntington's disease (HD) is caused by a CAG repeat expansion in exon 1 of the HD gene resulting in a long polyglutamine tract in the N-terminus of the protein huntingtin. Patients carrying the mutation display chorea in early stages followed by akinesia and sometimes dystonia in late stages. Other major symptoms include depression, anxiety, irritability or aggressive behavior, and apathy. Although many neuronal systems are affected, dysfunction and subsequent neurodegeneration in the basal ganglia and cortex are the most apparent pathologies. In HD, the primary hypothesis has been that there is an initial overactivity of glutamate neurotransmission that produces excitotoxicity followed by a series of complex changes that are different in the striatum and in the cortex. This review will focus on evidence for alterations in dopamine (DA)-glutamate interactions in HD, concentrating on the striatum and cortex. The most recent evidence points to decreases in DA and glutamate neurotransmission as the HD phenotype develops. However, there is some evidence for increased DA and glutamate functions that could be responsible for some of the early HD phenotype. Significant evidence indicates that glutamate and dopamine neurotransmission is affected in HD, compromising the fine balance in which DA modulates glutamate-induced excitation in the basal ganglia and cortex. Restoring the balance between glutamate and dopamine could be helpful to treat HD symptoms.
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PMID:Dopamine and glutamate in Huntington's disease: A balancing act. 2040 48

Among the recently well appreciated non-motor symptoms in Parkinson's disease (PD), depression plays a prominent role due to its frequency and impact on quality of life. However, depression may be confounded by motor symptoms, especially akinesia and other non-motor symptoms such as apathy, anxiety and dementia. Data on specific diagnostic tools or treatment for depressive symptoms in PD patients are still sparse. Here we summarize an expert opinion based on available data and clinical experience.
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PMID:Depression in Parkinson's disease. 2156 65

Parkinson disease (PD) is characterized by a number of motor and behavioral abnormalities that could be considered deficits of a "no task" or "resting" state, including resting motor findings and defects in emerging from a resting state (e.g., resting tremor, elevated resting tone, abulia, akinesia, apathy). PET imaging, and recently, the MRI technique of continuous arterial spin labeling (CASL) have shown evidence of changes in metabolic patterns in individuals with PD. The purpose of this study was to learn if the presence of PD could be "predicted" based on resting fluctuations of the BOLD signal. Participants were 15 healthy controls, 14 subjects with PD, and 1 subject who presented as a control but later developed PD. The amplitude of the low frequency fluctuation (ALFF) was used as an index of brain activity level in the resting state. Participants with PD using this index showed a reliable decrease in activity in a number of regions, including the supplementary motor cortex, the mesial prefrontal cortex, the right middle frontal gyrus, and the left cerebellum (lobule VII/VIII) as well as increased activity in the right cerebellum (lobule IV/V). Using a cross validation approach we term "Reliability Mapping of Regional Differences" (RMRD) to analyze our sample, we were able to reliably distinguish participants with PD from controls with 92% sensitivity and 87% specificity. Our "pre-diagnostic" subject segregated in our analysis with the PD group. These results suggest that resting fMRI should be considered for development as a biomarker and analytical tool for evaluation of PD.
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PMID:Reliability analysis of the resting state can sensitively and specifically identify the presence of Parkinson disease. 2192 67

Dopaminergic neurons play a major role in controlling movement and behavior. In Parkinson's disease (PD), dopaminergic denervation is responsible for a number of motor and non-motor symptoms including tremor, rigidity and akinesia and as well apathy, impulsivity and other behavioral complications frequently reported in these patients. In this review, we will summarize the possible proposed dopaminergic mechanisms responsible for these complications in PD, focusing mainly on the role of this neurotransmitter in behavioral symptoms.
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PMID:Behavioral disorders in Parkinson's disease: the role of dopamine. 2426 57


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