Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apolipoprotein E (APOE) locus on chromosome 19 has been shown to modify risk, and age at onset, of Alzheimer's disease (AD). The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus. Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28% had major depression, 17% had minor depression, 30% had delusions, and 14% had hallucinations; 69% were carriers of at least one APOE E4 allele (14% homozygous E4/E4, 49% heterozygous E3/E4, 6% heterozygous E2/E4, 29% homozygous E3/E3, 2% heterozygous E2/E3). Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes. Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology.
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PMID:Depression, delusions, and hallucinations in Alzheimer's disease: no relationship to apolipoprotein E genotype. 901 30

Apolipoprotein E (ApoE) allele frequencies were examined in a population-based sample (n = 475: age range 65-84 years: Amsterdam Study of the Elderly). The relation of ApoE epsilon 4 with dementia and with various types of late-life depression was studied. Depression was measured with the Geriatric Mental State schedule. Dementia was diagnosed by DSM-III-R criteria. It was expected that ApoE epsilon 4 allele frequencies would be elevated not only in Alzheimer's disease and dementia in general, but also in first episode, late-life depression accompanied by subtle cognitive impairment (possibly organic depression). However, the results indicated that epsilon 4 allele frequency is related to (family history of) dementia and cognitive impairment, but not to possibly organic depression. The main predictor of late-life depression is an episode of psychiatric problems before the age of 65 years.
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PMID:Apolipoprotein E phenotype is not related to late-life depression in a population-based sample. 944 41

Mental dysfunction including cognitive, behavioural changes, mood disorders, and psychosis are increasingly recognized in patients with Parkinson's disease (PD) and related disorders. Their morphological correlates are complex due to multiple system degeneration. CNS changes contributing to cognitive changes in PD include 1. Dysfunction of subcorticocortical networks with neuron losses in a) the dopaminergic nigrostriatal loop, causing striato-(pre)frontal deafferentation and mesocortico-limbic system (medial substantia nigra, ventral tegmentum); b) noradrenergic (locus coeruleus), and serotonergic systems (dorsal raphe nuclei), c) cholinergic forebrain system (nucleus basalis of Meynert, etc), and d) specific nuclei of amygdala and limbic system (thalamic nuclei, hippocampus); 2. Limbic and/or cortical Lewy body and Alzheimer type pathologies with loss of neurons and synapses, 3. Combination of subcortical, cortical, and other pathologies. In general, degeneration of subcortical and striato-frontal networks causes cognitive, executive, behavioural, and mood disorders but less severe dementia than cortical changes which, when present in sufficient numbers, are important factors for overt dementia. In PD, cortical tau pathology with similar or differential patterns than in Alzheimer disease (AD) shows significant linear correlation with cognitive decline. In dementia with Lewy bodies (DLB), the second most frequent cause of dementia in the elderly, cortical Lewy bodies (LB) may or may not be associated with amyloid plaques and neuritic AD lesions. They predominantly affect the limbic system with less frequent isocortical Braak stages, whereas the cholinergic forebrain system is more severely affected than in AD. Both neuritic degeneration in limbic system in PD and DLB and the density of cortical synapse markers correlate with neuritic AD pathology and less with cortical LB counts. Apolipoprotein E epsilon4 allele frequency may represent a common genetic background for both AD and LB pathologies but there are different proportions of plaques between DLB (less Abeta1-40) and AD (more frequent Abeta1-40). Familial parkinsonism with dementia, linked to chromosome 17 (frontotemporal dementia with Parkinsonism (FTDP-17), and other tauopathies pathologically resembling PD plus AD, are often related to mutations of the tau gene, whereas familial PD with alpha-synuclein and Parkin mutations usually show no cognitive impairment. Mood disorders, in particular depression, and psychotic complications in both PD and DLB are related to complex involvement of noradrenergic and serotonergic systems, not confirmed in AD with depression, and both the prefrontal and limbic dopaminergic systems. The specific contributions of cortical and subcortical pathologies to mental dysfunction in PD and related disorders, their relationship to AD, and their genetic and aetiological backgrounds await further elucidation.
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PMID:Morphological substrates of mental dysfunction in Lewy body disease: an update. 1096 31

With an unprecedented demographic change in the world population, the prevention and effective treatment of age-dependent diseased has become a compelling need. Epidemiology contributes in this way by estimating the incidence and prevalence of specific categories of morbidity and by identifying the risk or protective factors of dementia. An integrative analysis of 47 surveys across 17 countries has suggested approximate rates under 1% for dementia from any cause in persons aged 60 to 69 years, rising to about 39% in persons 90 to 95 years old. The prevalence doubles with every five years of age within that range, with few differences taking into account secular changes, age, gender, place of living... Risks factors of vascular dementia are well known. Worldwide epidemiological surveys allow to differentiate "confirmed risk factors" of Alzheimer's type dementia (age, family history, Apolipoprotein E epsilon 4 genotype and Down's syndrome), "possible risk factors" (head injury, aluminum, previous depression...) and "protective factors" (education, anti-inflammatory drugs and estrogen replacement...).
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PMID:Epidemiology of dementia. 1149 May 44

Apolipoprotein E (ApoE) phenotyping was determined in 42 subjects with Alzheimer's disease (AD), 49 with depression, including 26 with early-onset depression (EOD) and 23 with late-onset depression (LOD), and 49 controls. In the EOD group, the frequency of the ApoE epsilon4 allele was not different from the control frequency (p = 0.532) but was significantly lower than in AD (p < 0.001). In the LOD group, the ApoE epsilon4 frequency was significantly higher than in the controls (p = 0.034) but was not different from that in the AD group (p = 0.229). Individuals with ApoE epsilon4 were at greater risk of getting AD (odds ratio, OR = 5.5, 95% confidence interval, CI, 2.0-14.0) or LOD (OR = 6.1, 95% CI, 1.9-19.0) than of EOD (OR = 0.7, 95% CI, 0.2-2.5). These results suggest an association between the ApoE epsilon4 allele frequency and LOD. Patients with LOD could be at risk of developing AD by an epsilon4-dependent pathway.
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PMID:Association of the apolipoprotein E epsilon4 allele with late-onset depression. 1168 4

Sleep-disordered breathing (SDB) is widely underdiagnosed among adults. However, SDB may be considered as a public health problem because of clinical consequences for the patient: impaired awake performance, increased risk factor for cardiovascular diseases and increased prevalence of depression. Apolipoprotein E (apoE), a protein involved in lipid metabolism, has 3 major alleles e2, e3 and e4. Recently, it has been shown that apoE e4 allele, a well-known risk factor for cardiovascular diseases, was also associated with SDB. In this study, we assessed a potential interaction between SDB, depression and apoE phenotype. 92 male patients (36-79 years old, mean age 58.0 11.2) consulting in hospital for SDB were enrolled in the study. Each patient had the following exams: 1) overnight polysomnography to determine apnea/hypopnea index (AHI=average number of respiratory events 10 seconds with no breathing per hour). A moderate-to-severe SDB was defined with AHI 15. 2) a psychiatric examination to look for previous or present symptoms of depressive illness. 3) blood sampling to determine apoE genotype (using PCR-RFLP method). In our study, allele frequencies for apoE e2, e3 and e4 were similar to those reported in general population. Among 92 patients, 68 (74%) presented moderate-to-severe SDB and 28 (30%) previous or present symptoms of depressive illness. Our results indicate that: 1) apoE e4 was significantly associated with moderate-to-severe SDB (n=92, p=0.03), 2) scores of apnea-hypopnea index were significantly higher in e4-positive versus e4-negative participants (n=57, p=0,05) and 3) ApoE and depression were not linked. This study confirms a potential interaction between SDB and apoE phenotype, as recently reported. This suggests that e4 allele might be a genetic risk factor for SDB (e4 allele frequency higher in patients with moderate-to-severe SDB versus general population) and/or consequently a deleterious factor for this pathology (increased AHI in e4-positive versus e4-negative patients). Depression might be only one of clinical consequences of SDB. Thus, SDB leads to repeated hypoxemia and numerous awakenings resulting in fatigue and decreased cognitive abilities suitable to the onset of depressive illness in vulnerable persons.
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PMID:[Is there an interaction between sleep-disordered breathing, depression and apolipoprotein E phenotype?]. 1553 11

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE epsilon4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.
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PMID:Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression. 1695 88

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.
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PMID:No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease. 1718 48

Late-onset depression (LOD) could be a very early manifestation of Alzheimer's disease (AD), although contradictory results have been reported. Cerebrovascular disease (CVD) may favor the development of LOD, and that the particular forms of vascular depression should be individualized. The Apolipoprotein E (ApoE) epsilon4 allele was shown to be a risk factor for AD. Its role in LOD is controversial, while it is still unknown in vascular depression. Our objective was to clarify the relationship between ApoE epsilon4 allele and LOD in patients with and without CVD. We examined the ApoE phenotypes in a sample of 311 subjects: 50 with vascular LOD, 24 with LOD without CVD, 115 with AD and 122 normal controls (NC). The study of the ApoE epsilon4 allele frequency showed significant differences between: AD group and the vascular LOD and NC groups; LOD group without CVD compared with NC group (p<0.05 to 0.001). The frequency of the epsilon4 allele in the LOD group without CVD did not differ significantly from the AD group, similarly the frequency of the epsilon4 allele in the vascular LOD group was not different from that in NC. The study suggests an association between the ApoE epsilon4 allele and the LOD without CVD. These patients could be at risk of developing AD by an epsilon4-dependent pathway. In contrast, the results show no association between the presence of ApoE epsilon4 allele and vascular depression and provide further evidence in support of the concept that ApoE epsilon4 allele is not associated with clinical CVD.
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PMID:Apolipoprotein E epsilon4 allele frequency in elderly depressed patients with and without cerebrovascular disease. 1733 10

We investigated the conversion rate and the risk factors for conversion to dementia from questionable dementia in 124 ethnic Chinese subjects with questionable dementia at a memory clinic of a university hospital. They were evaluated annually based on cognitive testing, the clinical dementia rating scale, and a psychiatrist's interview for depression and anxiety. Apolipoprotein E genotyping was performed on 111 of these questionable dementia subjects. All subjects were evaluated at least twice during the follow-up period of 20.4 +/- 12.4 months. During that period, 42 questionable dementia subjects were diagnosed as having Alzheimer's disease, with an annual conversion rate to dementia of 19.9%. Compared with the 82 nonconverters, the 42 converters were significantly older, had lower cognitive, depression, and anxiety scores, and a higher frequency of the apolipoprotein E epsilon4 allele. Cox regression analysis revealed that the Alzheimer's disease converters had lower scores for orientation, short-term memory, and anxiety, and a higher frequency of the apolipoprotein E epsilon4 allele than the nonconverters.
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PMID:Conversion to dementia from questionable dementia in an ethnic Chinese population. 1754 76


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